The Final Program

The Final Program for this Symposium was modified from that presented in the Book of Abstracts mainly due to the unforeseen incidence of the coronavirus in late January, 2020. We are grateful to the distinguished scientists who were able to take the place of those who were unable to come, and we regretted the absence of the distinguished scientists who had planned until the last hours to be with us. The SCHEDULE that is posted on this web site is the Final Schedule. That which is in the Book of Abstracts is the schedule that was expected to be the final schedule two weeks prior to the event. Strongly Donating 1,2,3-Triazole-Derived for Metal-Mediated Catalysis

Simone Bertini, Matteo Planchestainer, Francesca Paradisi, Martin Albrecht Department of Chemistry & Biochemistry, University of Bern, CH-3012 Bern, Switzerland [email protected]

Triazole-derived N-heterocyclic carbenes have become an attractive addition to the family of NHC ligands, in parts because their versatile and -tolerant synthesis through click- chemistry,1 and in other parts because of their stronger donor properties to transition metals when compared to ubiquitous Arduengo-type carbenes.2. We have been particularly attracted recently by the high robustness of these ligands towards oxidative and reductive conditions, which provides appealing opportunities for challenging redox catalysis. We have exploited these properties for example for developing iridium complexes as highly active and molecular oxidation catalysts.3 Here we will present our efforts to use triazole-derived carbenes to enable 1st row transition metals as catalytically competent entities. Incorporation of additional (hard) donor sites is benefical for this purpose and is greatly facilitated by the insensitivity of the click reaction to such functionalities. Here we will discuss new advances in redox catalysis including CO2 and proton reduction with first row transition metals systems. Moreover, we have expanded this carbene bonding to natural systems involved in redox processes.4

References 1. Kolb, H. C.; Finn, M. G.; Sharpless, K. B. Click Chemistry: Diverse Chemical Function from a Few Good Reactions. Angew. Chem. Int. Ed. 2001, 40 (11), 2004–2021. 2. Vivancos, Á.; Segarra, C.; Albrecht, M. “Mesoionic and Related Less Heteroatom-Stabilized N-Heterocyclic Carbene Complexes: Synthesis, Catalysis, and Other Applications” Chem. Rev. 2018, 118, 9493–9586. 3. Woods, J. A.; Lalrempuia, R.; Petronilho, A.; McDaniel, N. D.; Müller-Bunz, H.; Albrecht, M.; Bernhard, S. Carbene Iridium Complexes for Efficient Water Oxidation: Scope and Mechanistic Insights. Energy Environ. Sci. 2014, 7, 2316–2328. 4. Planchestainer, M.; Ségaud, N.; Shanmugam, M.; McMaster, J.; Paradisi, F.; Albrecht, M. “Carbene in Cupredoxin Protein Scaffolds: Replacement of a Histidine Ligand in the Active Site Substantially Alters Copper Redox Properties” Angew. Chem. Int. Ed. 2018, 57, 10677– 10682

1 Martin Albrecht

Department of Chemistry & Biochemistry, University of Bern Freiestrasse 3 3012 Bern, Switzerland

Email: [email protected] Web: http://albrecht.dcb.unibe.ch Twitter @albrecht_lab

Education 2002 – 2003 Postdoctoral Researcher Ciba SC, Basel (CH), within R&D Coating Effects 2001 –2002 Postdoctoral Research Associate, Yale University (USA) with Prof. R. H. Crabtree 1996 – 2000 Ph.D Utrecht University (NL) with Prof. G. van Koten 1991 – 1996 M.Sc. in Chemistry, University of Bern (CH); thesis work with T. R. Ward / A. Ludi

Positions 2015 – present Full Professor of Inorganic Chemistry, University of Bern (Switzerland) 2013 – 2015 Vice-Principal of Research and Innovation, UCD Faculty of Science 2009 – 2015 Full Professor of Inorganic Chemistry, University College Dublin (Ireland) 2003 – 2009 Alfred Werner Assistant Professor, University of Fribourg (CH), Principal Investigator

Awards & Invitations 2017 GIAN fellow (Indian Minstery of Human Resource Development) 2015 CATSA Eminent Visitor Award (Catalysis Society of South Africa) 2014 ERC Consolidator Grant 2013 Humboldt Fellow (Friedrich Wilhelm Bessel Research Award of A.v.H. Foundation) 2011 Fellow of the Royal Society of Chemistry (FRSC) 2008 Visiting Professor University of Otago (New Zealand) 2007 ERC starting grant 2003 Alfred Werner Assistant Professorship 2001 Backer prize of the KNCV (Royal Dutch Chemical Society)

Research Interests Ligand design, homogeneous catalysis, N-heterocyclic carbene metal complexes, redox catalysis, mesoionic C- and N-donor ligands, artificial metalloenzymes

Representative Publications 1,2,3-Triazolylidenes as Versatile Abnormal Carbene Ligands for Late Transition Metals P. Mathew, A. Neels, M. Albrecht, J. Am. Chem. Soc. 2008, 130, 13534–13535 Carbene in Cupredoxin Protein Scaffolds: Replacement of a Histidine Ligand in the Active Site Substantially Alters Copper Redox Properties M. Planchestainer, N. Ségaud, M. Shanmugam, J. McMaster, F. Paradisi, M. Albrecht, Angew. Chem. Int. Ed. 2018, 57, 10677–10682 NHC-based Iridium Catalysts for Hydrogenation and Dehydrogenation of N-Heteroarenes in Water under Mild Conditions A. Vivancos, M. Beller, M. Albrecht, ACS Catal. 2018, 8, 17–21 Mesoionic and Related Less Heteroatom-Stabilized N-Heterocyclic Carbene Complexes: Synthesis, Catalysis, and Other Applications A. Vivancos, C. Segarra, M. Albrecht, Chem. Rev. 2018, 118, 9493–9586.

2

Carbenes as powerful transition metal surrogates

Guy Bertrand UCSD-CNRS Joint Research Laboratory, Department of Chemistry, University of California, San Diego, La Jolla, California 92093-0358, USA [email protected]

It has been previously demonstrated that stable singlet electrophilic carbenes can behave as metal surrogates in the activation of small molecules and enthalpically strong E-H bonds,1 but it was believed that these activations only proceed through an irreversible activation barrier. We will show that, as it is the case with transition metals, the steric environment can be used to promote a reductive elimination at a carbon center.2

Along this line, we will show that stable bicyclic ()(amino)carbenes3 allow for the stoichiometric carbonylation of ortho-quinones, the catalytic version being hampered by the reaction of the carbene with the quinones. However, the use of a bulky cyclic (alkyl)(amino)carbenes4 avoids this quenching, and thus allows for the catalytic carbonylation reaction into the corresponding cyclic carbonates.5

H/D exchange at formyl groups is the most direct approach for the synthesis of deuterated . Until now, only platinum-group metal complexes were known to catalyze this transformation, with significant substrate scope limitations. We have found that mesoionic carbenes6 catalyze the H/D exchange of aryl, alkenyl and alkyl aldehydes in high yields and deuterium incorporation levels using deuterated as an affordable D source.7

References 1. Frey, G. D.; Lavallo, V.; Donnadieu, B.; Schoeller, W. W.; Bertrand, G. “Facile Splitting of and by Nucleophilic Activation at a Single Carbon Center.” Science 2007, 316, 439-441. 2. D. R. Tolentino, S. E. Neale, C. J. Isaac, S. A. Macgregor, M. K. Whittlesey, R. Jazzar, G. Bertrand, “Reductive Elimination at Carbon under Steric Control” J. Am. Chem. Soc. 2019, 141, 9823-9826. 3. Tomás-Mendivil, E.; Hansmann, M. M.; Weinstein, C. M.; Jazzar, R.; Melaimi, M.; Bertrand, G. “Bicyclic (Alkyl)(amino)carbenes (BICAACs): Stable Carbenes more Ambiphilic than CAACs” J. Am. Chem. Soc. 2017, 139, 7753-7756. 4. Melaimi, M.; Jazzar, R.; Soleilhavoup, M.; Bertrand, G. “Cyclic (Alkyl)(Amino)Carbenes (CAACs): Recent developments” Angew. Chem. Int. Ed. 2017, 56, 10046-10068. 5. Tomás-Mendivil, E.; Tolentino, D. R.; Peltier, J. R.; Jazzar, R.; Bertrand, G. unpublished 2019 6. Guisado-Barrios, G.; Soleilhavoup, M.; Bertrand, G. “1H‑1,2,3-Triazol-5-ylidenes: Readily Available Mesoionic Carbenes” Acc. Chem. Res. 2018, 51, 3236-3244. 7. Liu, W.; Zhao, L. L.; Melaimi, M.; Cao, L.; Xu, X.; Bouffard, J.; Bertrand, G.; Yan, X. unpublished 2019

3

CURRICULUM VITAE – Guy Bertrand

Professor of Chemistry Director of the UCSD-CNRS Joint Research Laboratory, Department of Chemistry, University of California, San Diego, La Jolla, California 92093- 0358, United States Tel: 001 (858) 534-5412 Email: [email protected] Homepage: http://bertrandgroup.ucsd.edu

Scientific Vita Since 2012 University of California San Diego, Distinguished Professor, Department of Chemistry and Biochemistry. 2002-2012 University of California Riverside, Distinguished Professor, Department of Chemistry. 1998-2005 Director of the Laboratoire d'Hétérochimie Fondamentale et Appliquée at the University Paul Sabatier (Toulouse, France) 1988-1998 Director of Research CNRS, Laboratoire de Chimie de Coordination (Toulouse, France)

Research Field Stabilization of highly reactive species, stable carbenes and their uses as ligands for transition metals, as organocatalysts, and in material sciences

Selected Awards and Recognition 2004 Member the French Academy of Sciences 2006 Fellow of the American Association for Advancement of Science 2010 Sir Ronald Nyholm Lectureship and Medal of the RSC 2010 Grand Prix Le Bel of the French Chemical Society 2013 Chevalier de la Legion d’Honneur 2014 ACS Award in Inorganic Chemistry 2015 Senior Humboldt Research Award, Reinvitation 2016 Sir Geoffrey Wilkinson Award of the RSC 2017 Sacconi Medal of the Italian Chemical Society 2018 Named “Distinguished Visiting Professor” at Tsinghua University (China) 2018 Named “Honorable Professor” at Wuhan University of Technology (China)

Representative Publications 1. R. Hamze, J. L. Peltier, D. Sylvinson, M. Jung, J. Cardenas, R. Haiges, M. Soleilhavoup, R. Jazzar, P. I. Djurovich, G. Bertrand, M. E. Thompson, “Eliminating nonradiative decayin Cu(I) emitters: >99% quantum efficiency and microsecond lifetime” Science 2019, 363, 601-606. 2. D. R. Tolentino, S. E. Neale, C. J. Isaac, S. A. Macgregor, M. K. Whittlesey, R. Jazzar, G. Bertrand, “Reductive Elimination at Carbon under Steric Control” J. Am. Chem. Soc. 2019, 141, 9823-9826. 3. V. Regnier, E. A. Romero, F. Molton, R. Jazzar, G. Bertrand,, D. Martin “What are the Radical Intermediates in Oxidative N-Heterocyclic Carbene Organocatalysis?” J. Am. Chem. Soc. 2019, 141, 1109-1117. 4. R. Nakano, R. Jazzar, G. Bertrand “A Crystalline Mono-Substituted Carbene” Nature Chem. 2018, 10, 1196-1200. 5. C. M. Weinstein, G. P. Junor, D. R. Tolentino, R. Jazzar, M. Melaimi, G. Bertrand “Highly Ambiphilic Room Temperature Stable Six-Membered Cyclic (Alkyl)(amino)carbenes” J. Am. Chem. Soc. 2018, 140, 9255-9260.

4 Journey into cyclopropane chemistry and continuous flow synthesis

André B. Charette Department of Chemistry, Université de Montréal, Montréal, Québec, Canada H3C 3J7 [email protected]

This presentation will highlight several aspects of our research program including new synthetic methods to generate functionalized cyclopropane derivatives.1 Several new substituted zinc carbenoid reagents will be prepared, characterized and tested in cyclopropanation reactions. In the second part of the talk, we will be focus on new flow methodologies. The continuous flow technology to avoid manipulation of potentially harmful reagents will be incorporated into new method development. The preparation of reagents that can served as useful zinc carbenoid reagents will be discussed along with their use in transition metal catalyzed processes.2,3 Finally, the functionalization of cyclopropane products via C–H and C–C functionalization reactions will be presented.

References

1. Taillemaud, S.; Diercxsens, N.; Gagnon, A.; Charette, A. B., Mechanism-Driven Elaboration of an Enantioselective Bromocyclopropanation Reaction of Allylic . Angew. Chem. Int. Ed. 2015, 54, 14108-14112. 2. Allouche, E. M. D.; Charette, A. B., Non-stabilized diazoalkane synthesis via the oxidation of free hydrazones by iodosylbenzene and application in in situ MIRC cyclopropanation. Chem Sci 2019, 10, 3802-3806. 3. Rulliere, P.; Benoit, G.; Allouche, E. M. D.; Charette, A. B., Safe and Facile Access to Nonstabilized Diazoalkanes Using Continuous Flow Technology. Angew. Chem. Int. Ed. 2018, 57, 5777-5782.

5

CURRICULUM VITAE – André B. Charette

Professor of Chemistry Head of Department of Chemistry Department of Chemistry, Université de Montréal, Montréal Québec, Canada H3C 3J7 Tel: (514) 343-2432 Email: [email protected] Homepage: https://charettelab.ca

Scientific Vita 2014-present Head, Department of Chemistry, Université de Montréal 2014-present Director, NSERC CREATE Program in Continuous Flow Science, Université de Montréal 2005-2019 Canada Research Chair in Stereoselective Synthesis of Bioactive Molecules, Université de Montréal 2000-2010 NSERC/Merck Frosst/Boehringer Ingelheim Industrial Chair, Université de Montréal Since 1998 Université de Montréal, Professor 1994-1998 Université de Montréal, Associate Professor 1992-1994 Université de Montréal, Assistant Professor, NSERC University Research Fellow 1989-1992 Université Laval, Assistant Professor, NSERC University Research Fellow

Research Field Asymmetric catalysis, cyclopropanation reactions, continuous flow synthesis, C–H and C–C bond activation of cyclopropanes, heterocyclic chemistry

Selected Awards and Recognition 1994 Eli Lilly GRantee Award 1996 Alfred P. Sloan Research Fellowship 2006 R.U. Lemierx Award, Canadian Society for Chemistry 2006 Urgel Archambault Award, Association franophone pour le savoir 2007 Fellow of the Royal Society of Canada: The Academies of Arts, Humanities and Sciences of Canada 2007 Arthur C. Cope Scholar Award, American Chemical Society 2008 Prix Marie-Victorin, Government of Québec 2009 Alfred Bader Award, Canadian Society for Chemistry 2015 Doctorate Honoris Causa, INSA de Rouen 2015 Labex Synorg Chair, Université de Rouen 2018 CIC Medal, Chemical Institute of Canada

Representative Publications 1. Allouche, E. M. D.; Charette, A. B. Non-stabilized Diazoalkanes Synthesis via the Oxidation of Free Hydrazones by Iodosylbenzene and Application to in situ MIRC Cyclopropanations Chemical Science 2019, 10, 3802-2806 . 2. Sayes, M.; Benoit, G.; Charette, A. B. Borocyclopropanation of Styrenes Mediated by UV-light Under Continuous Flow Conditions. Angew. Chem., Int. Ed. 2018, 56, 13514-13518. 3. Rullière, P.; Benoit, G.; Charette, A. B. Safe and Easy Access to Non-Stabilized Diazoalkanes Using Continuous Flow Technology. Angew. Chem., Int. Ed. 2018, 56, 5777-5783. 4. Allouche, E. M. D.; Taillemaud, S.; Charette, A. B. Spectroscopic Characterization of (Diiodomethyl)zinc Iodide: Application to the Stereoselective Synthesis and Functionalization of Iodocyclopropanes. Chem. Commun. 2017, 53, 9606-9609.

6

Catalyst-Controlled C-H Functionalization

Huw M. L. Davies Department of Chemistry, Emory University, Atlanta, GA, USA [email protected]

A toolbox of catalysts has been generated for site-selective functionalization of unactivated C–H bonds. Catalysts have been developed for selective functionalization of primary, secondary or tertiary C–H bonds[1-3] and can differentiate between similar secondary C–H bonds.[4,5] The application of these reactions to the synthesis of chiral scaffolds of pharmacutical interest will also be described.

Fundamental Studies on Site Selective Reactions

H CH3

H H H

H

Pharmaceutically Relevant Substrates PG H N H

Ar H n H H H R H with University of Regensburg R R Si H R H H R H n H H H H with AbbVie with AbbVie with Novartis

References 1. Site-selective and stereoselective functionalization of unactivated C-H bonds, Liao, K.; Negretti, S.; Musaev, D. G.; Bacsa, J.; Davies, H. M. L. Nature 2016, 533, 7602-7606. 2. Catalyst-Controlled Site-Selective and Stereoselective Functionalization of Non-Activated Tertiary C–H Bonds, Liao, K.; Pickle, T.; Boyarskikh, V.; Bacsa, J.; Musaev, D. G.; Davies, H. M. L., Nature 2017, 551, 609–613. 3. Design of Catalysts for Site-Selective and Enantioselective Functionalization of Non- Activated Primary C–H Bonds, Liao, K.; Yang, Y.; Li, Y.; Sanders, J.; Houk, K. N.; Musaev, D. G.; Davies, H. M. L. Nature Chem. 2018, 10, 1048–1055. 4. Catalyst-Controlled Selective Functionalization of Unactivated C–H Bonds in the Presence of Electronically Activated C–H Bonds, Wenbin Liu, Zhi Ren, Aaron T. Bosse, Kuangbiao Liao,, Elizabeth L. Goldstein, John Bacsa, Djamaladdin G. Musaev, Brian M. Stoltz and Huw M. L. Davies J. Am. Chem. Soc. 2018, 140, 12247–12255. 5. Desymmetrization of Cyclohexanes by Site-Selective and Stereoselective C-H Functionalization Jiantao Fu, Zhi Ren, John Bacsa, Djamaladdin G. Musaev & Huw M. L. Davies, Nature 2018, 564, 395-399.

7

CURRICULUM VITAE – Huw Davies

Professor of Chemistry Asa Griggs Candler Professor of Chemistry, Director of NSF Center for Selective C-H Functionalization, Emory University, 1515 Dickey Drive, Atlanta, GA 30024, USA Tel: 001 (404) 727-6839 Email: [email protected] Homepage: https://scholarblogs.emory.edu/davieslab/ CCHF Homepage: http://www.nsf-cchf.com/

Scientific Vita Since 2008 Emory University, Larkin Profssor of Chemistry. 1995-2008 State University of New York at Buffalo: Professor (1995) Distinguished Professor (2003), Larkin Professor of Chemistry (2003). 1983-1995 Wake Forest University: Assistant Professor (1983), Associate Professor (1988), Professor (1993).

Research Field Catalytic asymmetric C–H functionalization, new synthetic methodology based on carbenoid intermediates, design of chiral catalysts for asymmetric synthesis, total synthesis of biologically active natural products, development of enabling technology for the synthesis of pharmaceutically relevant targets.

Selected Awards and Recognition 2013-Present Associate Editor, Chemical Society Reviews 2005 Arthur C. Cope Scholar Award (American Chemical Society) 2013 eEROS Reagent of the Year Award, 2015 Fellow of the National Academy of Inventors 2017 Alexander von Humboldt Foundation Research Award 2018 Paul N. Rylander Award 2019 Herbert C. Brown Award for Creative Research in Synthetic Methods (American Chemical Society)

Representative Publications 1. Site-selective and stereoselective functionalization of unactivated C-H bonds, Liao, K.; Negretti, S.; Musaev, D. G.; Bacsa, J.; Davies, H. M. L. Nature 2016, 533, 7602-7606. 2. Catalyst-Controlled Site-Selective and Stereoselective Functionalization of Non-Activated Tertiary C–H Bonds, Liao, K.; Pickle, T.; Boyarskikh, V.; Bacsa, J.; Musaev, D. G.; Davies, H. M. L., Nature 2017, 551, 609–613. 3. Design of Catalysts for Site-Selective and Enantioselective Functionalization of Non-Activated Primary C–H Bonds, Liao, K.; Yang, Y.; Li, Y.; Sanders, J.; Houk, K. N.; Musaev, D. G.; Davies, H. M. L. Nature Chem. 2018, 10, 1048–1055. 4. Catalyst-Controlled Selective Functionalization of Unactivated C–H Bonds in the Presence of Electronically Activated C–H Bonds, Wenbin Liu, Zhi Ren, Aaron T. Bosse, Kuangbiao Liao,, Elizabeth L. Goldstein, John Bacsa, Djamaladdin G. Musaev, Brian M. Stoltz and Huw M. L. Davies J. Am. Chem. Soc. 2018, 140, 12247–12255. 5. Desymmetrization of Cyclohexanes by Site-Selective and Stereoselective C-H Functionalization Jiantao Fu, Zhi Ren, John Bacsa, Djamaladdin G. Musaev & Huw M. L. Davies, Nature 2018, 564, 395-399.

8 Metal Carbenes via Decarbenation

Antonio M. Echavarren Institute of Chemical Research of Catalonia (ICIQ), Barcelona Institute of Science and Technology, Av. Països Catalans 16, 43007 and Departament de Química Analítica i Química Orgànica, Universitat Rovira i Virgili, C/Marcel·li Domingo s/n, 43007 Tarragona, Spain [email protected]

The gold(I)-catalyzed decarbenation via a retro-Buchner reaction is a new method for the generation of gold(I) carbenes from readily available cycloheptatrienes.1 The resulting gold(I) carbenes react with alkenes to form cyclopropanes and take part in other inter- and intramolecular transformations.2 Interestingly, more reactive trimethylcycloheptatrienes undergo gold(I) and Zn(II)-catalyzed decarbenation at very mild conditions.3

R 1 1 R 2 R R R2 Me Me R cyclopentenes indenes cyclopentadienes (3+2) indanes (4+1) 1 C Ph R Ph S O 2 O aldehydes intramolecular R2 reactivity H

R3Si Ph fluorenes electrophilic R3Si–H metal carbenes allylsilanes R R [M] (catalyst) R [M] R R Ph R Ph –Arene [Zn] cyclopropanes cycloheptatriene norcaradiene [M] = [Au] [Rh]

The retro-Buchner reaction also takes place with [Rh(TFA)2]2 as the catalyst to generate donor- substituted Rh(II) carbenes, which undergo cyclopropanation reactions, react with silanes to give allyl silanes by intermolecular Si–H insertion and give aldehydes by mild oxidations, which allowed developing a method for the iterative vinylogation of aldehydes.4

References 1. (a) Solorio-Alvarado, C. R.; Echavarren, A. M. “Gold-Catalyzed Annulation/Fragmentation: Formation of Free Gold Carbenes by Retro-Cyclopropanation”, J. Am. Chem. Soc. 2010, 132, 11881–11883. (b) Solorio-Alvarado, C. R.; Wang, Y.; Echavarren, A. M. “Cyclopropanation with Gold(I) Carbenes by Retro-Buchner Reaction from Cycloheptatrienes”, J. Am. Chem. Soc. 2011, 133, 11952–11955M. (c) Herlé, B.; Holstein, P. M.; Echavarren, A. M. “Stereoselective Cis-Vinylcyclopropanation via Gold(I)-Catalyzed Retro-Buchner Reaction under Mild Conditions”, ACS Catal. 2017, 7, 3668–3675. 2. (a) Wang, Y.; McGonigal, P. R.; Herlé, B.; Besora, M.; Echavarren, A. M. “Gold(I) Carbenes by Retro-Buchner Reaction: Generation and Fate”, J. Am. Chem. Soc. 2014, 136, 801–809. (b) Wang, Y.; Muratore, M. E.; Rhong, Z.; Echavarren, A. M. “Formal (4+1) Cycloaddition of Methylencyclopropanes with 7-aryl-1,3,5-cycloheptatrienes via Triple Gold(I)-Catalysis”, Angew. Chem. Int. Ed. 2014, 53, 14022–14026. (c) Yin, X.; Mato, M.; Echavarren, A. M. “Gold(I)-Catalyzed Synthesis of Indenes and Cyclopentadienes: Access to (±)- Laurokamurene B and the Skeletons of Cycloaurenones and Dysiherbols”, Angew. Chem. Int. Ed. 2017, 56, 14591–14595; 3. Mato, M.; Herlé, B.; Echavarren, A. M. “Cyclopropanation by Gold or Zinc-Catalyzed Retro-Buchner Reaction at Room Temperature”, Org. Lett. 2018, 20, 4341–4345. 4. Mato, M.; Echavarren, A. M. “Donor Carbenes by Retro-Buchner Reaction”, Angew. Chem. Int. Ed. 2019, 58, 2088–2092.

9 CURRICULUM VITAE – Antonio M. Echavarren

Professor of Organic Chemistry and ICIQ Group Leader Institute of Chemical Research of Catalonia (ICIQ), Tarragona 43007, Spain Email: [email protected] Homepage: http://www.iciq.org/research/research_group/prof-antonio- m-echavarren/

Scientific Vita Since 2004 Institute of Chemical Research of Catalonia (ICIQ). Since 2009 Rovira i Virgili University, Professor, Department of Organic and Analytical Chemistry, Tarragona, Spain. Since 2005 Research Professor, CSIC. 1992-2009 Autonomous University of Madrid, Professor, Department of Organic Chemistry, Madrid, Spain. 1998-1992 Researcher, Institute of Organic Chemistry, CSIC, Madrid. 1986-1998 NATO Fellow, Colorado State University. 1984-1986 Autonomous University of Madrid, Assistant Professor, Department of Organic Chemistry, Madrid, Spain.

Research Field Synthetic methodology, total synthesis, gold catalysis, metal-catalyzed C-H functionalization, metal carbene chemistry, polyarene synthesis

Selected Awards and Recognition 2004 Janssen-Cilag Organic Chemistry Award of the Spanish Royal Society of Chemistry (RSEQ). 2010 Gold Medal of the Spanish Royal Society of Chemistry (RSEQ). 2012 Fellow, Royal Society of Chemistry. 2015 Arthur C. Cope Senior Scholar Award (American Chemical Society). 2017 Kurt Alder Lectureship 2018 President Spanish Royal Society of Chemistry

Representative Publications 1. de Orbe, M. E.; Amenós, L.; Kirillova, M. S.; Wang, Y.; López-Carrillo, V.; Maseras, F.; Echavarren, A. M. “Cyclobutene vs. 1,3-Diene Formation in the Gold-Catalyzed Reaction of with Alkenes: The Complete Mechanistic Picture” J. Am. Chem. Soc. 2017, 139, 10302– 10311. 2. García-Morales, C.; Ranieri, B.; Escofet, I.; López-Suarez, L.; Obradors, C.; Konovalov, A. I.; Echavarren, A. M. “Enantioselective Synthesis of Cyclobutenes by Intermolecular [2+2] Cycloaddition with Non-C2 Symmetric Digold Catalysts” J. Am. Chem. Soc. 2017, 139, 13628– 13631. 3. García-Morales, C.; Pei, X.; Sarria Toro, J. M.; Echavarren, A. M. “Direct Observation of Aryl Gold(I) Carbenes that Undergo Cyclopropanation, C-H Insertion, and Dimerization Reactions” Angew. Chem. Int. Ed. 2019, 58, 3957–3961. 4. Mato, M.; Echavarren, A. M. “Donor Rhodium Carbenes by Retro-Buchner Reaction“ Angew. Chem. Int. Ed. 2019, 58, 2088–2092.

10 Chiral N,N'-Dioxide-Metal Complexes Catalyzed Reactions of α-Diazo Carbonyl Compounds

Xiaoming Feng College of Chemistry, Sichuan University, Chengdu 610064, China [email protected]

Chiral N,N′-dioxide-amines represent a kind of privileged ligand, which could coordinate with a number of metal salts to form chiral metal complex catalysts for asymmetric reactions. We found that chiral N,N′-dioxide- scandium complexes enable a various nucleophilic addition-initiated reactions of α-diazoesters, such as Roskamp reaction with aldehydes, ring-expansion reaction of isatins, intramolecular homologation of ketones, C-H insertion and cyclopropanation of α,β-unsaturated ketones. Recently, we also established an unexpected homologation/dyotropic rearrangement/interconversion/[3+2] cycloaddition cascade reaction of α-diazoester- terminated N-propyl-substituted isatin derivatives, which allows rapid construction of several classes of dimeric 1 polycyclic compounds. Chiral N,N'-dioxide-Sc(OTf)3 catalyzed asymmetric α-amination with ketones represented an exception. We also expanded chiral N,N′-dioxide-metal complexes into dimetallic relay catalysis, including three-component [3+2] cycloaddition to construct tetrahydroindolizines,2 and N-H insertion/Michael addition of α-diazoketones to synthesize trisubstituted indolines. In addition, we designed a new type of α-diazo compounds by introducing pyrazoleamide as the electron-withdrawing group. The unique examples of asymmetric Doyle-Kirmse reaction,3 [2,3]-Stevens and Sommelet–Hauser rearrangements of sulfonium ylides generated in situ from -diazo pyrazoleamides and sulfides were realized. The pyrazoleamide substituent of the α-diazo compounds serves as both an activating and a directing group for the readily formation of metal-carbene and Lewis-acid bonded ylide intermediate in the assistant of dual tasking nickel(II) complex.

References 1. Tan, F.; Liu, X. H.; Wang, Y.; Dong, S. X.; Yu, H.; Feng, X. M. “Chiral Lewis Acid Catalyzed Reactions of a-Diazoester Derivatives: Construction of Dimeric Polycyclic Compounds” Angew. Chem. Int. Ed. 2018, 57, 16176. 2. Zhang, D.; Lin, L. L.; Yang, J.; Liu, X. H.; Feng, X. M. “Asymmetric Synthesis of Tetrahydroindolizines by Bimetallic Relay Catalyzed Cycloaddition of Pyridinium Ylides” Angew. Chem. Int. Ed. 2018, 57, 12323. 3. Lin, X. B.; Tang, Y.; Yang, W.; Tan, F.; Lin, L. L.; Liu, X. H.; Feng, X. M. “Chiral Nickel(II) Complex Catalyzed Enantioselective Doyle-Kirmse Reaction of α-Diazo Pyrazoleamides” J. Am. Chem. Soc. 2018, 140, 3299.

11

CURRICULUM VITAE – Xiaoming Feng

Professor of Chemistry College of Chemistry, Sichuan University, Chengdu 610064, China Tel: 86 (28) 8541-8249 Email: [email protected] Homepage: http://chem.scu.edu.cn/chem-asl/

Scientific Vita Since 2000 Professor, College of Chemistry, Sichuan University, Chengdu, China 1997-2000 Professor, Chengdu Institute of Organic Chemistry, CAS, China 1993-1996 PhD in Organic Chemistry, with Prof. Zhitang Huang & Yaozhong Jiang, Institute of Chemistry, CAS 1988-1993 Assistant & associate professor, Southwest Normal University, China 1985-1988 MS in organic chemistry, with Prof. Ziyi Zhang, Lanzhou University, China 1981-1985 BS in chemistry, Lanzhou University, China

Research Field synthetic methodology, asymmetric synthesis, organometallic chemistry

Selected Awards and Recognition 2002 the National Science Fund for Distinguished Young Scholars (China) 2005 the Special Professor of the Chang Jiang Scholars by the Ministry of Education of China 2009 Higher Education Outstanding Scientific Research Output Awards (Science and Technology) from the Ministry of Education (First class, China) 2011 SciFinder Award for Creative Work in Synthetic Organic Chemistry, CCS 2012 the State Natural Science Award, P.R. China (Second class, China) 2013 a Chinese Academy of Sciences Academician 2016 Chiral Chemistry Award, CCS 2018 the 2018 Future Science Prize in Physical Sciences, China

Representative Publications 1. Liu, X. H.; Dong, S. X.; Lin, L. L.; Feng, X. M., Chiral Amino Acids-Derived Catalysts and Ligands, Chin. J. Chem. 2018, 36, 791−797. 2. Liu, X. H.; Zheng, H. F.; Xia, Y.; Lin, L. L.; Feng, X. M., Asymmetric Cycloaddition and Cyclization Reactions Catalyzed by Chiral N,N′-Dioxide-Metal Complexes. Acc. Chem. Res. 2017, 50, 2621-2631. 3. Liu, X. H.; Lin, L. L.; Feng, X. M., Chiral N,N-Dioxides: New Ligands and Organocatalysts for Catalytic Asymmetric Reactions, Acc. Chem. Res. 2011, 44, 574–587. 4. Lin, X. B.; Tang, Y.; Yang, W.; Tan, F.; Lin, L. L.; Liu, X. H.; Feng, X. M., Chiral Nickel(II) Complex Catalyzed Enantioselective Doyle-Kirmse Reaction of α-Diazo Pyrazoleamides, J. Am. Chem. Soc. 2018, 140, 3299–3305. 5. Zhang, D.; Lin, L. L.; Yang, J.; Liu, X. H.; Feng, X. M., Asymmetric Synthesis of Tetrahydroindolizines by Bimetallic Relay Catalyzed Cycloaddition of Pyridinium Ylides, Angew. Chem. Int. Ed. 2018, 57, 12323–12327.

12 Heterobimetallic Complexes from Asymmetric Bis-NHC Precursors

F. Ekkehardt Hahn Institut für Anorganische und Analytische Chemie, Westfälische Wilhelms-Univerität Münster, Corrensstrasse 30, 48149 Münster, Germany [email protected]

The combination of a neutral 2-halogenoazole with cationic imidazolium group leads to compounds which allow the preparation of heterobimetallic complexes through the site selective metalation of the two different NHC precursors. Neutral 2-halogenoazoles, for example, react with complexes of low- valent transition metals in an oxidative addition reaction to give azolato complexes featuring an unsubstituted azolato ring-nitrogen atom. Protonation or alkylation of this ring-nitrogen atom is possible.1 Alternatively, N,N’- dialkylated azolium cations can be deprotonated at the C2-position to give free NHCs which react with complexes containing oxidized metal centers to give complexes with conventional NR,N’R-NHC ligands.2 The asymmetric bis-NHC precursor H-1(PF6) reacts with Ag2O followed by transmetallation of the NHC ligand to AuI to give the Au-imidazolylidene complex. The 2- chlorobenzimidazole group does not participate in this reaction. Subsequently, the C2‒Cl bond can add 0 oxidatively to Pd to give [2](PF6). The alternative reaction sequence, oxidative addition of the C2‒Cl bond of the 2-chlorobenzimidazole moiety followed by deprotonation/metallation of the imidazolium group leads to the same type of complex.3 The reaction of H-1(PF6) with [Pt(PPh3)4] yields complex [3](PF6), most likely via a Domino- reaction comprising oxidative addition of the C‒Cl bond, intramolecular H-shift of the imidazolium proton to the benzimidazolate and coordination of the generated NHC to the platinum atom. The synthetic potential of unsymmetrical bis-NHC precursors will be discussed.

References 1. Kuwata, S.; Hahn, F. E. “Complexes Bearing Protic N-Heterocyclic Carbene Ligands” Chem. Rev. 2018, 118, 9642−9677. 2. Hahn, F. E.; Jahnke, M. C. “Heterocyclic Carbenes: Synthesis and Coordination Chemistry” Angew. Chem. Int. Ed. 2008, 47, 31223172. 3. Bente, S.; Kampert, F.; Tan, T. T. Y.; Hahn, F. E. “Site-selective metallation of dicarbene precursors” Chem. Commun. 2018, 54, 1288712890.

13

CURRICULUM VITAE – F. Ekkehardt Hahn

Professor of Chemistry Department of Inorganic Chemistry Westfälische Wilhelms-Universität Münster Corrensstrasse 30, 48149 Münster, Germany Tel: 0049 (151) 833-3111 Email: [email protected] Homepage: https://www.uni-muenster.de/Chemie.ac/hahn/index.html

Scientific Vita since 1998 Westfälische Wilhelms-Universität Münster, Professor of Chemistry 19911998 Freie Universität Berlin, Associate Professor of Chemistry 19881991 Technische Universität Berlin, Assistant Professor

Research Field Metal carbene (NHC) chemistry, isocyanide complexes, post-synthetic modifications on NHC and isocyanide complexes, template syntheses, synthetic methodology

Selected Awards and Recognition 2008 Fellow, Royal Society of Chemistry 2009 Julius von Haast Fellowship, New Zealand Ministry of Research Science and Technology 2014 JSPS Fellowship 2018 Guest Editor Chem. Rev. (themed issue on N-heterocyclic carbenes) 2019 Thousand Talents Professor, PR China Ministry of Education Guest Professorships National University of Singapore (2002), University of Auckland (2009), Taiwan National University (2011), Ben Gurion University of the Negev (2012), University of Tasmania (2015), Federal University of Minas Gerais, Belo Horizonte (2019). Concurrent Professor at Fudan University, Shanghai (20152018) and at Northwest University Xi’an, China (20182023).

Representative Publications 1. Kösterke, T.; Pape, T.; Hahn, F. E. “Synthesis of NHC Complexes by Oxidative Addition of 2-Chloro- N-methylbenzimidazole” J. Am. Chem. Soc. 2011, 133, 2112−2115. 2. Conrady, F. M.; Fröhlich, R.; Schulte to Brinke, C.; Pape, T.; Hahn, F. E. “Stepwise Formation of a Molecular Square with Bridging NH,O-Substituted Dicarbene Building Blocks” J. Am. Chem. Soc. 2011, 133, 11496−11499. 3. Brackemeyer, D.; Hervé, A.; Schulte to Brinke, C.; Jahnke, M. C.; Hahn, F. E. “A Versatile Methodology for the Regioselective C8-Metalation of Purine Bases“ J. Am. Chem. Soc. 2014, 136, 7841−7844. 4. Sun, L.-Y.; Sinha, N.; Yan, T.; Wang, Y.-S.; Tan, T. T. Y.; Yu, L.; Han, Y.-F.; Hahn, F. E. “Template Synthesis of Three-Dimensional Hexakisimidazolium Cages” Angew. Chem. Int. Ed. 2018, 57, 51615165. 5. Sinha, N.; Hahn, F. E. “Metallosupramolecular Architectures Obtained from Poly-N-heterocyclic Carbene Ligands” Acc. Chem. Res. 2017, 50, 2167−2184. 6. Kuwata, S.; Hahn, F. E. “Complexes Bearing Protic N-Heterocyclic Carbene Ligands” Chem. Rev. 2018, 118, 9642−9677.

14 Electrophilic Trapping of Reactive Intermediates from Metal Carbenes: Umpolung of Reactivities

Wenhao Hu School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China [email protected]

Metal carbenes are versatile intermediates that enable novel synthetic pathways. These divalent carbon species exhibit either electrophilic or nucleophilic character, depending on the carbene and metal fragments. For example, the ruthenium carbenes in metathesis reactions are nucleophilic, while transition metal-catalyzed decomposition of diazo compounds produces the normally electrophilic metal carbenes. Although the metal carbene reactivity is regulated by the metal, the umpolung of carbene reactivity by changing metal remains challenging. Cyclopropene is an ideal precursor for vinyl carbene. The rhodium-catalysed ring-opening of cyclopropenes will lead to electrophilic vinyl rhodium carbenes (path a). Nucleophilic attack to these species by tethered oxygen atom will generate reactive oxonium/carbonyl ylides, which could be trapped by electrophiles1-2 to give O-containing heterocycles, such as dihydrofurans and butenolides. Interestingly, the structures of ylides greatly influence the regioselectivity of nucleophilic addition, in which carbonyl ylide react at the original carbenic center, while the oxonium ylide will undergo electrophilic addition to the vinylogous site.3

When using zinc halide as the promotors,3 the cyclopropene will convert into a zinc carbenoid. This species shows a nucleophilic character and undergoes nucleophilic attack to electrophiles without elimination of the halogen atom, delivering products containing a synthetically valuable alkenyl halide moiety. This controllable metal-induced de novo umpolung of carbene reactivity presents an efficient approach for chemodivergent synthesis.

References 1. Guo, X.; Hu, W. “Novel Multicomponent Reactions via Trapping of Protic Onium Ylides with Electrophiles”. Acc. Chem. Res. 2013, 46, 2427−2440. 2. Kang, Z.; Wang, Y.; Zhang, D.; Wu, R.; Xu, X.; Hu, W. “Asymmetric counter-anion- directed aminomethylation: synthesis of chiral β‑ amino acids via trapping of an enol intermediate”. J. Am. Chem. Soc. 2019, 141, 1473−1478. 3. Zhang, D.; Kang, Z.; Liu, J.; Hu, W. “Metal-Dependent Umpolung Reactivity of Carbenes Derived from Cyclopropenes.” iScience 2019, 14, 292–300.

15

CURRICULUM VITAE – Wenhao Hu

Professor of Medicinal Chemistry Chang Jiang Scholar Distinguished Professor, Dean of School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China Tel: 86-13632226060/86-20-39943116 Email: [email protected]

Scientific Vita Since 2016 Dean and Professor, School of Pharmaceutical Sciences, Sun Yat-sen University 2006-2016 Professor, Department of Chemistry, East China Normal University; Chair, Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development (2011-2016). 2003-2006 Research Investigator (II), Process Chemistry, Bristol-Myers Squibb Co. 2002-2003 Staff Scientist, Medicinal Chemistry, GeneSoft Pharmaceutical Inc. 1998-2002 Postdoctoral Research Associate, University of Arizona. Advisor: Prof. Michael P. Doyle

Research Field Multicomponent reactions, metal carbene chemistry, diazo chemistry, trapping of transient intermediates, asymmetric catalysis, medicinal chemistry

Selected Awards and Recognition 2001 CAS Hundred Talents Award (Chinese Academia of Science) 2005 BMS Star Award (Bristol Myers Squibb Company) 2006 Shuguang Scholar Award (Shanghai) 2007 Pujiang Program Award (Shanghai) 2009 Excellent Academic Leaders of Shanghai 2009 Oriental Scholar Award (Shanghai) 2010 Asian Core Program Lectureship Award 2010 The Second Prize of Natural Science Award from Chinese Ministry of Education 2011 Asian Core Program Lectureship Award 2015 National Key Talent Project 2016 State Council Expert for Special Allowance 2016 The First Prize of Natural Science Award from Shanghai Municipality

Representative Publications 1. Kang, Z.; Wang, Y.; Zhang, D.; Wu, R.; Xu, X.; Hu, W. “Asymmetric counter-anion-directed aminomethylation: synthesis of chiral β‑ amino acids via trapping of an enol intermediate”. J. Am. Chem. Soc. 2019, 141, 1473−1478. 2. Liu, S.; Yao, W.; Liu, Y.; Wei, Q.; Chen, J.; Wu, X.; Xia, F.; Hu, W. “A Rh(II)-catalyzed multicomponent reaction by trapping an a-amino enol intermediate in a traditional two-component reaction pathway”. Sci. Adv. 2017, 3: e1602467. 3. Zhang, D.; Zhou, J.; Xia, F.; Kang, Z.; Hu, W. “Bond cleavage, fragment modification and reassembly in enantioselective three-component reactions”. Nat Commun. 2015, 6, 5801. 4. Guo, X.; Hu, W. “Novel Multicomponent Reactions via Trapping of Protic Onium Ylides with Electrophiles”. Acc. Chem. Res. 2013, 46, 2427−2440. 5. Qiu, H.; Li, M.; Jiang, L.-Q.; Lv, F.-P.; Zan, L.; Zhai, C.-W.; Doyle, M. P.; Hu, W.-H. “Highly enantioselective trapping of zwitterionic intermediates by imines”. Nat. Chem. 2012, 4, 733−739.

16 Pd-initiated C1 Polymerization of Diazoacetates

Eiji Ihara Department of Materials Science & Biotechnology, Graduate School of Science & Engineering, Ehime University, 3 Bunkyo-cho, Matsuyama 790-8577, Japan [email protected]

C1 polymerization is a synthetic method for carbon-carbon (C-C) main chain polymers where the C-C main chain is constructed from one carbon unit, in contrast to conventional vinyl (C2) polymerization. Diazoacetate is one of the most common monomers for the C1 polymerization, affording polymers bearing an alkoxycarbonyl (ester) group on each main chain carbon atom, poly(alkoxycarbonylmethylene)s. We have demonstrated that some Pd-based initiating systems are effective for affording relatively high molecular weight polymers from a variety of diazoacetates. For example, -allylPdCl can initiate the polymerization from the Cl-Pd bond, yielding polymers having Cl at the -chain end. When NaBPh4 is added as an additive to - allylPdCl, Ph-Pd generated via transmetalation initiated the polymerization. With this system, the polymerization of diazoacetates with sterically bulky ester substituents proceeds in a controlled manner, affording polymers with narrow molecular weight distribution and well- defined block copolymers. Recently, we have established new Pd-based initiating systems utilizing naphthoquinone (nq) as a ligand, Pd(nq)/borate systems. When Pd(0)(nq)2 was reacted with NaBPh4, oxidative transmetalation is expected to afford a Pd(II) complex with Ph and nq-derived anions as ligands, the former of which initiated the polymerization of diazoacetates yielding high molecular weight polymers in high yield. On the other hand, the reaction of Pd2(dba)3 with 2,3-Cl2-nq was found to afford a new Pd(II) complex with Cl and naphthoquinonyl anions as ligands, which can afford syndiotactic polymers from diazoacetates.

The unique characteristic of polymers obtained from diazoacetates is that the ester substituents are densely packed along the polymer main chain. In comparison to their vinyl polymer counterpart, poly(alkyl acrylate), the effect of the accumulation of the substituents have been demonstrated in some examples using functional groups such as pyrene and phosphazene.

References 1. Ihara, E.; Shimomoto, H. “Polymerization of Diazoacetates: New Synthetic Strategy for C-C Main Chain Polymers” Polymer 2019, 174, 234-258. 2. Shimomoto, H.; Ichihara, S.; Hayashi, H.; Itoh, T.; Ihara, E. “Polymerization of Alkyl Diazoacetates Initiated by Pd(Naphthoquinone)/Borate Systems: Dual Role of Naphthoquinones as Oxidant and Anionic Ligand for Generating Active Pd(II) Species” Macromolecules 2019, 52, 6976-6987. 17

CURRICULUM VITAE – Eiji Ihara

Professor of Chemistry Department of Materials Science and Biotechnology, Graduate School of Science and Engineering, Ehime University, 3 Bunkyo-cho, Matsuyama 790- 8577, JAPAN Tel: +81 (89) 927-8547 Email: [email protected] Homepage: https://researchmap.jp/read0016596/?lang=english

Scientific Vita Since 2008 Ehime University, Professor, Department of Materials Science and Biotechnology 2000-2008 Ehime University, Associate Professor, Department of Materials Science and Biotechnology 1997-1998 University of Iowa, Postdoc, Department of Chemistry (R. F. Jordan group) 1992-2000 Hiroshima University, Assistant Professor, Department of Applied Chemistry 1987-1992 Kyoto University, Graduate Student, Department of Synthetic Chemistry

Research Field Polymer syntheses using diazocarbonyl compounds as monomers, development of functional polymers

Selected Awards and Recognition 1998 Award for Encouragement of Research in Polymer Science; The Society of Polymer Science, Japan

Representative Publications 1. Shimomoto, H.; Ichihara, S.; Hayashi, H.; Itoh, T.; Ihara, E.* “Polymerization of Alkyl Diazoacetates Initiated by Pd(Naphthoquinone)/Borate Systems: Dual Role of Naphthoquinones as Oxidant and Anionic Ligand for Generating Active Pd(II) Species” Macromolecules 2019, 52, 6976–6987. 2. Shimomoto, H.; Mori, T.; Itoh, T.; Ihara, E.* “Poly(β-keto enol ether) Prepared by Three- Component Polycondensation of Bis(diazoketone), Bis(1,3-diketone), and Tetrahydrofuran: Mild Acid-Degradable Polymers To Afford Well-Defined Low Molecular Weight Components” Macromolecules 2019, 52, 5761–5768. 3. Ihara, E.*; Shimomoto, H. “Polymerization of diazoacetates: New synthetic strategy for C-C main chain“ Polymer 2019, 174, 234-258. 4. Takaya, T,*; Oda, T.; Shibazaki, Y.; Hayashi, Y.; Shimomoto, H.; Ihara, E.*; Ishibashi, Y.; Asahi, T.*; Iwata, K.* “Excited-State Dynamics of Pyrene Incorporated into Poly(substituted methylene)s: Effects of Dense Packing of Pyrenes on Excimer Formation” Macromolecules 2018, 51, 5430–5439. 5. Shimomoto, H.; Kudo, T.; Tsunematsu, S.; Itoh, T.; Ihara, E.* “Fluorinated Poly(substituted methylene)s Prepared by Pd-Initiated Polymerization of Fluorine-Containing Alkyl and Phenyl Diazoacetates: Their Unique Solubility and Postpolymerization Modification” Macromolecules 2018, 51, 328–335. 6. Kato, F.; Chandra, A.; Tokita, M.; Asano, H.; Shimomoto, H.; Ihara, E.*; Hayakawa, T.* “Self- Assembly of Hierarchical Structures Using Cyclotriphosphazene-Containing Poly(substituted methylene) Block Copolymers” ACS Macro Lett. 2018, 7, 37-41. 7. Shimomoto, H.; Mukai, H.; Bekku, H.; Itoh, T.; Ihara, E.* “Ru-Catalyzed Polycondensation of Dialkyl 1,4-Phenylenebis(diazoacetate) with Dianiline: Synthesis of Well-Defined Aromatic Polyamines Bearing an Alkoxycarbonyl Group at the Adjacent Carbon of Each Nitrogen in the Main Chain Framework” Macromolecules 2017, 50, 9233–9238. 8. Shimomoto, H.; Kikuchi, M.; Aoyama, J.; Sakayoshi, D.; Itoh, T.; Ihara, E.* “Cyclopolymerization of Bis(diazocarbonyl) Compounds Leading to Well-Defined Polymers Essentially Consisting of Cyclic Constitutional Units” Macromolecules 2016, 49, 8459–8465.

18 Copper, silver, carbenes and nitrenes: A winning poker hand for hydrocarbon functionalization

Pedro J. Pérez Laboratorio de Catálisis Homogénea, Unidad Asociada al CSIC, CIQSO-Centro de Investigación en Química Sostenible and Departamento de Química, Universidad de Huelva, Campus de El Carmen 21007 Huelva, Spain. [email protected]

Group 11 metal complexes bearing trispyrazolylborate or N-heterocyclic carbene ligands have emerged as an useful tool toward the direct transfer of carbene or nitrene groups to an array of non-activated hydrocarbons, both saturated or unsaturated. In this contribution, an account of such behavior will be presented. On one hand, the use of diazoacetates and those catalysts has allowed the addition of the carbene unit to C=C bonds or the insertion into both Csp3-H or Csp2-H bonds,1 including challenging substrates such as methane2 or benzene3 (Scheme 1a). On the other hand, nitrene moieties have been transferred through those metal complexes acting as catalyst to a number of unsaturated organic molecules, in some cases providing novel transformations 4 toward molecular complexity. The direct metal-catalyzed nitrene insertion into Csp3-H or Csp2-H bonds5 has also been developed (Scheme 1b).

Scheme 1. Some reactions catalyzed by group 11 metal-based catalysts. References 1. Caballero, A.; Díaz-Requejo, M. M.; Fructos, M. R.; Olmos, A.; Urbano, J.; Pérez, P. J. Dalton Trans. 2015, 44, 20295-20307. 2. Caballero, A.; Despagnet-Ayoub, E.; Díaz-Requejo, M. M.; Díaz-Rodríguez, A.; González- Núñez, M. E.; Mello, R.; Muñoz, B. K.; Solo Ojo, W.; Asensio, G.; Etienne, M.; Pérez, P. J. Science 2011, 332, 835-838 3. Fructos M. R.; Belderrain, T. R.; Frémont, P.; Scott, N. M.; Nolan, S. P.; Díaz-Requejo, M. M.; Pérez, P. J. Angew. Chem. Int. Ed. 2005, 44, 5284-5288. 4. Llaveria, J.; Beltrán, A.; Sameera, W. M.C.; Locati, A.; Díaz-Requejo, M. M.; Matheu, M.I.; Castillón, S.; Maseras, F.; Pérez, P. J. J. Am. Chem. Soc. 2014, 136, 5342–5350. (b) Rodríguez, M. R.; Beltrán, A.; Mudarra, A. L.; Álvarez, E.; Maseras, F.; Díaz-Requejo, M. M.; Pérez, P. J. Angew. Chem. Int. Ed. 2017, 56, 12842–12847. 5. Fructos, M. R.; Trofimenko, S.; Díaz-Requejo, M. M.; Pérez, P. J. J. Am. Chem. Soc. 2006, 128, 11784-11791.

19 CURRICULUM VITAE – Pedro J. Pérez Professor of Inorganic Chemistry, Department of Chemistry, Center for Research in Sustainable Chemistry (CIQSO), University of Huelva, Spain. e-mail: [email protected] URL for web site (English): http://www.uhu.es/ciqso/catalisis-homogenea.html https://publons.com/researcher/2787416/pedro-j-perez/

EDUCATION 1991 PhD in Chemistry (excellent Cum Laude), University of Sevilla, Spain. (Advisor: Prof. E. Carmona).

PREVIOUS POSITIONS 1995-2005 Senior Lecturer. Department of Chemistry, University of Huelva, Spain. 1993 – 1995 Junior Lecturer, Department of Chemistry, University of Huelva, Spain. 1994 (3 months) Visiting Research Scientist, Dupont Experimental Station, Wilmington, Delaware (USA). 1991-1993 Postdoctoral Researcher, (Prof. Maurice Brookhart supervisor), Fulbright Scholar Fellowship, Dept. Chemistry, University of North Carolina, Chapel Hill (USA). 1987-1991 Predoctoral researcher, Graduate School, Dept. of Inorganic Chemistry, University of Seville, Spain. RESEARCH INTEREST Late transition metal organometallic and catalysis, carbene, nitrene and oxo transfer, C-G functionalization, hydrocarbon catalytic modification

FELLOWSHIPS AND AWARDS 2018 Member of the Academia Europaea 2018 AIQBE Research Award University of Huelva 2017 Distinguished Career Research Award Faculty of Experimental Sciences, University of Huelva 2016 Gold Medal and Research Award of the Royal Spanish Chemical Society 2015 Homogeneous Catalysis Award of the Royal Society of Chemistry (UK). 2014 Member of the National Academy of Sciences of Spain 2014 Fellow of the Royal Society of Chemistry (UK). 2007 Inorganic Chemistry Award, Royal Society of Chemistry of Spain.

REPRESENTATIVE PUBLICATIONS 1) Caballero, A.; Despagnet-Ayoub, E.; Díaz-Requejo, M. M.; Díaz-Rodríguez, A.; González-Núñez, M. E.; Mello, R.; Muñoz, B. K.; Ojo, W.-S.; Asensio, G.; Etienne, M.; Pérez, P. J. Silver-catalyzed C-C bond formation between methane and ethyl diazoacetate in supercritical CO2. Science, 2011, 332, 835-838 2) Maestre, L.; Sameera, W. M. C.; Díaz-Requejo, M. M.; Maseras, F.; Pérez, P. J. “A General Mechanism for the Copper- and Silver-Catalyzed Olefin Aziridination Reactions: Concomitant Involvement of the Singlet and Triplet Pathways”. J. Am. Chem. Soc. 2013, 135, 1338-1348. 3) Llaveria, J.; Beltrán, A.; Sameera, W. M. C.; Locati, Abel; Díaz-Requejo, M. M.; Matheu, M. I.; Castillon, S.; Maseras, F.; Pérez, P. J. “Chemo-, Regio-, and Stereoselective Silver-Catalyzed Aziridination of Dienes: Scope, Mechanistic Studies, and Ring-Opening Reactions”. J. Am. Chem. Soc. 2014, 136, 5342-5350. 4) Conde, A.; Sabenya, G.; Rodríguez, M.; Postils, V.; Luis, J. M.; Díaz-Requejo, M. M.; Costas, M.; Pérez, P. J. “Iron and Manganese Catalysts for the Selective Functionalization of Arene C(sp(2))-H Bonds by Carbene Insertion”. Angew. Chem. Int. Ed. 2016, 55, 6530-6534. 5) Rodríguez, M. R.; Beltrán, A.; Mudarra, A. L.; Álvarez, E.; Maseras, F.; Diaz-Requejo, M. M.; Pérez, P. J. “Catalytic Nitrene Transfer To Alkynes: A Novel and Versatile Route for the Synthesis of Sulfinamides and Isothiazoles”. Angew. Chem. Int. Ed. 2017, 56, 12848-12847. 6) Maestre, L.; Dorel, R.; Pablo, O.; Escofet, I.; Sameera, W. M. C.; Álvarez, E.; Maseras, F.; Díaz-Requejo, M. M.; Echavarren, A. M.; Pérez, P. J. “Functional-Group-Tolerant, Silver-Catalyzed N-N Bond Formation by Nitrene Transfer to ”. J. Am. Chem. Soc. 2017, 139, 2216-2223. 7) Carreras, J.; Caballero, A.; Pérez, P. J. “Enantio- and Diastereoselective Cyclopropanation of 1- Alkenylboronates: Synthesis of 1-Boryl-2,3-Disubstituted Cyclopropanes”. Angew. Chem. Int. Ed. 2018, 57, 2334-2338. 8) Olmos, A.; Gava, R.; Noverges, B.; Bellezza, D.; Jacob, K.; Besora, M.; Sameera, W. M. C.; Etienne, M.; Maseras, F.; Asensio, G.; Caballero, A.; Pérez, P. J. “Measuring the Relative Reactivity of the Carbon- Hydrogen Bonds of Alkanes as ”. Angew. Chem. Int. Ed. 2018, 57, 13848-13852.

20 Stereoselective Carbene Insertion into Strained C–Si Bonds and Carbene- based Polymer Synthesis

Jianbo Wang College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China [email protected]

Carbene-based transformations under transition metal catalysis have been extensively explored in the past decades. The typical carbene transfer reactions involve insertions, cyclopropanations and ylide generations. In the past decade, a new type of transition-metal- catalyzed carbene reaction has emerged, in which the carbene precursor diazo compounds have been explored as the cross-coupling partners in C-C single bond or C=C double bond formations.1 As a continuation of our exploration in this arena,2 we present here our recent study on a highly regio- and enantioselective carbene insertion into strained C-Si bonds.

On the other hand, the application of highly efficient transition-metal-catalyzed reactions to the synthesis of polymers has attracted great attentions. In particular, transition-metal-catalyzed cross-coupling and olefin metathesis have been extensively applied in polymerization chemistry. On the contrary, carbene-based transformations, such as insertions, cyclopropanations and cross- couplings, have been rarely utilized in polymer synthesis. We have recently launched a program to systematically explore the application of carbene-based transformation in polymerization chemistry. In this lecture, we would like to present some of our initial results along this line.3

References 1. Xia, Y.; Qiu, D.; Wang, J. “Transition-Metal-Catalyzed Cross-Couplings through Carbene Migratory Insertion” Chem. Rev. 2017, 117, 13810-13889. 2. Liu, Z.; Tan, H.; Fu, T.; Xia, Y.; Qiu, D.; Zhang, Y.; Wang, J. “Pd(0)-Catalyzed Carbene Insertion into Si-Si and Sn-Sn Bonds” J. Am. Chem. Soc. 2015, 137, 12800-12803. 3. Zhou, Q.; Gao, Y.; Xiao, Y.; Yu, L.; Fu, Z.; Li, Z.; Wang, J. “Palladium-Catalyzed Carbene Coupling of N-Tosylhydrazones and Arylbromides to Synthesize Cross-Conjugated Polymers” Polym. Chem. 2019, 10, 569-573.

21

CURRICULUM VITAE –Jianbo Wang

Professor of Chemistry College of Chemistry and Molecular Engineering Peking University, Beijing 100871, China Tel: 86 (10) 6275-7248 Email: [email protected] Homepage: http://old.chem.pku.edu.cn/physicalorganic/home.htm

Scientific Vita Since 1999 Professor at Peking University 1995-1999 Associate professor at Peking University 1993-1995 Postdoctoral Fellow, University of Wisconsin-Madison (with Prof. Howard E. Zimmerman) 1990-1993 Postdoctoral Fellow, University of Geneva (with Prof. Charles W. Jefford) 1984-1990 Ph.D., Hokkaido University (with Prof. Hiroshi Suginome) 1979-1983 B.S., Nanjing University of Science and Technology

Research Field Catalytic reaction with carbene as reactive intermediates; radical reactions; organoboron and organofluorine chemistry; polymerization chemistry.

Selected Awards and Recognition 1997 Excellent Young Faculty Award by the Ministry of Education 2000 Trans-Century Training Programme Foundation for the Talents by the Ministry of Education 2002 National Outstanding Young Investigator Found by Natural Science Foundation 2005 Cheung Kong Scholarship 2006 Eli Lilly Research Excellence Award (ELSEA) 2007 Baogang Education Excellence Award 2008 Chinese Chemical Society-BASF Award 2011 Second Prize of Science and Technology of Beijing Municipal Government 2015 First Prize of Ministry of Education in Natural Science Research 2016 Baeyer Investigator Award 2018 Chun-Tsung Endowment Outstanding Contribution Award-Excellent Tutor

Representative Publications 1. Zhang, R.; Zhang, Z.; Zhou, Q.; Yu, L.; Wang, J. “Generation of Difluoroketenimine and Its Application in the Synthesis of -Difluoro--amino Amides” Angew. Chem. Int. Ed. 2019, 58, 5744-5748. 2. Zhang, Z.; Sheng, Z.; Yu, W.; Wu, G.; Zhang, R.; Chu, W.-D.; Zhang, Y.; Wang, J. “Catalytic Asymmetric Trifluoromethylthiolation via Enantioselective [2,3]-Sigmatropic Rearrangement of Sulfonium Ylides.” Nature Chem. 2017, 9, 970-976. 3. Chu, W.-D.; Zhang, L.; Zhang, Z.; Zhou, Q.; Mo, F.; Zhang, Y.; Wang, J. “Enantioselective Synthesis of Trisubstituted via Cu(I)-Catalyzed Coupling of Diazoalkanes with Terminal Alkynes.” J. Am. Chem. Soc. 2016, 138, 14558-14561. 4. Ye, F.; Qu, S.; Zhou, L.; Peng, C.; Wang, C.; Cheng, J.; Hossain, M. L.; Liu, Y.; Zhang, Y.; Wang, Z.-X.; Wang, J. “Pd-Catalyzed C-H Functionalization of Acyldiazomethane and Tandem Cross- Coupling Reactions” J. Am. Chem. Soc. 2015, 137, 4435-4444. 5. Xia, Y.; Liu, Z.; Liu, Z.; Ge, R.; Ye, F.; Hossain, M.; Zhang, Y.; Wang, J. “Formal Carbene Insertion into C-C Bond: Rh(I)-Catalyzed Reaction of Benzocyclobutenols with Diazoesters” J. Am. Chem. Soc. 2014, 136, 3013-3015.

22 Oxidative Gold(I) Catalysis Employing Heteroatom-Terminated Substrates

Liming Zhang Department of Chemistry and Biochemistry, University of California, Santa Barbara, CA 93106, USA [email protected]

α-Oxo gold carbenes can be generated as reactive intermediates upon gold(I)-promoted oxidation of alkynes by pyridine/quinoline N-oxides (Scheme A).1 In some cases, the adducts of these nucleophilic oxidants to alkynes could directly undergo carbene-type reactions while bypassing the intermediacy of these carbene species. A range of synthetic methods have been developed based on this oxidative strategy.2 The alkyne substrates are mostly limited to those with the C-C triple bond substituted by C-, N- or O-based groups. To broaden the substrate scope and explore new synthetic opportunities, we have recently employed silyl- and MIDA-terminated alkynes as substrates (Scheme B). Under the regime of the oxidative gold catalysis, these functionalized alkynes would offer access to new types of α-oxo gold carbenes, where the carbene center is substituted by a heteroatom such as Si and B. In the case of TBS alkynes, we observed the elusive Wolff rearrangements, which had not been documented in gold carbene chemistry.3 With the MIDA boronate terminating the C-C triple bond, these boron-functionalized alkynes undergo insertions into a surprisingly broad range of C-H bonds, cyclopropanations of alkenes and the Friedel-Crafts reactions with high efficiencies, and deliver valuable alpha-BMIDA ketone products.

Oxidative Gold(I) Catalysis: A General Depiction

Oxidative Gold(I) Catalysis: Using Si/B‐Terminated Alkynes

References 1 Ye, L.; Cui, L.; Zhang, G.; Zhang, L. 'Alkynes as Equivalents of -Diazo Ketones in Generating -Oxo Metal Carbenes: A Gold-Catalyzed Expedient Synthesis of Dihydrofuran- 3-Ones' J. Am. Chem. Soc. 2010, 132, 3258-3259. 2 Zhang, L. 'A Non-Diazo Approach to Α-Oxo Gold Carbenes Via Gold-Catalyzed Alkyne Oxidation' Acc. Chem. Res. 2014, 47, 877–888. 3 Zheng, Y.; Zhang, J.; Cheng, X.; Xu, X.; Zhang, L. 'Wolff Rearrangement of Oxidatively Generated Α-Oxo Gold Carbenes: An Effective Approach to Silylketenes' Angew. Chem., Int. Ed. 2019, 58, 5241-5245.

23

CURRICULUM VITAE – Liming Zhang

Professor of Chemistry & Biochemistry Department of Chemistry & Biochemistry, The University of California, Santa Barbara, California 93106, USA Tel: 001 (805) 893-7392 Email: [email protected] Homepage: https://labs.chem.ucsb.edu/zhang/liming/index.html/

Scientific Vita Since 2013 Professor, Department of Chemistry and Biochemistry, UC Santa Barbara 2011-2013 Associate Professor, Department of Chemistry and Biochemistry, UC Santa Barbara 2009-2011 Assistant Professor, Department of Chemistry and Biochemistry, UC Santa Barbara 2005-2009 Assistant Professor, Department of Chemistry, University of Nevada, Reno 2003-2005 Postdoctoral Fellow with Professor Sergey A. Kozmin, University of Chicago

Research Field Asymmetric catalysis, gold catalysis, synthetic methodology, carbohydrate synthesis, ligand design and development

Selected Awards and Recognition 2014 One of Highly Cited Researcher by Thomson Reuters (http://highlycited.com/index.htm) 2009 2009 Alfred P. Sloan Research Fellow 2009 Spring 2009 CAPA (Chinese American Chemistry & Chemical Biology Professor Association) Distinguished Junior Faculty Award. 2008 Mousel-Feltner Award for Excellence in Research and/or Creative Activity (UNR) 2008 NSF CAREER Award 2008 Amgen Young Investigator’s Award 2007 Thieme Journal Award 2007 Unrestricted gift by Merck & Co, Inc. 2007 Ralph E. Powe Junior Faculty Enhancement Award

Representative Publications 1. Zheng, Y.; Zhang, J.; Cheng, X.; Xu, X.; Zhang, L. 'Wolff Rearrangement of Oxidatively Generated Α-Oxo Gold Carbenes: An Effective Approach to Silylketenes' Angew. Chem., Int. Ed. 2019, 58, 5241-5245. 2. Cheng, X.; Wang, Z.; Quintanilla, C. D.; Zhang, L. 'Chiral Bifunctional Phosphine Ligand Enabling Gold-Catalyzed Asymmetric Isomerization of Alkyne to Allene and Asymmetric Synthesis of 2,5- Dihydrofuran' J. Am. Chem. Soc. 2019, 141, 3787–3791.. 3. Bai, Y.-B.; Luo, Z.; Wang, Y.; Gao, J.-M.; Zhang, L. 'Au-Catalyzed Intermolecular [2+2] Cycloadditions between Chloroalkynes and Unactivated Alkenes' J. Am. Chem. Soc. 2018, 140, 5860-5865. 4. Li, T.; Zhang, L. 'Bifunctional Biphenyl-2-ylphosphine Ligand Enables Tandem Gold-Catalyzed Propargylation of and Unexpected Cycloisomerization' J. Am. Chem. Soc. 2018, 140, 17439–17443. 5 Wang, Y.; Zarca, M.; Gong, L.-Z.; Zhang, L. 'A C–H Insertion Approach to Functionalized Cyclopentenones' J. Am. Chem. Soc. 2016, 138, 7516–7519.

24 Metalloradical Catalysis: Stepwise Radical Pathways for Catalytic Carbene and Nitrene Transfers

X. Peter Zhang Department of Chemistry, Boston College, Chestnut Hill, MA 02467, USA [email protected]

Organic synthesis has been dominated by chemical reactions that are based on two-electron ionic processes, either stoichiometrically or in catalytic fashion. While one-electron radical chemistry is equally rich and has been demonstrated with a number of unique features, its application in organic synthesis has been hampered by several enduring challenges. Over the past two decades, my laboratory has been in the process of formulating “Metalloradical Catalysis” (MRC) as a general concept to guide the development of fundamentally new approaches for controlling both reactivity and stereoselectivity of radical reactions. In essence, metalloradical catalysis aims for the development of metalloradical-based systems for catalytic generation of carbon-, nitrogen-, and oxygen-centered radicals from common organic compounds without the need of radical initiators or the use of light. The subsequent reactions of the resulting organic radical intermediates, which remain covalently bonded to the metal center, can be selectively controlled by the catalyst. For achieving enantioselective radical reactions via MRC, we have developed a family of unique chiral metalloradical catalysts based on structurally well-defined Co(II) complexes of D2-symmetric chiral porphyrins with tunable electronic, steric, and chiral environments. These Co(II)-based metalloradical catalysts have been shown to be highly effective for a wide range of stereoselective organic reactions, including olefin cyclopropanation, olefin aziridination, C–H alkylation and C–H amination. Due to their distinctive radical mechanisms that involve unprecedented -metalloalkyl and -metalloaminyl radical intermediates, the Co(II)-based metalloradical systems enable addressing some long-standing problems in these important organic transformations.

We have shown that Co(II) complexes of D2-symmetric chiral amidoporphyrins [Co(D2-Por*)], as stable metalloradicals with well-defined d7 electronic configuration, have the unusual capability of activating diazo compounds and organic to generate -Co(III)-alkyl radicals (also known as Co(III)-carbene radicals or Co(III)-radical carbenes) and -Co(III)-aminyl radicals (also known as Co(III)-nitrene radicals or Co(III)-radical nitrenes), respectively. The - metalloalkyl and -metalloaminyl radicals can undergo common radical reactions, including radical addition, H-atom abstraction and radical substitution, leading to development of new catalytic systems for stereoselective carbene and nitrene transfer reactions via stepwise radical pathways.

25

CURRICULUM VITAE – X. Peter Zhang

Professor of Chemistry

Department of Chemistry; Merkert Chemistry Cente; Boston College; 2609 Beacon Street; Chestnut Hill, MA 02467, USA Tel: 001 (617) 552-1483 Email: [email protected] Homepage: https://www2.bc.edu/peter-zhang/

Scientific Vita Since 2015 Boston College, Professor, Department of Chemistry. 2010-2015 University of South Florida, Professor, Department of Chemistry. 2006-2010 University of South Florida, Associate Professor, Department of Chemistry 2001-2006 University of Tennessee, Assistant Professor, Department of Chemistry 1996-2001 Massachusetts Institute of Technology, Postdoctoral Fellow, Department of Chemistry

Research Field Development and Application of Metalloradical Catalysis (MRC) for Stereoselective Radical Reactions.

Selected Awards and Recognition 1997 NIH National Research Service Award 2003 ORAU Ralph Powe Junior Faculty Award 2005 Chancellor’s Professional Development Award, University of Tennessee 2006 NSF CAREER Award 2007 Outstanding Research Achievement Award, University of South Florida 2008 University Research Merit Award, University of South Florida 2009 Thieme Chemistry Journal Award

Representative Publications 1. Hu, Y.; Lang, K.; Li, C.-Q.; Gill; J. B.; Kim, I.; Lu, H.-J.; Fields, K. B.; Marshall, M. K.; Cheng, Q.- G.; Cui, X.; Wojtas, L.; Zhang, X. P. “Enantioselective Radical Construction of 5-Membered Cyclic Sulfonamides by Metalloradical C−H Amination” J. Am. Chem. Soc. 2019, 141, jacs.9b08894. 2. Lang, K.; Torker, S.; Wojtas, L.; Zhang, X. P. “Asymmetric Induction and Enantiodivergence in Catalytic Radical C–H Amination via Enantiodifferentiative H-Atom Abstraction and Stereoretentive Radical Substitution” J. Am. Chem. Soc. 2019, 141, 12388–12396. 3. Hu, Y.; Lang, K.; Tao, J.-R.; Marshall, M. K.; Cheng, Q.-G.; Cui, X.; Wojtas, L.; Zhang, X. P. “Next-Generation D2-Symmetric Chiral Porphyrins for Cobalt(II)-Based Metalloradical Catalysis: Catalyst Engineering by Distal Bridging” Angew. Chem. Int. Ed. 2019, 58, 2670–2674. 4. Li, C.-Q.; Lang, K.; Lu, H.-J.; Hu, Y.; Cui, X.; Wojtas, L.; Zhang, X. P. “Catalytic Radical Process for Enantioselective Amination of C(sp3)–H Bonds” Angew. Chem. Int. Ed. 2018, 57, 16837–16841. 5. Wang, Y.; Wen, X.; Cui, X.; Zhang, X. P. “Enantioselective Radical Cyclization for Construction of 5-Membered Ring Structures by Metalloradical C–H Alkylation” J. Am. Chem. Soc. 2018, 140, 4792–4796. 6. Wen, X.; Wang, Y.; Zhang, X. P. “Enantioselective Radical Process for Synthesis of Chiral Indolines by Metalloradical Alkylation of Diverse C(sp3)–H Bonds” Chem. Sci. 2018, 9, 5082– 5086. 7. Jiang, H.-L.; Lang, K.; Lu, H.-J.; Wojtas, L.; Zhang, X. P. “Asymmetric Radical Bicyclization of Allyl Azidoformates via Cobalt(II)-Based Metalloradical Catalysis” J. Am. Chem. Soc. 2017, 139, 9164–9167. 8. Wang, Y.; Wen, X.; Cui, X.; Wojtas, L.; Zhang, X. P. "Asymmetric Radical Cyclopropanation of Alkenes with In Situ-Generated Donor-Substituted Diazo Reagents via Co(II)-Based Metalloradical Catalysis" J. Am. Chem. Soc. 2017, 139, 1049–1052.

26 Asymmetric Catalytic Carbene Insertion into N–H Bonds

Qi-Lin Zhou Institute of Elemento-organic Chemistry, Nankai University, Tianjin 300071, China [email protected]

Chiral amines are ubiquitous in natural products, pharmaceuticals and agrochemicals. The development of highly enantioselective C–N bond-forming reactions is thus of long-standing interest in synthetic chemistry. Transition-metal-catalyzed carbenoid insertion into N–H bonds of amines has proven a straightforward method in this respect, benefitting from mild reaction conditions, good functional group tolerance, and readily available reactants. However, the enantioselective catalytic carbenoid insertion into N–H bonds of amines remains a challenge. In last decade we developed several catalyst systems, which are effective for the carbenoid insertions into N–H bonds of amides, aromatic and aliphatic amines, providing highly enantioselective accesses to chiral non-natural derivatives.

References 1. Zhu, S.-F.; Zhou, Q.-L. “Transition-metal-catalyzed enantioselective heteroatom–hydrogen bond insertion reactions”, Acc. Chem. Res. 2012, 45, 1365-1377. 2. Xu, B.; Zhu, S.-F.; Zuo, X.-D.; Zhang, Z.-C.; Zhou, Q.-L. “Enantioselective N‒H of α-aryl-α-diazoketones: An efficient route to chiral α-aminoketones”, Angew. Chem. Int. Ed. 2014, 53, 3913-3916. 3. Xu, B.; Li, M.-L.; Zuo, X.-D.; Zhu, S.-F.; Zhou, Q.-L. “Catalytic asymmetric arylation of α- aryl-α-diazoacetates with derivatives”, J. Am. Chem. Soc. 2015, 137, 8700-8703. 4. Song, X.-G.; Ren, Y.-Y.; Zhu, S.-F.; Zhou, Q.-L. “Enantioselective copper-catalyzed intramolecular N‒H bond insertion: Synthesis of chiral 2-carboxy tetrahydroquinolines”, Adv. Syn. Catal. 2016, 358, 2366-2370. 5. Guo, J.-X.; Zhou, T.; Xu, B.; Zhu, S.-F.; Zhou, Q.-L. “Enantioselective synthesis of - alkenyl--amino acids via N‒H insertion reaction”, Chem. Sci. 2016, 7, 1104-1108. 6. Ren, Y.-Y.; Zhu, S.-F.; Zhou, Q.-L. “Chiral proton-transfer shuttle catalysts for carbene insertion reactions”, Org. Biomol. Chem. 2018, 16, 3087-3094. 7. Li, M.-L.; Yu, J.-H.; Li, Y.-H.; Zhu, S.-F.; Zhou, Q.-L. “Highly enantioselective carbene insertion into N–H bonds of aliphatic amines”, Science 2019, 366, 990–994.

27 CURRICULUM VITAE – Qi-Lin Zhou

Professor of Chemistry Cheung Kong Scholar Institute of Elemento-organic Chemistry College of Chemistry Nankai University 94 Weijin Rd., Tianjin 300071, CHINA Tel: 85-22-2350 0011 Email: [email protected]

Homepage: http://zhou.nankai.edu.cn/

Scientific Vita Since 1999 Professor, Cheung Kong Scholar, Institute of Elemento-organic Chemistry, Nankai University, Tianjin 1996-1999 Associate Professor, Institute of Fine Chemicals, East China University of Science and Technology, Shanghai 1994-1996 Postdoctoral associate, Department of Chemistry, Trinity University, San Antonio (with Prof. Michael Doyle) 1992-1994 Postdoctoral associate, Department of Chemistry, Basel University, Basel (with Prof. Andreas Pfaltz) 1990-1992 Postdoctoral associate, Max-Planck Institute of Polymer Science, Mainz (with Prof. Klaus Müllen) 1988-1991 Postdoctoral associate, Institute of Fine Chemicals, East China University of Science and Technology, Shanghai (with Prof. Zheng-Hua Zhu) 1982-1987 Ph.D., Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai (with Prof. Yao-Zeng Huang) 1978-1982 B.Sc., Department of Chemistry, Lanzhou University, Lanzhou

Research Field Synthetic methodology, Organometallics, Asymmetric catalysis, Synthesis of biologically active compounds

Selected Awards and Recognitions 1997 Award for Outstanding Young Scientists (National Natural Science Foundation of China) 1999 Cheung Kong Scholar (Ministry of Education of China) 2005 Prize for Creation in Organic Synthesis (Chinese Chemical Society) 2006 Yao-Zeng Huang Prize of Organometallics (Chinese Chemical Society) 2007 JSPS Fellowship Award (Japan Society for the Promotion of Science) 2007 Prize of Natural Science of Tianjin (1st class) 2009 Member of Chinese Academy of Sciences 2012 Prize of Chiral Chemistry (Chinese Chemical Society) 2013 Fellow of Royal Society of Chemistry 2014 Novartis Lecturer at the Scripps Research Institute 2014 National Outstanding Scientist (China Association for Science and Technology) 2017 Boehringer-Ingelheim Lecturer at California Institute of Technology 2018 Chemistry Contribution Prize (Chinese Chemical Society-Sinopec) 2018 Future Science Prize---The Physical Science Prize

28 Asymmetric Catalytic Constructions of Heterocycles and Carbocycles by Cycloaddition

Zachary T. Ball Department of Chemistry, Rice University, Houston, Texas 77005, USA [email protected]

Dirhodium metallopeptides are accessible by direct ligation of a heteroleptic dirhodium complex to carboxylate side chains of fully deprotected peptides. Metallopeptides catalyze selective C-C bond formation of diazo reagents with a variety of small molecule and polypeptide substrates. The peptide ligand creates an ideal modular framework for the control of reaction selectivity. Examples presented demonstrate peptide ligand design as a facile approach to controlling stereoselective reactions. The discovery and exploitation of exogenous axial ligands to control the reactivity of rhodium metallocarbene intermediates will be discussed.

References (1) Sambasivan, R.; Zheng, W.; Burya, S. J.; Popp, B. V.; Turro, C.; Clementi, C.; Ball, Z. T. A tripodal peptide ligand for asymmetric Rh(II) catalysis highlights unique features of on-bead catalyst development. Chem. Sci. 2014, 5, 1401–1407. DOI: 10.1039/C3SC53354A. (2) Sambasivan, R.; Ball, Z. T. Metallopeptides for asymmetric dirhodium catalysis. J. Am. Chem. Soc. 2010, 132, 9289–9291. DOI: 10.1021/ja103747h. (3) Kundu, R.; Ball, Z. T. Rhodium-catalyzed cysteine modification with diazo reagents. Chem. Commun. 2013, 49, 4166–4168. DOI: 10.1039/c2cc37323h.

29 CURRICULUM VITAE – Zachary T. Ball

Professor of Chemistry Department of Chemistry, MS 60, Rice University 6100 Main St., Houston, TX 77005 Tel: 713.348.6159 Email: [email protected] Homepage: http://ztb.rice.edu/

Scientific Vita 2006– Professor of Chemistry, Rice University (Assoc. Prof. 2013–2019, Houston, TX Asst. Prof. 2006–2013) 2017– Director, Institute of Biosciences & Bioengineering, Rice Houston, TX University (IBB) 2015– Smalley–Curl Institute (frmly Smalley Institute for Nanoscale Houston, TX Science and Technology), Rice University 2014–2019 Associate Chair for Undergraduate Studies Houston, TX 2006–2008 Norman Hackerman–Welch Young Investigator, Rice University Houston, TX 2004–2006 Miller Research Fellow, Miller Institute for Basic Research in Berkeley, CA Science, UC–Berkeley. Adviser: Prof. Jean M. J. Fréchet 1999–2004 Graduate Research and Teaching Assistant, Stanford University Stanford, CA 1997–1999 Undergraduate Research, Harvard University Cambridge, MA Summer 1998 Research Intern, Schering-Plough Research Institute Kenilworth, NJ

Research Field Transition-metal catalysis, peptide and protein chemistry, bioconjugation, bioorganic and bioinorganic chemistry, metallotherapeutics

Selected Awards and Recognition 2017 Thieme Chemistry Journal Awardee 2011–2016 NSF CAREER award 2006–2009 Norman Hackerman–Welch Young Investigator Award 2004–2006 Miller Research Fellow, Miller Institute for Basic Research in Science, University of California, Berkeley. 2001–2004 Althouse Family Fellow, Stanford Graduate Fellowship 1996–1999 Undergraduate Research Fellowship, Harvard College Research Program 1996–1999 John Harvard Honorary Scholarship, Harvard University 1995 National Merit Scholar

Representative Publications (61) Mangubat-Medina, A. E.; Martin, S. C.; Hanaya, K.; Ball, Z. T. A Vinylogous Photocleavage Strategy Allows Direct Photocaging of Backbone Amide Structure. J. Am. Chem. Soc. 2018, 140, 8401–8404. DOI: 10.1021/jacs.8b04893. (58) Ohata, J.; Ball, Z. T. A Hexa-rhodium Metallopeptide Catalyst for Site-Specific Functionalization of Natural Antibodies. J. Am. Chem. Soc. 2017, 139, 12617–12622. DOI: 10.1021/jacs.7b06428. (55) Martin, S. C.; Vohidov, F.; Wang, H.; Knudsen, S. E.; Marzec, A. A.; Ball, Z. T. Designing Selectivity in Dirhodium Metallopeptide Catalysts for Protein Modification. Bioconjugate Chem. 2017, 28, 659–665. DOI: 10.1021/acs.bioconjchem.6b00716. (41) A tripodal peptide ligand for asymmetric Rh(II) catalysis highlights unique features of on-bead catalyst development. Sambasivan, R.; Zheng, W.; Burya, S. J.; Popp, B. V.; Turro, C.; Clementi, C.; Ball, Z. T. Chem. Sci. 2014, 5, 1401–1407. doi:10.1039/C3SC53354A.

30 %   !  #!$   "  ! &  Ā % )>@BIĀ2?;F7BC;DIȀĀ'D=3?D3ȀĀ*'Ā$"$##ȀĀ2!0!'!Ā )>3;=%ĀC4=3<7I&7>@BI!76EĀ Ā 1:7Ā67F7=@A>7?DĀ@8Ā?7GĀB735D;@?CĀ3?6Ā53D3=ICDCĀ8@BĀD:7Ā@H;63D;F7Ā5B@CC 5@EA=;?9Ā@8Ā( +Ā4@?6CĀG;D:Ā ( +ȀĀ. +Ā3?6Ā/ +Ā4@?6CĀG;==Ā47Ā6;C5ECC76!Ā0DB3D79;53==IȀĀD:7C7ĀB735D;@?CĀ3==@GĀ8@BĀD:7ĀCI?D:7C;CĀ@8Ā 5@>A=7HĀ>@=75E=7CĀ8B@>ĀD:7;BĀ5@?CD;DE7?DĀ5@>A@?7?DCȀĀ>;?;>;J;?9ĀD:7Ā?776Ā8@BĀ8E?5D;@?3=Ā9B@EAĀ 35D;F3D;@?Ā3?6Ā>3?;AE=3D;@?!Ā0A75;8;53==IȀĀB:@6;E>Ā3?6Ā;B;6;E>Ā53D3=ICDCĀ8@BĀ@H;63D;F7Ā3==I=;5Ā( +Ā 8E?5D;@?3=;J3D;@?Ā@8ĀD7B>;?3=ȀĀ6; Ā3?6ĀDB;CE4CD;DED76Ā@=78;?CĀG;==Ā47ĀAB7C7?D76!Ā-75:3?;CD;5Ā;?C;9:DCĀ =736;?9ĀD@Ā?7GĀB735D;@?ĀAB@D@5@=CĀ8@BĀB79;@5:7>;53=Ā5@?DB@=ȀĀ3?6Ā?7GĀ53D3=ICDĀ67C;9?CĀD:3DĀ835;=;D3D7Ā 7?3?D;@C7=75D;F7ĀB735D;@?CĀG;D:Ā?;DB7?7Ā3>;63D;?9ĀB7397?DCĀG;==Ā47Ā67C5B;476!Ā,==ECDB3D;F7Ā7H3>A=7CĀ@8Ā 7>7B97?DĀ3AA=;53D;@?CĀG;==Ā47ĀAB@F;676!Ā Ā 

31

Simon B. Blakey

Department of Chemistry Phone: (404) 727-6738 Emory University [email protected] Atlanta GA 30322

Education 1998-2002 Ph.D., Chemistry, University of Cambridge, United Kingdom 1994-1997 B.Sc. (Hons.), Chemistry & Biochemistry, University of Auckland, New Zealand

Work History/Research Experience 2019- Professor of Chemistry Emory University, Atlanta, GA 2011-2019 Associate Professor of Chemistry Emory University, Atlanta, GA 2005-2011 Assistant Professor of Chemistry Emory University, Atlanta, GA 2002-2005 Postdoctoral Research Fellow with Professor David MacMillan California Institute of Technology, Pasadena, CA Cross coupling reactions with quaternary ammonium salts as pseudohalides. Application of organocatalytic indole alkylation to the total synthesis of diazonamide A. 1998-2002 Graduate Research with Professor Ian Paterson University of Cambridge, Cambridge, U.K. Synthesis of an advanced macrolide intermediate for the aplyronines. Selected Publications “Rh(III) and Ir(III)Cp* Complexes Provide Complementary Regioselectivity Profiles in Intermolecular Allylic C-H Amidation Reactions” Jacob S. Burman, Robert Harris, Caitlin M. B. Farr, John Bacsa, Simon B. Blakey* ACS Catal. 2019, 9, 5474-79 DOI: 10.1021/acscatal.9b01338

“Intermolecular Allylic Etherification of Internal Olefins” Taylor A. F. Nelson, and Simon B. Blakey* Angew. Chem. Int. Ed. 2018, 57, 14911; DOI:10.1002/anie.201809863

“Regioselective Intermolecular Allylic C–H Amination of Disubstituted Olefins via Rh-π-allyl Intermediates” Jacob S. Burman and Simon B. Blakey. Angew. Chem. Int. Ed. 2017, 56, 13666 DOI:10.1002/anie.201707021

“KOtBu-Initiated Aryl C-H Iodination: A Powerful Tool for the Synthesis of High Electron Affinity Compounds” Qinqin Shi, Siyuan Zhang, Junxiang Zhang, Victoria F. Oswald, Aram Amassian, Seth R. Marder, Simon B. Blakey, J. Am. Chem. Soc. 2016, 138, 3946. DOI:10.1021/jacs.5b12259 “Iridium(III)-bis(imidazolinyl)phenyl Catalysts for Enantioselective C–H Functionalization with Ethyl Diazoacetate” Mace Weldy, N. Schafer, A. G.; Owens, C. P.; Herting, C. J.; Varela- Alvarez, A.; Chen, S.; Niemeyer, Z.; Musaev, D. J.; Sigman, M. S.; Davies, H. M. L.; Blakey, S. B. Chem. Sci. 2016, 7, 3142 DOI:10.1039/C6SC00190D

32 About Ligand Design in Gold Carbene Complexes

Didier Bourissou Paul Sabatier University, 118 route de Narbonne, 31062 Toulouse cedex 9, FRANCE [email protected]

Gold carbenes are key intermediates in numerous catalytic transformations of great synthetic interest. In order to identify the factors dictating their reactivity, considerable efforts have been undertaken to characterize gold carbene complexes. A few stable carbenes have been isolated, mainly cationic Au(I) complexes featuring π-donating substituents at the carbene center. Recently, our group has been able to isolate new types of Au(I) carbene complexes thanks to a chelating (P,P) ligand.1,2 In addition, we have reported the first stable Au(III) carbene using a chelating (P,C) ligand and electron-withdrawing groups at the carbene center.3 It is striking to note that this Au(III) carbene complex displays nucleophilic, Schrock-type behaviour, whereas the known Au(I) carbene complexes are all electrophilic.

The synthesis, structure and reactivity of these species will be discussed in this presentation.

References 1. Joost, M.; Estévez L.; Mallet-Ladeira, S.; Miqueu, K.; Amgoune, A.; Bourissou, D. “Enhanced -Backdonation from Gold(I): Isolation of Original Carbonyl and Carbene Complexes” Angew. Chem. Int. Ed. 2014, 53, 14512‒14516. 2. Zeineddine, A.; Rekhroukh, F.; Mallet-Ladeira, S.; Miqueu, K.; Amgoune, A.; Bourissou, D. “Isolation of a Reactive Tricoordinate -oxo gold carbene complex” Angew. Chem. Int. Ed. 2018, 57, 1306‒1310. 3. Pujol, A.; Lafage, M.; Rekhroukh, F.; Saffon-Merceron, N.; Amgoune, A.; Bourissou, D.; Nebra, N.; Boutignon, M.; Mézailles, N. “A Nucleophilic Gold(III) Carbene Complex” Angew. Chem. Int. Ed. 2017, 56, 12264‒12267.

33

CURRICULUM VITAE – Didier Bourissou

CNRS Research Director Laboratoire Hétérochimie Fondamentale et Appliquée, Paul Sabatier University, 118 route de Narbonne, 31062 Toulouse cedex 9, FRANCE Tel: +33 (0)5 6155 6803 Email: [email protected] Homepage: https://lhfa.cnrs.fr/index.php/en/teams/lbpb-en/accueil-lbpb-en

Scientific Vita Since 2006 CNRS Research Director, Paul Sabatier University (Toulouse), Laboratoire Hétérochimie Fondamentale et Appliquée 2006-2018 Associate Professor, Ecole Polytechnique (Palaiseau) 1998-2006 CNRS Research Associate, Paul Sabatier University (Toulouse), Laboratoire Hétérochimie Fondamentale et Appliquée

Research Field Main group chemistry, bifunctional ligands, coordination chemistry, highly reactive species, new bonding modes and reactivity patterns, small molecule activation, catalysis, biodegradable polymers

Selected Awards and Recognition 2018 Award of the Organic Chemistry Division of the French Chemical Society 2017 Prime d’Excellence Scientifique from the CNRS 2016 Silver Medal from the CNRS 2013 Distinguished Junior Member of the French Chemical Society 2012 Prime d’Excellence Scientifique from the CNRS 2011 Experienced researcher fellowship from the Alexander von Humboldt Foundation 2009 Prime d’Excellence Scientifique from the CNRS 2009 Acros Award from the French Chemical Society 2006 Clavel Lespieau Award from the French Academy of Sciences 2005 Bronze Medal from the CNRS 1999 Dina Surdin Award from the French Chemical Society

Representative Publications 1. Rigoulet, M.; Massou, S.; Sosa Carrizo, E. D.; Mallet-Ladeira, S.; Amgoune, A.; Miqueu, K.; Bourissou, D. “ Evidence for Genuine Hydrogen Bonding in Gold(I) Complexes” Proc. Natl. Acad. Sci. U.S.A. 2019, 116, 46–51. 2. Joost, M.; Amgoune, A.; Bourissou, D. “Reactivity of Gold Complexes towards Elementary Organometallic Reactions” Angew. Chem. Int. Ed. 2015, 54, 15022–15045. 3. Bouhadir, G.; Bourissou, D. “Complexes of ambiphilic ligands: reactivity and catalytic applications” Chem. Soc. Rev. 2016, 45, 1065–1079. 4. Amgoune, A.; Bourissou, D. “-Acceptor, Z-type Ligands for Transition Metals” Chem. Commun. 2011, 47, 859–871.

34 Directed Evolution to Expand Nature’s Catalytic Repertoire Kai Chen Prof. Frances H. Arnold group, Division of Chemistry and Chemical Engineering California Institute of Technology, Pasadena, CA 91125, USA Email: [email protected]

Enzymes, nature’s catalytic workhorses, are capable of accelerating chemical transformations by orders of magnitude while simultaneously exerting exquisite control over selectivity. Readily produced from renewable resources and earth-abundant metal ions and functioning under ambient conditions, they are also ideal candidates for sustainable synthesis. Additionally, enzymes’ activity and selectivity can be genetically tuned using a powerful protein engineering strategy – directed evolution. All these features make biocatalysis a compelling alternative to metallo- or organo-catalysis for synthetic purposes.

Cytochrome P450s catalyze an astonishing array of oxidative reactions, including C‒H hydroxylation, olefin epoxidation, heteroatom oxidation and others, by utilizing high-valent iron- oxo species. By mimicking these highly reactive and versatile metallo-intermediates structurally and functionally, the Arnold group has been repurposing heme-dependent proteins to perform non-natural carbene and nitrene-transfer chemistries. Our work since 2013 has shown that hemeproteins can be evolved to accommodate iron-carbene or -nitrene intermediates and enable highly selective and efficient carbene- or nitrene-transfer reactions, such as cyclopropanation, aziridination, C‒H alkylation, C‒H amination and more. These newly developed biocatalytic transformations have significantly expanded the chemical space accessible to the biological world.

References 1. Coelho, P. S.; Brustad, E. M.; Kannan, A.; Arnold, F. H. Olefin cyclopropanation via carbene transfer catalyzed by engineered cytochrome P450 enzymes. Science 339, 307–310 (2013). 2. Chen, K.; Huang, X.; Kan, S. B. J.; Zhang, R. K.; Arnold, F. H. Enzymatic construction of highly strained carbocycles. Science 360, 71–75 (2018). 3. Zhang, R. K.; Chen, K.; Huang, X.; Wohlschlager, L.; Renata, H.; Arnold, F. H. Enzymatic assembly of carbon–carbon bonds via iron-catalysed sp3 C–H functionalization. Nature 565, 67–72 (2019). 4. Kan, S. B. J.; Lewis, R. D.; Chen, K.; Arnold, F. H. Directed evolution of cytochrome c for carbon–silicon bond formation: Bringing silicon to life. Science 354, 1048–1051 (2016). 5. Kan, S. B. J.; Huang, X.; Gumulya, Y.; Chen, K.; Arnold, F. H. Genetically programmed chiral organoborane synthesis. Nature 552, 132–136 (2017). 6. Prier, C. K.; Zhang, R. K.; Buller, A. R.; Brinkmann-Chen, S.; Arnold, F. H. Enantioselective, intermolecular benzylic C–H amination catalysed by an engineered iron- haem enzyme. Nat. Chem. 9, 629–634 (2017). 7. Cho, I.; Jia, Z.-J.; Arnold, F. H. Site-selective enzymatic C–H amidation for synthesis of diverse lactams. Science 364, 575–578 (2019). 35

CURRICULUM VITAE – Kai Chen

Ph.D. Candidate in Chemistry Prof. Frances H. Arnold group, Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA Tel: 001 (609) 937-7147 Email: [email protected] Arnold group website: http://fhalab.caltech.edu

Scientific Vita Since 2015 Ph.D. Candidate in Chemistry, Division of Chemistry and Chemical Engineering, California Institute of Technology, USA 2012-2015 Scientific research associate, Department of Chemistry, Zhejiang University, China 2008-2012 B.S. in Chemistry, Department of Chemistry, Zhejiang University, China

Research Field Directed evolution, enzyme catalysis, biocatalytic carbene chemistry, synthetic methodology, transition metal catalysis, C‒H activation/functionalization

Selected Awards and Recognition 2009 Second-Class Academic Outstanding Scholarship (Top 10%) 2010 First-Class Academic Outstanding Scholarship (Top 2%) 2010 National Scholarship (#1 in the Department of Chemistry) 2011 Second-Class Academic Outstanding Scholarship (Top 10%) 2012 Outstanding Graduation Thesis (Top 5%) 2016 Grand Prize of 2016 Dow Sustainability Innovation Student Challenge Award 2018 Resnick Fellowship (Caltech)

Representative Publications 1. Chen, K.; Huang, X.; Kan, S. B. J.; Zhang, R. K.; Arnold, F. H. Enzymatic construction of highly strained carbocycles. Science 360, 71–75 (2018). 2. Chen, K.; Zhang, S.-Q.; Brandenberg, O. F.; Hong, X.; Arnold, F. H. Alternate heme ligation steers activity and selectivity in engineered cytochrome P450-catalyzed carbene transfer reactions. J. Am. Chem. Soc. 140, 16402–16407 (2018). 3. Zhang, R. K.; Chen, K.; Huang, X.; Wohlschlager, L.; Renata, H.; Arnold, F. H. Enzymatic assembly of carbon–carbon bonds via iron-catalysed sp3 C–H functionalization. Nature 565, 67–72 (2019). 4. Kan, S. B. J.; Lewis, R. D.; Chen, K.; Arnold, F. H. Directed evolution of cytochrome c for carbon– silicon bond formation: Bringing silicon to life. Science 354, 1048–1051 (2016). 5. Kan, S. B. J.; Huang, X.; Gumulya, Y.; Chen, K.; Arnold, F. H. Genetically programmed chiral organoborane synthesis. Nature 552, 132–136 (2017). 6. Chen, K.; Shi, B.-F. Sulfonamide-promoted palladium(II)-catalyzed alkylation of unactivated methylene C(sp3)–H bonds with alkyl iodides. Angew. Chem. Int. Ed. 53, 11950–11954 (2014). 7. Chen, K.; Hu, F.; Zhang, S.-Q.; Shi, B.-F. Pd(II)-catalyzed alkylation of unactivated C(sp3)–H bonds: Efficient synthesis of optically active unnatural α-amino acids. Chem. Sci. 4, 3906–3911 (2013).

36 Adventures in Exploiting Diazoacetates in Metal-Catalyzed and Thermal Rearrangements to Biologically Relevant Heterocycles Doug E. Frantz Department of Chemistry, University of Texas at San Antonio, San Antonio, Texas 78249, USA [email protected]

Diazoacetates have been exploited in numerous transformations with a large majority promoted by the use of transition metal catalysts that proceed via well-established metal-carbene intermediates. Yet, their inherent reactivity can also be harnessed through non-metal promoted pathways where the diazo functionality is retained to access nitrogen-based heterocycles such as pyrazoles. Our group became interested in the use of diazoacetates in both metal-catalyzed and non-metal thermal pathways due to our ability to easily access densely functionalize vinyl diazoacetates from stereodefined enol triflates. With these building blocks in hand from readily available precursors, we have identified three productive pathways (one metal-catalyzed, two thermal processes) that have led to the synthesis of furans, butenolides and pyrazoles. During the course of our studies, we also discovered the first example of the all-carbon aromatic Cope rearrangement that will also be discussed.

Synthesis of substituted furans and butenolides from vinyl diazoacetates

Synthesis of substituted pyrazoles from in situ generate vinyl diazoacetates

Discovery of the all-carbon aromatic Cope rearrangement

References 1. El Arba, M.; Dibrell, S. E.; Meece. F.; Frantz, D. E. “Ru-Catalyzed Synthesis of Substituted Furans from Diazoacetates” Org. Lett. 2018, 20, 5886.

2. Babinksi, D. J.; Bao, X.; El Arba, M.; Chen, B.; Hrovat, D. A.; Borden, W. T.; Frantz, D. E. “Synchronized Aromaticity as an Enthalpic Driving Force for the Aromatic Cope Rearrangement” J. Am. Chem. Soc. 2012, 134, 16139.

3. Babinski, D. J.; Aguilar, H. A.; Still, R.; Frantz, D. E. “Synthesis of substituted pyrazoles via tandem cross-coupling/electrocyclization of enol triflates and diazoacetates.” J. Org. Chem. 2011, 76, 5915

37

CURRICULUM VITAE – Doug E. Frantz

Professor of Chemistry The Max and Minnie Tomerlin Voelcker Distinguished Professor of Chemistry, Department of Chemistry, The University of Texas at San Antonio, San Antonio, Texas 78249, USA Tel: 001 (210) 458-7048 Email: [email protected] Homepage: https://chemistry.utsa.edu/frantzlab/

Scientific Vita Since 2009 The University of Texas at San Antonio: Professor (2016), Associate Professor (2013), Assistant Professor (2009) Since 2010 University of Texas Health San Antonio, Adjoint Professor, Department of Biochemistry 2005-2009 The University of Texas Southwestern Medical Center, Director of the Synthetic Chemistry Core Facility, Department of Biochemistry 2003-2005 Research Fellow, Merck & Co., Department of Process Research 2000-2003 Senior Research Scientist, Merck & Co., Department of Process Research

Research Field Asymmetric catalysis, synthetic methodology, medicinal chemistry, drug discovery and development

Selected Awards and Recognition 2017 Thieme Chemistry Journal Awardee 2015 Organizer, Co-Chair and Co-Founder of the Biannual TexSyn Conference in Texas 2014 Eli Lilly & Co. Outstanding Open Innovation Drug Discovery Collaborator Award 2014 Co-Chair, 2014 Gordon Research Conference on Organic Reactions and Processes 2011 UTSA President’s Distinguished Research Award for Tenure-Track Faculty 2010 Max and Minnie Tomerlin Voelcker Fund Young Investigator Award

Representative Publications 1. Neff, R. K.; Frantz, D. E. “The Cationic Alkynyl Heck Reaction Towards Substituted Allenes Using BobCat: A New Hybrid Pd(0)-Catalyst Incorporating a Water-Soluble dba ligand” J. Am. Chem. Soc. 2018 140, 17248.

2. Stevens, J. M.; Parra Rivera, A.C.; Dixon, D. D.; Beutner, G. L.; Delmonte, A.; Frantz D. E.; Janey, J.M.; Paulson, J.; Talley, M. “Direct Lewis Acid-Catalyzed Conversion of Enantioenriched N-Acyl Oxazolidinones to Chiral Esters, Amides and Acids.” Accepted as a Featured Article in The Journal of Organic Chemistry 2018, 83, 14245.

3. El Arba, M.; Dibrell, S. E.; Meece. F.; Frantz, D. E. “Ru-Catalyzed Synthesis of Substituted Furans from Diazoacetates” Org. Lett. 2018, 20, 5886.

4. Babinksi, D. J.; Bao, X.; El Arba, M.; Chen, B.; Hrovat, D. A.; Borden, W. T.; Frantz, D. E. “Synchronized Aromaticity as an Enthalpic Driving Force for the Aromatic Cope Rearrangement” J. Am. Chem. Soc. 2012, 134, 16139.

5. Babinski, D. J.; Aguilar, H. A.; Still, R.; Frantz, D. E. “Synthesis of substituted pyrazoles via tandem cross-coupling/electrocyclization of enol triflates and diazoacetates.” J. Org. Chem. 2011, 76, 5915

38 Nucleophilic Late Transition Metal Carbene Complexes: From Reactive Species to Cooperative Bond Activation Reactions

Viktoria H. Gessner Faculty of Chemistry and Biochemistry, Ruhr-University of Bochum, 44801 Bochum, Germany [email protected]

Despite the ubiquity of carbene complexes in organometallic chemistry and catalysis, nucleophilic carbene complexes of late transition metals remain rare and poorly studied species. In general, these complexes represent a special class of carbenes, whose bonding situation often does not fit into the classical Fischer and Schrock classification pattern. Here, the metal carbon bond is usually highly polarized towards the carbon end and best described by two dative bonds from the carbon to the metal center. This renders these compounds highly reactive and hence difficult to isolate, particularly without the help of further supporting donor side-arms. However, this unique bonding situation also promises new properties compared to classical carbene complexes, which may give rise to new transformations and applictions.1

In recent years, we have studied the potential of these carbene species in cooperative bond activation reactions. These activation processes proceed via addition of element-hydrogen bonds directly across the metal carbon double bond. Until now, a variety of E-H bonds of different polarity have been activated and first reversible transformations have been accomplished, based on which first catalytic applications have been realized.2,3 In this presentation, we discuss synthetic methods to isolate nucleophilic late transition metal carbene complexes as well as approaches to fine-tune their electronic properties for reversible bond activation reactions.4 Recent research endeavors towards applications in catalytic (de)-hydrogenation and transfer hydrogenation reactions will be presented.

References 1. Feichtner, K.-S.; Gessner, V. H. “Cooperative Bond Activation Reactions with Carbene Complexes” Chem. Commun. 2018, 54, 6540–6553. And references therein. 2. Weismann, J.; Gessner, V. H. “Si‒H Activation by means of Metal Ligand Cooperation in a Methandiide Derived Carbene Complex” Chem. Commun. 2015, 51, 14909–14912. 3. Becker, J.; Model T.; Gessner, V. H. “A Methandiide as Non-Innocent Ligand in Carbene Complexes: From the Electronic Structure to Bond Activation Reactions and Cooperative Catalysis” Chem. Eur. J. 2014, 20, 11295–11299. 4. Scherpf, T.; Wirth, R.; Molitor, S.; Feichtner, K.-S.; Gessner, V. H. “Bridging the Gap between Bisylides and Methandiides: Isolation, Reactivity and Electronic Structure of a Free Yldiide” Angew. Chem. Int. Ed. 2015, 54, 8542–8546.

39

CURRICULUM VITAE – Viktoria H. Gessner

Professor of Inorganic Chemistry Chair of Inorganic Chemistry II, Department of Chemistry and Biochemistry, Ruhr-University Bochum, 44801 Bochum, Germany Tel: 049 (234) 32-24174 Email: [email protected] Homepage: https://www.ruhr-uni-bochum.de/ac2/index.html.en

Scientific Vita Since 2016 Ruhr-University Bochum, Germany, Chair of Inorganic Chemistry II, Faculty of Chemistry and Biochemistry 2011-2016 University of Würzburg, Independent Researcher, Emmy-Noether group leader, habilitation in inorganic chemistry 2009-2010 University of California, Berkeley, USA, Postdoctoral fellow with Prof. Dr. T. Don Tilley 2007-2009 University of Dortmund, Germany, PhD with Prof. Dr. Carsten Strohmann 2004-2007 Undergraduate studies at University of Würzburg, Germany 2002-2004 Undergraduate studies at University of Marburg, Germany

Research Field Ylide chemistry, metal carbene chemistry, homogenous catalysis, ligand design, metal ligand cooperativity.

Selected Awards and Recognition 2007 PhD Fellowship of the Chemical Industry Fund 2008 European Young Chemist Award (Silver medal) 2009 PhD Award of the TU Dortmund 2009 Feodor Lynen Postdoc Fellowship of the Alexander von Humboldt Foundation 2010 IUPAC Prize for young researchers in chemistry 2012 Helene Lange Award of the University of Oldenburg and of the EWE Foundation 2012 Emmy-Noether Grant of the German Science Foundation 2013 Award of the Dr. Otto-Röhm-Gedächtnisstiftung 2014 Röntgen Award for young scientists of the University of Würzburg 2015 ADUC Award for habilitands 2014 2016 Starting grant of the European Research Council (ERC) 2016 Thieme Journal Award

Representative Publications 1. Mohapatra, C.; Scharf, L. T.; Scherpf, T.; Mallick, B.; Feichtner, K.-S.; Schwarz, C.; Gessner, V. H. „Isolation of a Diylide-Stabilized Stannylene and Germylene: Enhanced Donor Strength through Coplanar Lone Pair Alignment” Angew. Chem. Int. Ed. 2019, 58, 7459-7463. 2. Scherpf, T.; Schwarz, C.; Scharf, L. T.; Zur, J.-A.; Helbig, A.; Gessner, V. H. “Ylide-functionalized phosphines: Strong Donor Ligands for Homogenous Catalysis” Angew. Chem. Int. Ed. 2018, 57, 12859. 3. Feichtner, K.-S.; Gessner, V. H. “Cooperative Bond Activation Reactions with Carbene Complexes” Chem. Commun. 2018, 54, 6540-6553. 4. Molitor, S.; Gessner, V. H. “Alkali Metal Carbenoids: A Case of Higher Stability of the Heavier Congeners” Angew. Chem. Int. Ed. 2016, 55, 7712–7716.

40 Reactivity of diazo compounds under visible-light irradiation

Dorota Gryko Institute of Organic Chemistry PAS, Kasprzaka 44/52, 01-224 Warsaw, Poland [email protected]

Application of visible light in organic transformations is of growing interest. In this line, both elimination of expensive and toxic metal catalysts and application of visible light for activation of diazo compounds is extremely attractive. Photochemical reactions engaging diazo compounds have been investigated over the years.1 Although UV-light-induced carbene generation is well known in diazo chemistry, only recently it became clear that introduction of a donor group to diazoacetates enables their photolysis under blue light irradiation.2 We have shown that visible light induced decomposition of diazo compounds allows reaction with various propargyl reagents giving allenes through the [2,3]-sigmatropic rearrangement. But α-diazo compounds can be also involved in photoredox reactions as efficient alkylating reagents of carbonyl compounds3,4,5 On the other hand photoalkylation of electron-rich aromatic compounds with diazo esters leads to C2 alkylation of indoles and pyrroles.6 While for diazo compounds exhibiting strong absorption within the wavelength region of the light used for irradiation, the regioselectivity of the alkylation reaction alters from C2 to C3.

References 1. Ciszewski, Ł. W.; Rybicka-Jasińska, K.; Gryko, D. “Recent developments in photochemical reactions of diazo compounds” Org. Biomol. Chem. 2019, 17, 432-448. 2. Jurberg, I. D.; Davies, H. M. L. “Blue light-promoted photolysis of aryldiazoacetates” Chem. Sci. 2018, 9, 5112-5118. 3. Rybicka-Jasińska, K.; Shan, W.; Zawada, K.; Kadish, K. M.; Gryko D. “Porphyrins as Photoredox Catalysts - Experimental and Theoretical studies” J. Am. Chem. Soc. 2016, 138, 15451-15458. 4. Rybicka-Jasińska, K.; Orłowska, K; Karczewski, M; Zawada, K; Gryko, D. “Why Cyclopropanation is not Involved in Photoinduced α‐Alkylation of Ketones with Diazo Compounds” Eur. J. Chem. 2018, 47, 6634-6642. 5. Huang, X.; Webster, R. D.; Harms, K.; Meggers, E. “Asymmetric Catalysis with Organic Azides and Diazo Compounds Initiated by Photoinduced Electron Transfer” J. Am. Chem. Soc. 2016, 138, 12636-12642. 6. Ciszewski, Ł. W.; Durka, J.; Gryko, D. “Photocatalytic Alkylation of Pyrroles and Indoles with α-Diazo Esters” Org. Lett., 2019, 21, 7028-7032.

41 CURRICULUM VITAE – Dorota Gryko

Professor of Chemistry Institute of Organic Chemistry Polish Academy of Sciences Kasprzaka 44/52, 01-224 Warsaw, Poland Tel: +48 (22) 458-4196 Email: [email protected] Homepage: https://ww2.icho.edu.pl/gryko_group/

Scientific Vita Since 2016 Director of the PhD Studies Since-2015 Institute of Organic Chemistry, PAS; Full Professor 1997-2015 Titular Professor distinction granted by the President of Poland 2010-2008 Institute of Organic Chemistry, PAS; Professor 1984-2008 Institute of Organic Chemistry, habilitation 1994-1997 Institute of Organic Chemistry, PAS; Ph.D. studies. Research Field photocatalysis, reactions of diazo compounds, Co-catalysis, B12 chemistry, porphyrin catalysis, synthetic methodology

Selected Awards and Recognition 1998 Prime Minister Award for the best Ph.D. 2020 Marii Curie’s Award for a Collaborative research

Representative Publications 1. Ciszewski, Ł.W.; Rybicka-Jasińska, K.; Gryko, D. “Recent developments in photochemical reactions of diazo compounds” Org. Bio. Chem. 2019, 17, 432-448 2. Rybicka-Jasińska, K.; Shan, W.; Zawada, K.; Kadish, K.; Gryko, D. “Porphyrins as Photoredox Catalysts - Experimental and Theoretical studies” J. Am. Chem. Soc., 2016, 138, 15451-15458. 3. Ociepa, M.; Turkowska, J.; Gryko, D. “Redox-activated amines in C(sp3)-C(sp) and C(sp3)-C(sp)2 bond formation enabled by metal-free photoredox catalysis” ACS Catalysis, 2018, 8, 11362-11367. 4. Ciszewski, Ł. W.; Durka, J.; Gryko, D. “Photocatalytic Alkylation of Pyrroles and Indoles with α- Diazo Esters” Org. Lett., 2019, 21, 7028-7032. 5. Braselmann, E.; Wierzba, A. J.; Polaski, J. T.; Chromiński, M.; Holmes, Z, E.; Hung, S.; Batan, D.; Wheeler, J. R.; Parker, R.; Jimenez, R.; Gryko, D.; Batey, R. T.; Palmer, A. E. “A multicolor riboswitch-based platform for imaging of RNA in live mammalian cells” Nat. Chem. Bio., 2018, 14, 964-971.

42 Transition Metal and Free Difluorocarbenes: Syntheses of Fluorinated Cyclopentanone Derivatives

Junji Ichikawa Division of Chemistry, Pure and Applied Sciences, University of Tsukuba, Tsukuba, Japan [email protected]

Difluorocarbene (:CF2) is a synthetically useful species for the introduction of a difluoromethylene group into organic molecules. Although useful, the generation of difluorocarbene may cause its dimerization and/or overreactions. We reexamined the generation of difluorocarbene starting from trimethylsilyl 2,2-difluoro-2-fluorosulfonylacetate (TFDA) and sodium bromodifluoroacetate by the use of metal catalysts and organocatalysts. Thus, we have achieved the controlled generation of metal and free difluorocarbenes under mild conditions by choosing the appropriate catalyst such as Ni and Cu halides and Proton Sponge (PS). Transition metal difluorocarbene complexes (LnM=CF2) are highly promising intermediates for the synthesis of fluorine-containing compounds. Despite their potential utility, however, only a limited number of reactions of difluorocarbene complexes have been reported in the past. Recently, we have accomplished the regioselective syntheses of α- and β-, di- and mono- fluorinated cyclopentanone derivatives starting from silyl dienol ethers by using Ni1) and Cu2) difluorocarbene complexes. Furthermore, difluorocyclopropanation of silyl dienol ethers with free difluorocarbene, followed by ring opening gave 1-fluorovinyl vinyl ketones, whose Nazarov cyclizations afforded α-fluorocyclopentanones regioselectively.3) Thus, biologically promising di- and mono-fluorocyclopentenone derivatives are readily synthe- sized starting from silyl dienol ethers by choosing the appropriate CF insertion protocols. 4) 2 t OSiMe2 Bu O OH " Ni CF2 " F F F O F F FSO2CF2CO2SiMe3 R R cat. Ni(II) R t t OSiMe2 Bu O OSiMe2 Bu " Cu CF2 "

R BrCF CO Na R 2 2 F cat. Cu(I) F F R O O

" :CF " 2 F Me3SiB(OTf)4 F – R i) TFDA, cat. PS, ii) cat. F R References 1. Aono, T.; Sasagawa, H.; Fuchibe, K.; Ichikawa, J. “Regioselective Synthesis of α,α- Difluorocyclopentanone Derivatives: Domino Nickel-Catalyzed Difluorocyclopropanation /Ring Expansion Sequence of Silyl Dienol Ethers” Org. Lett. 2015, 17, 5736–5739. 2. Fuchibe, K.; Aono, T.; Hu, J.; Ichikawa, J. “Copper(I)-Catalyzed [4 + 1] Cycloaddition of Silyl Dienol Ethers with Sodium Bromodifluoroacetate: Access to β,β-Difluorocyclo- pentanone Derivatives” Org. Lett. 2016, 18, 4502–4505. 3. Fuchibe, K.; Takayama, R.; Yokoyama, T.; Ichikawa, J. “Regioselective Synthesis of α- Fluorinated Cyclopentenones by Organocatalytic Difluorocyclopropanation and Fluorine- Directed and Fluorine-Activated Nazarov Cyclization”, Chem. Eur. J. 2017, 23, 2831–2838. 4. Fuchibe, K.; Takayama, R.; Aono, T.; Hu, J.; Hidano, T.; Sasagawa, H.; Fujiwara, M.; Miyazaki, S.; Nadano, R.; Ichikawa, J. “Regioselective Syntheses of Fluorinated Cyclopentanone Derivatives: Ring Construction Strategy Using Transition-Metal– Difluorocarbene Complexes and Free Difluorocarbene” Synthesis 2018, 50, 514–528. 43

CURRICULUM VITAE – Junji Ichikawa

Professor of Chemistry University of Tsukuba, Division of Chemistry, Faculty of Pure and Applied Sciences, Tsukuba, Ibaraki, 305-8571, JAPAN Tel: (+81) 29-853-4237 Email: [email protected] Homepage: http://www.chem.tsukuba.ac.jp/junji/

Scientific Vita Since 2007 Professor, Division of Chemistry, Faculty of Pure and Applied Sciences, University of Tsukuba 2004 Visiting Professor, Department of Chemistry, University Louis Pasteur 1999-2007 Associate Professor, Department of Chemistry, Graduate School of Science, The University of Tokyo 1993-1999 Associate Professor, Department of Applied Chemistry, Kyushu Institute of Technology 1991-1993 Lecturer, Department of Applied Chemistry, Kyushu Institute of Technology 1989-1990 Research Associate at Department of Chemistry, Harvard University (USA) 1985-1991 Assistant Professor, Institute of Advanced Material Study, Kyushu University 1986 Ph.D. in chemistry, Department of Chemistry, Graduate School of Science, The University of Tokyo 1981 B.S. in chemistry, Department of Chemistry, Faculty of Science, The University of Tokyo

Research Field Synthetic methodology, fluorine chemistry, organometallic chemistry, carbocation chemistry, carbene chemistry, reactions of fluoroalkenes

Selected Awards and Recognition 1991 The Nippon Kasei Chemical Award in Synthetic Organic Chemistry, Japan 1994 Progress Award in Synthetic Organic Chemistry, Japan 1996 The Daiichi Pharmaceutical Award in Synthetic Organic Chemistry, Japan 2015 The Chemical Society of Japan Award for Creative Work 2018 Synthetic Organic Chemistry Award, Japan

Representative Publications 1. Fujita, T.; Fuchibe, K.; Ichikawa, J. “Transition Metal-Mediated and -Catalyzed C–F Bond Activation via Fluorine Elimination” Angew. Chem. Int. Ed. 2019, 58, 390–402. 2. Takahashi, I.; Fujita, T.; Shoji, N.; Ichikawa, J. “Brønsted Acid-Catalysed Hydroarylation of Unactivated Alkynes in Fluoroalcohol–Hydrocarbon Biphasic System: Construction of Phenanthrene Frameworks” Chem. Commun. 2019, 55, 9267–9270. 3. Fuchibe, K.; Oki, R.; Hatta, H.; Ichikawa, J. “Single C–F Bond Activation of the CF3 Group with a Lewis Acid: CF3-Cyclopropanes as Versatile 4,4-Difluorohomoallylating Agents” Chem. Eur. J. 2018, 24, 17932–17935. 4. Fujita, T.; Morioka, R.; Arita, T.; Ichikawa, J. “sp3 Carbon–Fluorine Bond Activation in 2,2- Difluorohomoallylic Alcohols via Nucleophilic 5-endo-trig Cyclisation: Synthesis of 3-Fluorinated Furan Derivatives”, Chem. Commun. 2018, 54, 12938–12941. 5. Fuchibe, K.; Hatta, H.; Oh, K.; Oki, R.; Ichikawa, J. “Lewis Acid-Promoted Single C–F Bond Activation of the CF3 Group: SN1'-type 3,3-Difluoroallylation of Arenes with 2-Trifluoromethyl-1- alkenes” Angew. Chem. Int. Ed. 2017, 56, 5890–5893. 6. Fuchibe, K.; Abe, M.; Oh, K.; Ichikawa, J. “Preparation of 1,1-Difluoroallenes by Difluorovinylidenation of Carbonyl Compounds” Org. Synth. 2016, 93, 352–366. 7. Ichitsuka, T.; Fujita, T.; Arita, T.; Ichikawa, J. “Double C–F Bond Activation via β-Fluorine Elimination: Nickel-Mediated [3+2] Cycloaddition of 2-Trifluoromethyl-1-alkenes with Alkynes” Angew. Chem. Int. Ed. 2014, 53, 7564–7568. 44 Dirhodium Artificial Metalloenzymes: Selective Catalysis, Directed Evolution, Structure, and Dynamics

Jared C. Lewis Department of Chemistry, Indiana University, Bloomington, IN 47401, USA [email protected]

Artificial metalloenzymes (ArMs) are hybrid catalysts comprised of a synthetic organometallic cofactor linked to a protein scaffold. The sizes, shapes, and dynamics of these systems provide exciting possibilities for manipulating molecules and reactivity. Realizing the catalytic potential of ArMs, however, requires a detailed understanding of their parts and how those parts interact with one another. In this talk, I will discuss research aimed at evolving dirhodium ArMs and understanding the impact of prolyl oligopeptidase (POP) structure and dynamics on dirhodium catalysis within the POP interior.1-3

References 1. Lewis, J. C.* Beyond the Second Coordination Sphere: Engineering Dirhodium Artificial Metalloenzymes to Enable Protein Control of Transition Metal Catalysis. Accounts of Chemical Research. 2019, 52, 576-584. 2. Yang, H.; Swartz, A. M.; Srivastava, P.; Ellis-Guardiola, K.; Park, H. J.; Upp, D.; Belsare, K.; Lee, G.; Zhang, C.; Moellering, R. E.; Lewis, J. C.* Evolving Artificial Metalloenzyme Selectivity via Random Mutagenesis. Nat. Chem. 2018, 10, 318-324. 3. Srivastava, P.; Yang, H.; Ellis-Guardiola, K.; Lewis, J. C.* Engineering a Dirhodium Artificial Metalloenzyme for Selective Olefin Cyclopropanation. Nat. Commun. 2015, 6, 7789.

45

CURRICULUM VITAE – Jared C. Lewis

Associate Professor of Chemistry Department of Chemistry, Indiana University Bloomington, IN 47401, USA Tel: 001 (812) 856-0454 Email: [email protected] Homepage: https://www.indiana.edu/~lewisgrp/

Scientific Vita Since 2018 Indiana University, Associate Professor, Department of Chemistry 2011-2017 University of Chicago, Assistant Professor, Department of Chemistry

Research Field Catalysis, Artificial Metalloenzymes, Directed Evolution, Protein Engineering, Chemical Biology

Selected Awards and Recognition 2019 Novartis Chemistry Lectureship 2016 Dreyfus Teacher-Scholar Award 2015 Ed Stiefel Young Investigator Award (given by the Metals in Biology GRC) 2014 NSF CAREER Award 2013 Thieme Chemistry Journal Award 2013 CBC Catalyst Award 2011 David and Lucile Packard Foundation Fellowship in Science and Engineering 2011 Searle Scholar Award 2010 NIH Pathways to Independence Award

Representative Publications 1. Ellis-Guardiola, K.; Rui, H.; Beckner, R. L.; Park, H.-J.; Srivastava, P.; Roux, B.; Sukumar, N.; Lewis, J. C.* Crystal Structure and Conformational Dynamics of Pyrococcus furiosus Prolyl Oligopeptidase. Biochemistry, 2019, 58, 1616-1626. 2. Yang, H.; Swartz, A. M.; Srivastava, P.; Ellis-Guardiola, K.; Park, H. J.; Upp, D.; Belsare, K.; Lee, G.; Gu, Y.; Zhang, C.; Moellering, R. E.; Lewis, J. C.* Evolving Artificial Metalloenzyme Selectivity via Random Mutagenesis. Nat. Chem. 2018, 10, 318-324. 3. Andorfer, M. C.; Park, H. J.; Vergara-Coll, J.; Lewis, J. C.* Directed Evolution of RebH for Catalyst-Controlled Halogenation of Indole C-H Bonds. Chem. Sci. 2016, 7, 3720-3729. 4. Gu, Y.; Ellis-Guardiola, K.; Srivastava, P.; Lewis, J. C.* Preparation, Characterization, and Reactivity of a Photocatalytic Artificial Enzyme. ChemBioChem. 2015, 16, 1880-1883. 5. Payne, J. T.; Poor, C. B.; Lewis, J. C.* Directed Evolution of RebH for Site Selective Halogenation of Large, Biologically Active Molecules. Angew. Chem. Int. Ed. 2015, 54, 4226-4230.

46 Synthetic and stereochemical aspects of intramolecular C–H insertions with α-diazocarbonyl compounds

Anita R. Maguire School of Chemistry and School of Pharmacy, Analytical and Biological Chemistry Research Facility, Synthesis and Solid State Pharmaceutical Centre, University College Cork, Cork, Ireland [email protected]

Metal-catalyzed transformations of α-diazocarbonyl compounds have a proven track record in organic synthesis, allowing the rapid build-up of molecular complexity, often in a highly chemo-, regio-, and stereoselective manner, under mild conditions.1 One such reaction that has attracted attention is the intramolecular C–H insertion which leads to formation of carbocyclic and heterocyclic compounds. The reactions of α-diazosulfones and related compounds in the presence of copper(bisoxazoline) or rhodium carboxylate catalysts lead efficiently to cyclopentanones, sulfolanes, thiopyrans, sultones, and lactams.2 The selectivity patterns seen in the copper- and rhodium-catalyzed reactions are often complementary.

Despite the versatility of metal-carbene chemistry at a laboratory scale, there are challenges in extending this to large scale synthesis for safety reasons. Continuous flow processing can enable the use of this chemistry at large scale by eliminating the need to isolate and handle high- energy species. We have established methods for in situ generation of tosyl and mesyl azide, coupled with their direct application to diazo transfer, and successfully telescoped this with subsequent carbene reactions.3

References 1. Ford, A.; Miel, H.; Ring, A.; Slattery, C. N.; Maguire, A. R.; McKervey, M. A. Chem. Rev. 2015, 115, 9981–10080.. 2. a) Flynn, C. J.; Elcoate, C. J.; Lawrence, S. E.; Maguire, A. R. J. Am. Chem. Soc. 2010, 132, 1184–1185. b) Slattery C. N.; Maguire, A. R. Org. Biomol. Chem. 2011, 9, 667–669. c) Clarke, L.-A.; Ring, A.; Ford, A.; Sinha, A. S.; Lawrence S. E.; Maguire, A. R. Org. Biomol. Chem. 2014, 12, 7612–7628. d) Shiely, A. E.; Slattery, C. N.; Ford, A.; Eccles, K. S.; Lawrence, S. E.; Maguire, A. R. Org. Biomol. Chem. 2017, 15, 2609–2628. e) Shiely, A. E.; Clarke, L.-A.; Flynn, C. J.; Buckley, A. M.; Ford, A.; Lawrence S. E.; Maguire, A. R. Eur. J. Org. Chem. 2018, 2277–2289. f) . Brouder, T. A.; Slattery, C N. Ford, A.; Khandavilli, U. B. R.; Skořepová, E.; Eccles, K. S.; Lusi, M.; Lawrence, S. E.; Maguire, A. R. J. Org. Chem. 2019, 84, 7543–7563 3. a) Deadman, B. J.; O’Mahony, R. M.; Lynch, D.; Crowley, D. C.; Collins S. G.; Maguire, A. R. Org. Biomol. Chem. 2016, 14, 3423–3431. b) O’Mahony, R. M.; Lynch, D.; Hayes, H. L. D.; Ní Thuama, E.; Donnellan, P.; Jones, R. C.; Glennon, B.; Collins S. G.; Maguire, A. R. Eur. Org. Chem. 2017, 6533–6539. c) Crowley, D. C.; Lynch D.; Maguire, A. R. J. Org. Chem. 2018, 83, 3794. 47

CURRICULUM VITAE – Anita R Maguire

Vice President for Research & Innovation, Professor of Pharmaceutical Chemistry School of Chemistry and School of Pharmacy, University College Cork, College Road, Cork, Ireland Tel: +353 (21) 490-3500 / 3542 Email: [email protected] Homepage: http://publish.ucc.ie/researchprofiles/V001/amaguire

Scientific Vita 2011-2016 University of Bergen, Norway, Adjunct Professor, Department of Chemistry. University College Cork Since 2011 Vice President for Research & Innovation Since 2004 Inaugural holder of Professor of Pharmaceutical Chemistry Since 2002 Director, Analytical & Biological Chemistry Research Facility 2009-2010 Head of School of Pharmacy 2005-2007 Head of School of Chemistry 2003-2012 Member of the Governing Body of UCC 2002-2004 Associate Professor of Organic Chemistry 1991-2002 Lecturer in Organic Chemistry

Research Field Asymmetric synthesis - including transition metal catalysis and biocatalysis; Synthetic methodology - -diazocarbonyl compounds & organosulfur compounds in synthesis; Design and synthesis of bioactive compounds with pharmaceutical applications; Crystal engineering; Continuous flow processing.

Selected Awards and Recognition 2013 Fellow, Royal Society of Chemistry 2013 Fellow, Institute of Chemistry in Ireland 2014 Elected as a Member of the Royal Irish Academy 2015 Inaugural Chair, National Forum on Research Integrity 2018 Featured in RSC Themed Collection “Celebrating Excellence in Research; 100 Women of Chemistry” 2018 Eva Philbin Award, Institute of Chemistry of Ireland 2019 Vice President of the Royal Irish Academy

Representative Publications 1. Desymmetrization by Asymmetric Copper-Catalyzed Intramolecular C-H Insertion Reactions of - Diazo--oxosulfones, Brouder TA, Slattery CN, Ford A, Khandavilli UBR, Skorepova E, Eccles KS, Lusi M, Lawrence SE, Maguire AR, J. Org. Chem., 2019, 84, 7543-7563. 2. Copper-Mediated, Heterogeneous, Enantioselective Intramolecular Buchner Reactions of - Diazoketones Using Continuous Flow Processing, Crowley DC; Lynch D; Maguire AR, J. Org. Chem., 2018, 83, 3794-3805. 3. Synthesis of Guanine -Carboxy Nucleoside Phosphonate (G--CNP), a Direct Inhibitor of Multiple Viral DNA Polymerases, Maguire NM; Ford A; Balzarini J; Maguire AR, J. Org. Chem, 2018, 83, 10510-10517 4. Highly Enantioselective Intramolecular Copper Catalyzed C-H Insertion Reactions of - Diazosulfones, Flynn CJ, Elcoate CJ, Lawrence SE, Maguire AR, J. Am. Chem. Soc., 2010, 132, 1184–1185.

48 Late Transition Metal Terminal Imido Complexes for Catalysis

Dominik Munz Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Department for Chemistry and Pharmacy, Chair for Inorganic and General Chemistry, Egerlandstr. 1, 91058 Erlangen, Germany. [email protected]

Late transition metal complexes with formal multiple bonds to a nitrogen atom are powerful N- atom transfer reagents. These complexes become increasingly reactive with increasing d-elec- tron population. However, whereas such nitrene (i.e. open-shell) complexes have received a lot of attention in recent years, the closed-shell imido analogues remain largely unexplored. We propose d8 configured palladium- and gold terminal imido complexes as intermediates for CH bond functionalization, the hydrogenation of azides, reduction of nitro groups, and amination of double bonds. Following computational predictions, we isolated recently the first example of a terminal imido complex of palladium. This closed-shell complex shows an antagonal electronic structure to late transition metal carbene complexes: Whereas both are strongly polarized, the terminal imido complex is highly nucleophilic, whereas the carbene complexes are electrophilic.

C N Pd , H , CH, NH, OH bonds? Catalysis with RN3 2 N O SO Tol

In this lecture, I will report on the reactivity of this complex with H2, CO2, NH, OH and weak CH bonds. I will describe the detailed mechanism for the catalytic hydrogenation of azides and elucidate side reactions due to the formation of very reactive metal(0) intermediates. Eventually, I will discuss the synthesis of isoelectronic congeners of other metals.

References 1. For a recent highlight, see: Carsch, K. M.; DiMucci, I. M.; Iovan, D. A.; Li, A.; Zheng, S.-L.; Titus, C. J.; Lee, S. J.; Irwin, K. D.; Nordlund, D. L., Kyle M.; Betley, T. A. “Synthesis of a copper-supported triplet nitrene complex pertinent to copper-catalyzed amination” Science 2019, 365, 1138. For a review, see: Kuijpers, P. F.; van der Vlugt, J. I.; Schneider, S.; de Bruin, B. “Nitrene Radical Intermediates in Catalytic Synthesis“ Chem. Eur. J. 2017, 23, 13819. 2. Grünwald, A.; Orth, N.; Pöthig, A.; Heinemann, F. W.; Munz, D. “An Isolable Palladium Terminal Imido and Catalytic Implications” Angew. Chem. Int. Ed. 2018, 57, 16228. 3. Munz, D. “How to Tame a Palladium Terminal Oxo” Chem. Sci. 2018, 9, 1155. 4. Grünwald, A.; Munz, D. “How to Tame a Palladium Terminal Imido” J. Organomet. Chem. 2018, 864, 26. 5. Goodner, S. J.; Grünwald, A.; Heinemann, F. W.; Munz, D. ”Carbon Dioxide Activation by a Palladium Terminal Imido Complex” Austr. J. Chem. 2019, DOI: 10.1071/CH19323. 6. Submitted.

49

CURRICULUM VITAE – Dominik Munz

Junior Group Leader Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Department for Chemistry and Pharmacy, Chair for Inorganic and General Chemistry, Egerlandstr. 1, 91058 Erlangen, Germany Tel: +49 9131 85 27464 Email: [email protected] Homepage: https://www.chemistry.nat.fau.eu/munz-group/

Scientific Vita Since 2016 Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Independent Research Group Leader (“Habilitand”). 2014-2016 University of California, San Diego, Postdoctoral Fellow with G. Bertrand. 2013-2014 University of Virginia, Charlottesville, Postdoctoral Fellow with T. B. Gunnoe. 2009-2013 Dresden University of Technology, PhD student with T. Strassner. 2003-2009 ENSC Rennes, Dresden University of Technology, Chemistry Diploma.

Research Field Terminal oxo and imido/nitrene complexes, metal carbenes, stable free carbenes, carbenes as functional groups, bond activation, mechanisms and catalysis, computational chemistry, singlet fission, two-photon absorption

Selected Awards and Recognition 2010 Fellow of the Studienstiftung des Deutschen Volkes 2014 DAAD Fellow, Royal Society of Chemistry 2017 Liebig Fellow of the Fonds der Chemischen Industrie 2019 Max-Buchner Prize of the DECHEMA 2019 Fulbright-Cotrell Award

Representative Publications 1. Grünwald, A.; Orth, N.; Pöthig, A.; Heinemann, F. W.; Munz, D. “An Isolable Palladium Terminal Imido and Catalytic Implications” Angew. Chem. Int. Ed. 2018, 57, 16228. 2. Aghazada, S.; Miehlich, M.; Messelberger, J; Heinemann, F. W.; Munz, D.; Meyer, K. “A Terminal Iron Nitrilimine Complex: Accessing the Terminal Nitride through Diazo N–N Bond Cleavage” Angew. Chem. Int. Ed. 2019, DOI: 10.1002/anie.201910428. 3. Munz, D. “How to Tame a Palladium Terminal Oxo” Chem. Sci. 2018, 9, 1155. 4. Messelberger, J.; Grünwald, A.; Pinter, P.; Hansmann, M. M.; Munz, D. “Carbene Derived Diradicaloids – Building Blocks for Singlet Fission?” Chem. Sci. 2018, 9, 6107. 5. Munz, D. “Pushing Electrons – Which Carbene Ligand for Which Application?” Organometallics 2018, 37, 275.

50 51 Musaev, Djamaladdin (Jamal) G. Director, Cherry L. Emerson Center for Scientific Computation, Emory University Adjunct Professor of Chemistry E-MAIL: [email protected]; ph: 404-450-9584; www.emerson.emory.edu/musaev

Professional Preparation: Institution Major/Area Degree Year Azerbaijan State University, Azerbaijan Quantum Physics BS & MS 1978 USSR Academy of Sciences, Moscow, Russia Quantum Chem Ph.D. 1985 Institute for Molecular Sci., Okazaki, Japan Quantum Chem JSPS fellow 1991-93

APPOINTMENTS: - Director, Cherry L. Emerson Center, Emory University (2006-present); - Adjunct Professor of Chemistry, Emory University (2015-present); - Executive Director, Cherry L. Emerson Center, Emory University, (1993-2006); - JSPS Research Fellow, Institute for Molecular Science, Okazaki, Japan, (1991-1993); - Senior (1986-1993) and Junior (1981-1986) Scientist, Inst. for New Chemical Problems, USSR Acad. of Sci., Chernogolovka, Moscow Region, Russia, (1986-1993); - Junior Scientist, Inst. for Theo. Probls of Chem. Proc., Azerbaijan Acad. of Sci., Baku, (1979-1981)

SELECTED HONORS/DISTINCTIONS • Editorial Board Member, Organometallics, (2015-2018) • Japan Society for Promotion of Science (JSPS) Senior Fellowship, 2013 • Turkish Scientific and Technological Research Council fellow, 2011 • Visiting Professor: Universitat de les Illes Balears, Palme de Mallorca, Spain, (Oct. 2007) • Visiting Professor: The University of Tokyo, Tokyo, Japan (2002) • Japan Society for Promotion of Science (JSPS) Fellowship (1991-1993) RESEARCH INTERESTS: • Nitrogen fixation, alkene/alkyne borylation, olefin polymerization; • Stereoselective C-H bond functionalization (oxidation, amination, alkylation, etc.) • Solar-to-Chemical conversion, Water Oxidation, Alternative energy; • Nano-scale materials with unusual physicochemical properties and reactivity. • Development of Novel Hybrid Computational Methods for interfacial charge transfer in complex syst. REPRESENTATIVE PUBLICATIONS:

1. B. D. McLarney, S. R. Hanna, D. G. Musaev, S. France, “A Predictive Model for the [Rh2(esp)2]- catalyzed Intermolecular C(sp3)–H bond insertion of b-carbonyl ester carbenes: Interplay Theory and Experiment“, ACS Catalysis, 2019, 2. J. T. Fu, Z. Ren, J. Bacsa, D. G. Musaev, H. M. L. Davies, „Desymmetrization of Cyclohexanes by Site-Selective and Stereoselective C–H Functionalization“, Nature, 2018, 564 (7736), 395-397. 3. B. E. Haines, R. Sarpong, D. G. Musaev, „On the Generality and Strength of Transition Metal b-effects“, J. Am. Chem. Soc., 2018, 140, 10612-10618. 4. B. E. Haines, T. Kawakami, K. Murakami, K. Itami, D. G. Musaev, “Key Mechanistic Details and predictive Models for Cu-catalyzed Aromatic C–H Imidation with N-Fluorobenzenesulfonimide.” Chem. Sci., 2017, 8 (2), 988-1002 5. K. Liao, T. Pickle, V. Boyarskikh, J. Bacsa, D. G. Musaev, H. M. L. Davies, „Site-selective and stereoselective functionalization of non-activated tertiary C–H bonds“, Nature, 2017, 551, 609-613.

1

52 Characterization of Reactive Metal Nitrenoids by Crystalline Matrix Isolation

David C. Powers Department of Chemistry, Texas A&M University, College Station, Texas 77845, USA [email protected]

The fleeting lifetimes of reactive intermediates in C–H functionalization chemistry often prevent their direct characterization. For example, the critical nitrenoid intermediates that mediate Rh2- catalyzed C–H amination have eluded characterization for more than 40 years. In the absence of structural characterization of these species, methodological development is often computationally guided. We have been developing new photochemical strategies to generating reactive metal nitrenoids and developing novel crystallographic experiments to enable the direct characterization of these intermediates by X-ray diffraction. This talk will present recent progress towards the structural characterization of a reactive Rh2 nitrenoid, enabled by N2 elimination from an organic azide ligand within a single-crystal matrix. The resulting high-resolution structure displays metrical parameters consistent with a triplet nitrene complex of Rh2. The demonstration of facile access to reactive metal nitrenoids within a crystalline matrix provides a platform for structural characterization of the transient species at the heart of C–H functionalization. We anticipate the availability of structural data will impact the rational development of new catalyst platforms.

References 1. Das, A.; Chen, Y.-S.; Reibenspies, J. H.; Powers, D. C. Characterization of a Reactive Rh2 Nitrenoid by Crystalline Matrix Isolation. J. Am. Chem. Soc. 2019, asap. DOI: 10.1021/jacs.9b09064. 2. Das, A.; Maher, A. G.; Telser, J.; Powers, D. C.* Observation of a Photogenerated Rh2 Nitrenoid Intermediate in C–H Amination. J. Am. Chem. Soc. 2018, 140, 10412–10415. 3. Das, A.; Reibenspies, J. H.; Chen, Y.-S.; Powers, D. C.* Direct Characterization of a Reactive Lattice-Confined Ru2 Nitride by Photocrystallography. J. Am. Chem. Soc. 2017, 139, 2912–2915.

53

CURRICULUM VITAE – David C. Powers

Assistant Professor of Chemistry Department of Chemistry, Texas A&M University, College Station, Texas 77843, USA Tel: 001 (979) 862-3089 Email: [email protected] Homepage: https://www.powerschemistry.com/

Scientific Vita Since 2015 Texas A&M University, Assistant Professor, Department of Chemistry 2012-2015 Harvard University and the Massachusetts Institute of Technology, Post-Doctoral Fellow 2012 Harvard University, Ph.D.

Research Field Aerobic oxidation catalysis, porous materials, synthetic methodology, photochemistry, crystallography, coordination chemistry

Selected Awards and Recognition 2019 Montague-Center for Teaching Excellence Scholar 2019 ACS Organic Division Academic Young Investigator 2019 NSF CAREER Award 2019 Thieme Chemistry Journal Award 2018 DOE Early Career Award 2017 Ralph E. Powe Junior Faculty Enhancement Award 2012 Ruth Kirschstein NIH Postdoctoral Fellowship

Representative Publications 1. Das, A.; Chen, Y.-S.; Reibenspies, J. H.; Powers, D. C.* Characterization of a Reactive Rh2 Nitrenoid by Crystalline Matrix Isolation. J. Am. Chem. Soc. 2019, asap. 2. Hyun, S-M.; Yuan, M.; Maity, A.; Gutierrez, O.*; Powers, D. C.* The Role of Iodanyl Radicals as Critical Chain Carriers in Aerobic Hypervalent Iodine Chemistry. Chem 2019, 5, 2388–2404. 3. Das, A.; Maher, A. G.; Telser, J.; Powers, D. C.* Observation of a Photogenerated Rh2 Nitrenoid Intermediate in C–H Amination. J. Am. Chem. Soc. 2018, 140, 10412–10415. 4. Wang, C.-H.; Das, A.; Gao, W.-Y.; Powers, D. C.* Probing Substrate Diffusion in Interstitial MOF Chemistry with Kinetic Isotope Effects. Angew. Chem. Int. Ed. 2018, 57, 3676–3681. 5. Maity, A.; Hyun, S.-M.; Wortman, A. K.; Powers, D. C.* Oxidation Catalysis by an Aerobically Generated Dess-Martin Periodinane Analogue. Angew. Chem. Int. Ed. 2018, 57, 7205–7209. 6. Maity, A.; Hyun, S.-M.; Powers, D. C.* Oxidase Catalysis via Aerobically Generated Hypervalent Iodine Intermediates. Nat. Chem. 2018, 10, 200–204. 7. Das, A.; Reibenspies, J. H.; Chen, Y.-S.; Powers, D. C.* Direct Characterization of a Reactive Lattice-Confined Ru2 Nitride by Photocrystallography. J. Am. Chem. Soc. 2017, 139, 2912–2915.

54 Taming nitrene reactivity with silver

Jennifer M. Schomaker Department of Chemistry, University of Wisconsin, Madison, Wisconsin 53706, USA [email protected]

One of the primary challenges in catalyst-controlled C-H functionalization is achieving control over the chemo-, site-, and stereoselectivity of the reaction when the precursor contains multiple, competing reactive functional groups. Our group has designed a suite of silver(I) complexes for C=C and C-H functionalizations via metal-catalyzed nitrene transfer (NT) that: 1) enable tuning of the selectivity of the C-N bond-forming event in a broad array of substrates, 2) alter the mechanism of intermolecular NT to influence chemoselectivity, 3) achieve asymmetric aziridination and C-H bond amidations, and 4) accomplish late-stage amination of complex natural products and drug targets. Strategies for new catalyst design, controlling the dynamic behavior of silver complexes, computational studies to understand subtle aspects of mechanism, and directions for 2nd-generation catalysts are presented.

Application of Ag-catalyzed NT to alkenes, dienes, and allenes, followed by carbene transfer, generates unusual aziridinium ylides. Judicious choice of substrate, catalyst, carbene precursor, and reaction conditions enable the ylide to be diverted along different pathways, providing a unified strategy to furnish densely functionalized azetidines, pyrrolidines, piperidines, and N- heterocycles occurring in many natural products and pharmaceuticals. Synthetic and mechanistic aspects of these versatile tandem nitrene/carbene transfer reactions will be discussed.

References 1. Ju, M.; Huang, M., Vine, L. F.; Roberts, J. M.; Dehghany, M.; Schomaker, J. M. "Tunable, catalyst- controlled syntheses of β- and γ-amino motifs enabled by silver complexes." Nature Catalysis 2019, 2, 899-908. 2. Nicastri, K.; Eshon, J.; Schmid, S. C.; Raskop, W.; Guzei, I. A.; Fernández, I.; Schomaker, J. M. "Intermolecular [3+3] Ring-Expansion of Aziridines to Dehydropiperidines through the Intermediacy of Aziridinium Ylides." ChemRvix preprint, 2019, https://doi.org/10.26434/chemrxiv.9961937.v1. 3. Schmid, S. C.; Guzei, I. A.; Fernandez, I.; Schomaker, J. M. "Ring expansion of bicyclic methylene- aziridines via concerted, near-barrierless [2,3]-Stevens rearrangements of aziridinium ylides." ACS Catal. 2018, 8, 7907-7914. 4. Alderson, J. M.; Corbin, J. R.; Schomaker, J. M. "Tunable, chemo- and site-selective nitrene transfer through the rational design of silver(I) catalysts." Accts. Chem. Res. 2017, 50, 2147-2158. 55

CURRICULUM VITAE – Jennifer M. Schomaker

Professor of Chemistry Department of Chemistry, The University of Wisconsin, Madison, WI 53706, USA Tel: 001 (608) 265-2261 Email: [email protected] Homepage: https://schomaker.chem.wisc.edu/

Scientific Vita 2009-present University of Wisconsin-Madison: Assistant Professor (2009), Associate Professor (2015), Professor (2018). 2007-2009 NIH Post-doctoral fellow at University of California, Berkeley with Prof. Robert Bergman and Prof. F. Dean Toste 2002-2006 Ph.D. candidate at Michigan State University with Prof. Babak Borhan

Research Field Asymmetric catalysis, nitrene and carbene chemistry, transformations of allenes, natural products, synthetic methodology

Selected Awards and Recognition 2007 NIH Ruth L. Kirschstein National Research Service Award Research Training Grant 2010 Thieme Chemistry Journal Award 2013 Sloan Research Fellow 2013 NSF-CAREER Award 2013 Michigan State University Distinguished Alumni Lecturer 2013 ACS Division of Organic Chemistry Early Academic Investigator 2014 American Chemical Society WCC Rising Star Award 2015 Michigan State University Recent Alumni Award, College of Natural Science 2016 Kavli Fellow 2018 UW2020 Award: All-Optical Electrophysiology-Electrophysiology (co-PI) 2019 Vilas Faculty Mid-Career Award, UW-Madison 2019 Somojai Miller Visiting Professorship Award, UC-Berkeley

Representative Publications 1. Ju, M.; Huang, M., Vine, L. F.; Roberts, J. M.; Dehghany, M.; Schomaker, J. M. "Tunable, catalyst- controlled syntheses of β- and γ-amino alcohol motifs enabled by silver complexes." Nature Catalysis 2019, 2, 899-908. 2. Nicastri, K.; Eshon, J.; Schmid, S. C.; Raskop, W.**; Guzei, I. A.; Fernández, I.; Schomaker, J. M. "Intermolecular [3+3] Ring-Expansion of Aziridines to Dehydropiperidines through the Intermediacy of Aziridinium Ylides." ChemRvix preprint, 2019, https://doi.org/10.26434/chemrxiv.9961937.v1. 3. Gerstner, N. C.; Schomaker, J. M. "Stereocontrolled Synthesis of the Aminocyclopentitol Core of Jogyamycin via an Ichikawa ." J. Org. Chem. 2019, https://doi.org/10.1021/acs.joc.9b02249. 4. Schmid, S. C.; Guzei, I. A.; Fernandez, I.; Schomaker, J. M. "Ring expansion of bicyclic methylene- aziridines via concerted, near-barrierless [2,3]-Stevens rearrangements of aziridinium ylides." ACS Catal. 2018, 8, 7907-7914. 5. Huang, M.; Yang, T.; Paretsky, J.; Berry, J. F.; Schomaker, J. M. "Inverting Steric Effects: Using 'Attractive' Non-Covalent Interactions to Direct Silver-Catalyzed Nitrene Transfer." J. Am. Chem. Soc. 2017, 139, 17376-17386. 6. Ju, M.; Weatherly, C. D.; Guzei, I. A.; Schomaker, J. M. "Chemo- and enantioselective silver- catalyzed aziridinations." Angew. Chem. Int. Ed. 2017, 56, 9944-9948. 7. Alderson, J. M.; Corbin, J. R.; Schomaker, J. M. "Tunable, chemo- and site-selective nitrene transfer through the rational design of silver(I) catalysts." Accts. Chem. Res. 2017, 50, 2147-2158. 56 Harnessing Carbene Chemistry to Drive Drug Discovery Indrajeet Sharma, Ph.D. Department of Chemistry and Biochemistry, University of Oklahoma, Norman, OK-73019, USA [email protected] Natural products bearing complex structures have served as successful lead molecules in therapeutics development for centuries. More than half of the current drugs available today are either natural products or their derivatives. Despite dramatic Research Program Overview advances in natural products- INSPIRATION inspired drug discovery, many bioactive scaffolds (spirocycles, medium-sized rings, and terpene furanolactones) remain Bioactive Natural Enzymatic Carbene underexploited in probe and drug Cascades Products Scaffolds Cascades discovery owing to the lack of efficient and flexible synthetic CO2R O O Biological Evaluation to H routes. For example, the X identify drug leads O n n stereoselective installation of R R1 O quaternary spiro-centers poses R2 spirocycles medium-sized rings/ challenges in spirocycles synthesis, macrocycles while entropy barrier in ring R1 R2 R1 R2 M = Rh or Fe N ML cyclization limits the synthetic 2 MLn n access to medium sized (8–12 1 ambiphilic O R H atoms) rings. To address these X R2 challenges, the Sharma group is Mechanistic Investigations utilizing diazo-derived metal computational modeling H N CO2R quinolines/ terpeno-furano- O carbenes, which are ambiphilic in pyridines lactones/lactams nature, and offer the possibility of sequential reactions with a and an electrophile, and are ideal for cascade reactions leading to the rapid generation of molecular complexity. Metal carbene derived cascade reactions relies on trapping the ylide intermediate with a suitable electrophile through delayed proton transfer. In this vein, we have identified a synergistic catalyst (Rh/Au) cocktail that initiates a simultaneous diazo-heteroatom insertion/Conia-ene cascade to access tetrahydrofurans, γ- butyrolactones, pyrroles, and spiroheterocycles with complete stereoselectivity. A related cascade transformation undergoes a rhodium-carbene initiated heteroatom insertion/aldol/oxy- Cope sequence to provide functionalized oxacycles and azacycles. The research work has been funded by the NSF CAREER Award, ACS-PRF Doctoral New Investigator Grant, OCAST Health grant and the NIH-NIDA R21/R33 funds. References 1. Hunter, A. C.; Chinthapally, K.; Bain, A.; Steven, J. C.; Sharma, I. "Rh/Au dual catalysis in Carbene sp2-CH Functionalization/Conia-ene Cascade to the Stereoselective Synthesis of Diverse Spirocarbocycles” Adv. Synth. Catal. 2019, 361, 2951–2958. 2. Massaro, N. P.; Stevens, J. C.; Chatterji, A.; Sharma, I. “Stereoselective Synthesis of Diverse Lactones through a Cascade Reaction of Rhodium Carbenoids with Ketoacids” Org. Lett. 2018, 20, 7585–7589. DOI: 10.1021/acs.orglett.8b03327 3. Chinthapally, K.; Massaro, N.; Padgett, H.L.; Sharma, I. “A Serendipitous Cascade of Rhodium Vinylcarbenoids with Aminochalcones for the Synthesis of Functionalized Quinolines” Chem. Comm. 2017, 53, 12205–12208. 57 Indrajeet Sharma, Ph.D. Department of Chemistry and Biochemistry Phone: 405-325-4581; Fax: 405-325-6111 Stephenson Life Science Research Center Email: [email protected] 101 Stephenson Parkway, Norman, OK-73019 Web: http://www.indrajeetsharma.com/ Professional Appointments: 08/2014–present Assistant Professor, Department of Chemistry and Biochemistry, University of Oklahoma, Norman, OK 08/2014–present Full Member, Institute of Natural Products Applications and Research Technologies (INPART), University of Oklahoma, Norman, OK 09/2015-present Associated Faculty, Cellular and Behavioral Neurobiology, University of Oklahoma, Norman, OK Research Field Metal Carbene Chemistry, Diazo Compounds, Synthetic Methodology, Drug Discovery Education and Training 02/2011–07/2014 Lucille Castori Postdoctoral Fellow with Prof. Derek S. Tan, Memorial Sloan–Kettering Cancer Center (MSKCC), New York “Diversity-oriented synthesis of benzannulated spiroketals and Rational design of novel antibiotics” 08/2006–01/2011 Ph.D. in Chemistry with Prof. David Crich at Wayne State University, MI and University of Illinois at Chicago, IL “Chemical synthesis of peptides and peptide thioesters along with mechanistic studies of glycosylation reactions.” 07/2004–06/2006 M.Sc. in Chemistry with Prof. Dipakranjan Mal at IIT Kharagpur, India “[4 + 2] Hauser annulation for the synthesis of anticancer anthracyclines.” 07/2001–06/2004 B.Sc. (Honors) in Chemistry, University of Delhi, India Fellowships and Awards 07/2018–06/2023 NSF-CAREER Award 01/2018–08/2020 ACS-PRF Doctoral New Investigator Award 2016 Junior Faculty Fellowship (JFF) Award, Vice-President for Research 2015 & 2018 Junior Faculty Fellowship (JFF) Award, College of Arts and Sciences 07/2012–06/2014 The Lucilli Castori Postdoctoral Fellowship, MSKCC 03/2010 Travel Award, Division of Organic Chemistry, American Chemical Society 08/ 2010 Selected for ACS, Division of Organic Chemistry sponsored Graduate Research Symposium among top 50 chemistry 4th year PhD students 07/2004–06/2006 Merit Scholarship, IIT-Kharagpur 10/2001 Meritorious Award, University of Delhi OTHER PROFESSIONAL EXPERIENCES Reviewer: NSF and ACS-PRF grants; Organic Letters, The Journal of Organic Chemistry, The European Journal of Organic Chemistry, Chemistry: A European Journal, Bioorganic & Medicinal Chemistry Letters, Carbohydrate Research, Synlett, and Chemical Communications.

58

New Carbon Reactivity Rules

Marcos García Suero Institute of Chemical Research of Catalonia ICIQ, The Barcelona Institute of Science and Technology. Països Catalans 16, 43007 Tarragona, Spain [email protected]

In this lecture, I will show how the catalytic generation of conceptually-novel radical carbenoids, carbyne equivalents, and metal-carbynoids enabled the discovery of new carbon reactivity towards C−H and C−C bonds. The metal or photocatalytic activation of tailored sources revealed new reactivity rules at carbon that have been under-appreciated, not only in the design and discovery of new chemical reactions, but also in their use to build molecular complexity through unexplored disconnection approaches.

59

Dr Marcos García Suero Group Leader at Institute of Chemical Research of Catalonia ICIQ The Barcelona Institute of Science and Technology e-mail: [email protected] Webpage Video Carbynes

Educational/Professional Experience From October 2014 Group Leader at the Institute of Chemical Research of Catalonia - ICIQ. 2010 − 2014 Postdoctoral Researcher. Advisor: Professor Matthew Gaunt, University of Cambridge (UK). Development of new copper-catalyzed reactions and methionine bioconjugation with hypervalent iodine reagents. 2005 (3 months) Internship in the group of Professor Andrew Myers, Harvard University (USA). Total synthesis of novel tetracycline antibiotics. 2003 − 2009 PhD studies. Advisors: Professors José Barluenga, Josefa Flórez, Universidad de Oviedo. Thesis title: Diastereoselective multicomponent cyclizations of Fischer alkoxycarbene complexes, lithium enolates and unsaturated organometallics. (2nd February 2009; Cum Laude). 2002 − 2003 Undergraduate research internship. Advisor: Professor José Gimeno, Universidad de Oviedo. Synthesis of novel cumulenylidene ruthenium complexes with nonlinear optic properties. 1999 − 2003 BSc Chemistry, University of Oviedo.

Research field Catalytic C−H & C−C functionalization strategies for chemical synthesis

Awards & Recognitions 2019 ERC Consolidator Grant (European Commission) 2019 Leonardo Fellowship 2019 (BBVA Foundation) 2019 Young Investigator Award EuChemS/Org Div

2019 Thieme Chemistry Journal Award 2018 JSP Travel Award from the Swiss Chemical Society for the 53rd Bürgenstock Conference 2018 Merck Sigma-Aldrich Young Researcher Award (Royal Spanish Chemical Society RSQE) 2017-2019 SGR Emerging Group Recognition (Generalitat de Catalunya - AGAUR)

Selected Publications • J. Am. Chem. Soc 2019, 141, 15509. Catalytic cleavage of C(sp2)-C(sp2) bonds with Rh-carbynoids. Zhaofeng Wang, Liyin Jiang, Pau Sarró, Marcos G. Suero*. • Chem. Sci. 2019, 10, 9374. A transition-metal-free & diazo-free styrene cyclopropanation. Ana G. Herraiz, Marcos G. Suero*. • Synthesis, 2019, 51, 2821. New Alkene Cyclopropanation Reactions Enabled by Photoredox Catalysis via Radical Carbenoids. Ana G. Herraiz, Marcos G. Suero*. Invited review by Prof. Paul Knochel for the Bürgenstock Conference Special Issue. • Nature, 2018, 554, 86. Generating carbyne equivalents with photoredox catalysis. Zhaofeng Wang, Ana G. Herraiz, Ana M. del Hoyo, Marcos G. Suero*. • Angew. Chem. Int. Ed. 2017, 56, 1610. A Stereoconvergent Cyclopropanation Reaction of Styrenes. Ana M. del Hoyo, Ana G. Herraiz, Marcos G. Suero*. 60 Selective Modification of Carbohydrates by Metal Carbenes

Weiping Tang School of Pharmacy and Department of Chemistry, University of Wisconsin-Madison Madison, WI, USA; E-mail: [email protected]

Carbohydrates are synthetically challenging molecules with vital biological roles in all living systems. Selective synthesis and functionalization of carbohydrates provide tremendous opportunities to improve our understanding on the biological functions of this fundamentally important class of molecules. However, selective functionalization of seemingly identical hydroxyl groups in carbohydrates remains a long-standing challenge in organic synthesis.1 Although tremendous successes have been achieved for selective functionalization of carbohydrate cis-1,2-diols in pyranoses, much less is known about the selective functionalization of the corresponding trans-1,2-diols. While the greater intrinsic reactivity of equatorial OHs in comparison to axial OHs can be significantly amplified by catalysts in cis-1,2-diols, it is not obvious how to systematically differentiate trans-1,2-diols, where both OHs occupy equatorial positions. Recently, we developed a catalytic site-selective acylation method that can systematically differentiate trans-1,2-diols in pyranoses. Selective functionalization of carbohydrate trans-1,2-diols by other types of reactions, such as alkylation, remains largely unexplored. We will describe a practical and predictable method for the site-selective and stereoselective alkylation of carbohydrate hydroxyl groups via Rh(II)-catalyzed insertion of metal carbenoid intermediates.3 This represents one of the mildest alkylation methods for the systematic modification of carbohydrates. Density functional theory (DFT) calculations suggest that the site selectivity is determined in the Rh(II)- carbenoid insertion step, which prefers insertion into hydroxyl groups with an adjacent axial substituent. The subsequent intramolecular enolate protonation determines the unexpected high stereoselectivity. The most prevalent trans-1,2-diols in various pyranoses can be systematically and predictably differentiated based on the model derived from DFT calculations. We also demonstrated that the selective O-alkylation method could significantly improve the efficiency and stereoselectivity of glycosylation reactions. The alkyl groups introduced to carbohydrates by OH insertion reaction can serve as functional groups, protecting groups, and directing groups.

References 1. “Chiral Reagents in Glycosylation and Modification of Carbohydrates.” Wang, H.-Y.; Blaszczyk, S. A.; Xiao, G.; and Tang W. Chem. Soc. Rev. 2018, 47, 681-701. 2. “Catalytic Site-Selective Acylation of Carbohydrates Directed by Cation–n Interaction.” Xiao, G.; Cintron-Rosado, G. A.; Glazier, D. A.; Xi, B.-m.; Liu, C.; Liu, P. and Tang, W. J. Am. Chem. Soc. 2017, 139, 4346-4349. 3. “Site- and Stereoselective O-Alkylation of Glycosides by Rh(II)-Catalyzed Carbenoid Insertion” Wu, J.; Li, X.; Qi, X.; Duan, X.; Cracraft, W. L.; Guizei, I. A.; Liu, P.; and Tang, W. J. Am. Chem. Soc. 2019, ASAP, http://doi.org/10.1021/jacs.9b11262.

61

CURRICULUM VITAE – Weiping Tang

Professor of Pharmaceutical Sciences and Chemistry The Janis Apinis Professor, School of Pharmacy and Department of Chemistry, University of Wisconsin-Madison, Madison, WI, USA Tel: 001 (608) 890-1846 Email: [email protected] Homepage: https://pharmacy.wisc.edu/tang-lab/

Scientific Vita 2019-present Janis Apinis Professor, University of Wisconsin-Madison 2017-present Professor, University of Wisconsin-Madison 2013-2017 Associate Professor, University of Wisconsin-Madison 2007-2013 Assistant Professor, University of Wisconsin-Madison 2005-2007 Postdoctoral Fellow, Harvard University and Broad Institute of Harvard and MIT 2005 Ph. D., Stanford University 1999 M.S., New York University 1997 B.S., Peking University, China

Research Field Synthetic methods, carbohydrate synthesis, medicinal chemistry, and chemical biology

Selected Awards and Recognition 1. Howard Hughes Medical Institute Postdoctoral Fellow (2005-2007) 2. Thieme Synlett/Synthesis Journal Award (2010) 3. Amgen Young Investigator Award (2011) 4. Vilas Mid-Career Investigator Award (2018)

Recent Representative Publications 1. “S‐ Adamantyl Group Directed Site‐ Selective Acylation and Its Applications in the Streamlined Assembly of Oligosaccharides” Blaszczyk. S. A.; Xiao, G.; Wen, P.; Hao, H.; Wu, J.; Wang, B.; Carattino, F.; Li, Z.; Glazier, D. A.; McCarty, B. J.; Liu, P. and Tang, W. Angew. Chem. Int. Ed. 2019, 58, 9542-9546. 2. “Intermolecular Regio- and Stereoselective Hetero-[5+2] Cycloaddition of Oxidopyrylium Ylides and Cyclic Imines” Zhao, C.; Glazier, D. A.; Yang, D.; Yin, D.; Guzei, I. A.; Aristov, M. M.; Liu, P. and Tang, W. Angew. Chem. Int. Ed. 2019, 58, 887-891. 3. “A general strategy for diversifying complex natural products to polycyclic scaffolds with medium-sized rings” Zhao, C.; Ye, Z.; Ma, Z.-X.; Wildman, S. A.; Blaszczyk, S. A.; Hu, L.; Guizei, I. A.; Tang, W. Nat. Commun. 2019, 10, 4015. 4. “Development of Multi-Functional Histone Deacetylase 6 Degraders with Potent Anti-Myeloma Activity” Wu, H.; Yang, K.; Zhang, Z.; Leisten, E. D.; Li, Z.; Xie, H.; Liu, J.; Smith, K. A.; Novakova, Z.; Barinka, C.; and Tang, W. J. Med. Chem. 2019, 62, 7042-7057. 5. “Development of selective small molecule MDM2 degraders based on nutlin” Wang, B.; Wu, S.; Liu, J.; Yang, K.; Xie, H.; and Tang, W.* Eur. J. Med. Chem. 2019, 176, 476-491.

62 Ti-Catalyzed Nitrene Transfer Reactions: Harnessing the TiII/TiIV Redox Couple for New Transformations

Ian A. Tonks Department of Chemistry, University of Minnesota – Twin Cities, Minneapolis, MN USA [email protected]

Titanium is an ideal metal for green and sustainable catalysis—it is the 2nd most earth-abundant transition metal, and the byproducts of Ti reactions (TiO2) are nontoxic. However, a significant challenge of utilizing early transition metals for catalytic redox processes is that they typically do not undergo facile oxidation state changes because of the thermodynamic stability of their high oxidation states. We have recently discovered that Ti imidos (LnTi=NR) can catalyze oxidative nitrene transfer reactions from diazenes via a TiII/TiIV redox couple, and are using this new mode of reactivity to develop a large suite of practical synthetic methods. In this talk, our latest synthetic and mechanistic discoveries related to Ti nitrene transfer catalysis will be discussed, including new synthetic methods for the modular, selective construction of pyrroles via [2+2+1] cycloaddition of alkynes with Ti nitrenes and alkynes, as well as new methods for catalytic oxidative amination of other unsaturated organics by Ti nitrenes.

63

CURRICULUM VITAE – Ian A. Tonks

Associate Professor of Chemistry McKnight Land-Grant Professor Department of Chemistry, University of Minnesota – Twin Cities Minneapolis MN 55401 Tel: 001 (626) 241-3167 Email: [email protected] Homepage: http://tonks.chem.umn.edu

Scientific Vita Since 2013 University of Minnesota – Twin Cities: Assistant Professor (2013), Associate Professor (2019)

Research Field Catalysis, metal nitrene chemistry, reactions of azo compounds, cycloaddition, early transition metal inorganic synthesis, polymerization catalysis

Selected Awards and Recognition 2019 DOE Early Career Award 2019 ACS Organometallics Distinguished Author Award 2018 ACS Organic Division Young Academic Investigator 2018 Grandpierre Lecturer, Columbia University 2018 Thieme Chemistry Journals Award 2017 Sloan Research Fellow, Alfred P. Sloan Foundation 2017 Best Paper Award – Young Investigator Issue, Inorganica Chimica Acta 2016 NIH Maximizing Investigators’ Research Award (R35 MIRA) 2014 ACS Petroleum Research Fund Doctoral New Investigator Award 2007 NSF Graduate Research Fellowship Honorable Mention 2006 Brian Bent Award for Excellence in Teaching, Columbia University 2003 NSF-REU Fellow (2003, 2004, 2005)

Representative Publications 1. Beaumier, E. P.; Pearce, A. J.; See, X. Y.; Tonks, I. A.* Modern Applications of Low Valent Early Transition Metals in Synthesis and Catalysis. Nature Reviews Chemistry 2019, 3, 15. http://dx.doi.org/10.1038/s41570-018-0059-x. 2. Davis-Gilbert, Z. W.; Wen, X.; Goodpaster, J. D.*; Tonks, I. A.* Mechanism of Ti-catalyzed oxidative nitrene transfer in [2+2+1] pyrrole synthesis. J. Am. Chem. Soc. 2018, 140, 7267. http://dx.doi.org/10.1021/jacs.8b03546 3. Chiu, H.-C.; Tonks, I. A.* Trialkylsilyl-protected alkynes as selective cross coupling partners in Ti- catalyzed [2+2+1] pyrrole synthesis. Angew. Chem. Int. Ed. 2018, 57, 6090. http://dx.doi.org/10.1002/anie.201800595 4. Z. W.; Hue, R. J.; Tonks, I. A.* Catalytic Formal [2+2+1] Synthesis of Pyrroles from Alkynes and Diazenes via TiII/TiIV Redox Catalysis. Nature Chemistry 2016, 8, 63. http://dx.doi.org/10.1038/nchem.2386

64

Catalytic Alkyne Functionalization via Metal Carbene Intermediate: Expeditious Access for the Construction of Cyclic Frameworks Qian Yu, Xinfang Xu

Guangdong Provincial Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, China [email protected]

Heterocyclic and carbocyclic compounds are pervasive motifs in various areas of chemistry, medicinal chemistry, and material sciences. Therefore, efforts have been devoted to the construction of cyclic architectures in past decades. The gold-catalyzed alkyne transformation is a practical approach for the effective construction of functionalized cyclic frameworks.1 Especially, the gold-catalyzed alkyne transformations. Inspired by those advances and as the continuation of our interest in alkyne bifunctionalization,2 two distinct methodologies have been formulated with alkyne-tethered diazo compounds: the carbene/alkyne metathesis (CAM) transformation (Path A) and the catalytic diazo-yne carbocyclization (Path B), both delivering the unique vinyl metal carbene intermediate II which is accessible only with limited precursors. Herein, we would like to present the summary of our recent advances in this context, especially the catalytic diazo-yne carbocyclization process, which directly leads to the formation of the key vinyl metal carbene without going through the initial carbene species I in CAM process, and to enable the intermolecular reaction in the terminating step of these cascade reactions.

References 1. (a) Hashmi, A. S. K. ““High Noon” in Gold Catalysis: Carbene versus Carbocation Intermediates” Angew. Chem., Int. Ed. 2008, 47, 6754−6756. (b) Zhang, L. “A Non-Diazo Approach to α-Oxo Gold Carbenes via Gold-Catalyzed Alkyne Oxidation” Acc. Chem. Res. 2014, 47, 877-888. (c) Dorel, R.; Echavarren, A. M. “Gold(I)-Catalyzed Activation of Alkynes for the Construction of Molecular Complexity” Chem. Rev. 2015, 115, 9028-9072. (d) Harris, R. J.; Widenhoefer, R. A. “Gold Carbenes, Gold-Stabilized Carbocations, and Cationic Intermediates Relevant to Gold-Catalysed Enyne Cycloaddition” Chem. Soc. Rev. 2016, 45, 4533−4551. (e) Gorin, D. J.; Toste, F. D. “Relativistic Effects in Homogeneous Gold Catalysis” Nature 2007, 446, 395-403. 2. Pei, C.; Zhang, C.; Qian, Y.; Xu, X. “Catalytic Carbene/Alkyne Metathesis (CAM): A Versatile Strategy for Alkyne Bifunctionalization” Org. Biomol. Chem. 2018, 16, 8677-8685; and the references cited therein.

65

CURRICULUM VITAE – Xinfang Xu

Professor of Chemistry Guangdong Provincial Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China College of Chemistry, Chemical Engineering and Materials Science Soochow University, Suzhou 215123, China Tel: +86-18351037371 Email: [email protected] Scientific Vita Since 2019 Sun Yat-sen University, Professor, School of Pharmaceutical Sciences 2014-2019 Soochow University, Professor, College of Chemistry, Chemical Engineering and Materials Science 2010-2014 University of Maryland at College Park, Postdoctoral Fellow with Prof. Michael P. Doyle, Department of Chemistry and Biochemistry

Research Field Metal Carbene/Nitrene Reaction, Carbene/Alkyne Metathesis (CAM), Cascade Reaction, Alkyne Activation and Bifunctionalization, Asymmetric Catalysis, Heterocycle Synthesis

Representative Recent Publications 1. Pei, C.; Zhang, C.; Qian, Y.; Xu, X. “Catalytic Carbene/Alkyne Metathesis (CAM): A Versatile Strategy for Alkyne Bifunctionalization” Org. Biomol. Chem. 2018, 16, 8677- 8685. 2. Wei, H.; Bao, M.; Dong, K.; Qiu, L.; Wu, B.; Hu, W.; Xu, X. “Enantioselective Oxidative Cyclization/Mannich Addition Enabled by Gold(I)/Chiral Phosphoric Acid Cooperative Catalysis” Angew. Chem. Int. Ed. 2018, 57, 17200-17204. 3. Dong, K.; Pei, C.; Zeng, Q.; Wei, H.; Doyle, M. P.; Xu, X. “Selective C(sp3)-H Bond Insertion in Carbene/Alkyne Metathesis Reactions. Enantioselective Construction of Dihydroindoles” ACS Catal. 2018, 8, 9543-9549. 4. Zheng, Y.; Bao, M.; Yao, R.; Qiu, L.; Xu, X. “Palladium-Catalyzed Carbene/Alkyne Metathesis with Enynone as Carbene Precursor: Synthesis of Fused Polyheterocycles” Chem. Commun. 2018, 54, 350-353. 5. Zhang, C.; Li, H.; Pei, C.; Qiu, L.; Hu, W.; Bao, X.; Xu, X. “Selective Vinylogous Reactivity of Carbene Intermediate in Gold-Catalyzed Alkyne Carbocyclization: Synthesis of Indenols” ACS Catal. 2019, 9, 2440-2447. 6. Hong, K.; Su, H.; Pei, C.; Lv, X.; Hu, W.; Qiu, L.; Xu, X. “Rhodium-Catalyzed Nitrene/Alkyne Metathesis: An Enantioselective Process for the Synthesis of N- Heterocycles” Org. Lett. 2019, 21, 3328-3331. 7. Zeng, Q.; Dong, K.; Pei, C.; Dong, S.; Hu, W.; Qiu, L.; Xu, X. “Divergent Construction of Macrocyclic Alkynes via Catalytic Metal-Carbene C(sp2)-H Insertion and the Buchner Reaction” ACS Catal. 2019, 9, asap, DOI: 10.1021/acscatal.9b04199. 8. Zhang, C.; Hong, K.; Dong, S.; Pei, C.; Zhang, X.; He, C.; Hu, W.; Xu, X. “Gold(I)- Catalyzed Aromatization: Expeditious Synthesis of Polyfunctionalized Naphthalenes” iScience 2019, 9, asap, doi: https://doi.org/10.1016/j.isci.2019.10.042. 66

Advances in Catalytic C(sp3)–N Bond Coupling Reactions: RuII-Catalyzed Asymmetric C–H Amidation of 1,4,2-Dioxazol-5-ones and Photoredox Decarboxylative Coupling of -Diazoacetates with NHPI Esters Wing-Yiu Yu State Key Laboratory of Chemical Biology and Drug Discovery, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University [email protected]

Catalytic C–N bonds formation is one of the major research topics in synthetic chemistry owing to the ubiquity of amino groups in natural products, synthetic intermediates and pharmaceutical agents. Our group aims to develop innovative and practical catalytic cross-coupling reactions with nitrene or carbene precursors for regioselective C–N bond formations. In 2019, we reported the Ru-catalyzed enantioselective annulation of 1,4,2-dioxazol-5-ones to furnish -lactams in up to 97% yield and 98% ee via intramolecular carbonylnitrene C–H insertion. By employing chiral diphenylethylene diamine (dpen) as ligands bearing electron- withdrawing arylsulfonyl substituents, the reactions occur with remarkable chemo- and enantioselectivities; the competing Curtius-type rearrangement was largely suppressed.

We also developed a metal-free photocatalytic coupling reaction for the synthesis of structurally and functionally diverse N-alkyl hydrazones from -diazoacetates and N-alkyl hydroxyphthalimide esters. Employing Rose Bengal as photocatalyst with yellow LEDs irradiation, over 60 N-alkyl hydrazones were synthesized. Fluorescence quenching analysis and deuterium incorporation experiments reveal that Hantzsch ester serves as both electron donor and proton source for the reaction. This strategy offers a simple retrosynthetic disconnection for conventionally inaccessible C(sp3)–rich N-alkyl hydrazones. References 1. Xing, Q.; Chan, C.-M.; Yeung, Y.-W.; Yu, W.-Y., Ruthenium(II)-Catalyzed Enantioselective γ- Lactams Formation by Intramolecular C–H Amidation of 1,4,2-Dioxazol-5-ones. ” J. Am. Chem. Soc 2019, 141, 3849-3853. 2. Chan, C.-M.; Xing, Q.; Chow, Y.-C.; Hung, S.-F.; Yu, W.-Y., Photoredox Decarboxylative C(sp3)– N Coupling of α-Diazoacetates with Alkyl N-Hydroxyphthalimide Esters for Diversified Synthesis of Functionalized N-Alkyl Hydrazones. Org. Lett. 2019, 21, 8037-8043.

67

CURRICULUM VITAE – Wing-Yiu Yu, Michael

Professor & Associate Head of Department State Key Laboratory of Chemical Biology and Drug Discovery, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong Tel: +852 34008725 Email: [email protected] Homepage: http://orcid.org/0000-0003-3181-8908

Scientific Vita Since 2018 Professor, The Hong Kong Polytechnic University 2012-2018 Associate Professor, The Hong Kong Polytechnic University 2005-2012 Assistant Professor, The Hong Kong Polytechnic University 2002-2005 Research Assistant Professor; The University of Hong Kong 1997-2002 Senior Research Assistant / Research Officer, The University of Hong Kong (Supervisor: Prof. Chi-Ming Che) 1993-1997 Croucher Foundation Postdoctoral Fellow, University of Ottawa (Supervisor: Prof. Howard Alper) 1989-1993 Ph.D. in Chemistry, The University of Hong Kong (Supervisor: Prof. Chi-Ming Che)

Research Field C–H Bonds functionalization, reactions of diazo compounds, reactivity of organotransition metal complexes with carboradicals, carbenes and nitrenes

Selected Awards and Recognition 1993-96 Croucher Foundation Postdoctoral Fellowship 2011 Best teaching award in ABCT 2014 ABCT Star Award, PolyU 2014 Asian Core Program Lectureship Award (ICCEOCA-8, Japan) 2015 Asian Core Program Lectureship Award (ICCEOCA-9, Taiwan) 2015 Asian Core Program Lectureship Award (ICCEOCA-9, China) 2016 ABCT Star Award, PolyU

Representative Publications 1. Xing, Q.; Chan, C.-M.; Yeung, Y.-W.; Yu, W.-Y., Ruthenium(II)-Catalyzed Enantioselective γ- Lactams Formation by Intramolecular C–H Amidation of 1,4,2-Dioxazol-5-ones. ” J. Am. Chem. Soc 2019, 141, 3849-3853. 2. Chan, C.-M.; Xing, Q.; Chow, Y.-C.; Hung, S.-F.; Yu, W.-Y., Photoredox Decarboxylative C(sp3)– N Coupling of α-Diazoacetates with Alkyl N-Hydroxyphthalimide Esters for Diversified Synthesis of Functionalized N-Alkyl Hydrazones. Org. Lett. 2019, 21, 8037-8043. 3. Ng, F.-N.; Chan, C.-M.; Li, J.; Sun, M.; Lu, Y.-S.; Zhou, Z.; Huang, B.; Yu, W.-Y., [RhIII(Cp*)]- catalyzed arylfluorination of α-diazoketoesters for facile synthesis of α-aryl-α-fluoroketoesters. Org. Biomol. Chem. 2019, 17, 1191-1201 4. Ng, F.-N.; Lau, Y.-F.; Zhou, Z.; Yu, W.-Y., [RhIII(Cp*)]-Catalyzed Cascade Arylation and Chlorination of α-Diazocarbonyl Compounds with Arylboronic Acids and N-Chlorosuccinimide for Facile Synthesis of α-Aryl-α-chloro Carbonyl Compounds. Org. Lett. 2015, 17, 1676-1679. 5. Chan, W.-W.; Lo, S.-F.; Zhou, Z.; Yu, W.-Y., Rh-Catalyzed Intermolecular Carbenoid Functionalization of Aromatic C–H Bonds by α-Diazomalonates. J. Am. Chem. Soc. 2012, 134, 13565-13568.

68 Mechanisms of Biocatalytic Heme Carbene Transfer Reactions

Yong Zhang Department of Chemistry and Chemical Biology, Stevens Institute of Technology, Hoboken, NJ 07030, USA [email protected]

Engineered heme proteins and biomimetic iron porphyrins have recently been found to possess excellent catalytic properties for numerous carbene transfer reactions, such as C-H insertion, cyclopropanation, and Si-H insertion. We have performed systematic DFT calculations of these three heme carbene transfer reactions regarding different substrates, carbenes, porphyrins, and axial ligands to provide some first mechanistic information. In contrast with the native heme enzymatic reactions which typically employ ferryl intermediate and radical mechanism, these non-native reactions possess an FeII-based concerted carbene transfer mechanism. Results are consistent with experimental data of radical trapping, kinetic isotope effects, and structure-reactivity data. Detailed geometric and electronic profiles along these heme carbene transfer pathways were revealed to help understand the origin of experimental reactivity trends due to modifications on substrates, carbenes, and catalysts. Quantitative relationships between reaction barriers and some electronic and geometric properties were found.

In addition, the first quantitative predictions of protein environment effect on stereoselectivity were reported, which are within 1% errors compared to experimental de and ee data. High stereocontrol is achieved through two major mechanisms: by enforcing a specific conformation of the heme-bound carbene within the active site and by controlling the geometry of attack of the olefin on the carbene via steric occlusion and attractive van der Waals forces and protein-mediated π−πinteractions with the olefin substrate. The protein environment effect was also found to be important in reproducing the different experimental chemoselectivity of cyclopropanation vs. C-H functionalization in indole and benzofuran reactions. Such work furnishes some significant mechanistic results for both understanding the reactivity of current systems and guiding the future development of biological catalysts for this class of synthetically important, abiotic transformations.

References1. Khade, R. L.; Zhang, Y. “C-H Insertions by Iron Porphyrin Carbene: Basic Mechanism and Origin of Substrate Selectivity” Chem. Eur. J., 2017, 23, 17654-17658. 2. Tinoco, A.; Wei, Y.; Bacik, J. P.; Moore, E. J.; Ando, N.; Zhang, Y.; Fasan, R. “Origin of high stereocontrol in olefin cyclopropanation catalyzed by an engineered carbene transferase” ACS Catal. 2019, 9, 1514-1524. 3. Khade, R. L.; Chandgude, A. L.; Fasan, R.; Zhang, Y. “Mechanistic Investigation of Biocatalytic Heme Carbenoid Si-H Insertions” ChemCatChem 2019, 11, 3101-3108. 4. Vargas, D.; Khade, R. L.; Zhang, Y.; Fasan, R. “Biocatalytic strategy for highly diastereo- and enantioselective synthesis of 2,3-dihydrobenzofuran based tricyclic scaffolds” Angew. Chem. Int. Ed. 2019, 58, 10148-10152.

69 CURRICULUM VITAE – Yong Zhang

Professor of Chemistry Department of Chemistry and Chemical Biology, Stevens Institute of Technology, Hoboken, New Jersey 07030, USA Tel: 001 (201) 216-5513 Email: [email protected] Homepage: https://web.stevens.edu/facultyprofile/?id=1572

Scientific Vita Since 2010 Associate Professor (2010-2019), Professor (since 2019), Department of Chemistry and Chemical Biology, Stevens Institute of Technology 2007-2010 Assistant Professor, Department of Chemistry and Biochemistry, University of Southern Mississippi 2000-2007 Postdoctoral Research Associate (2000-2005), Research Scientist (2005-2007), Department of Chemistry, University of Illinois at Urbana-Champaign 1999-2000 Associate Professor, Department of Chemistry, Nanjing University, China

Research Field Computational Chemistry, Biophysical Chemistry, Bioinorganic Chemistry, Catalysis and Biocatalysis

Selected Awards and Recognition 2018,2017 Recognition of Outstanding Teaching Evaluation, Office of the Vice Provost for Academics, Stevens Institute of Technology 2015,2013 Certificate of Recognition as an ACS Chemistry Ambassador, American Chemical Society Committee on Public Relations and Communications 2009 Aubrey Keith Lucas and Ella Ginn Lucas Endowment for Faculty Excellence Awards, University of Southern Mississippi 2004 National Second-class Award of Natural Sciences, China 2002 National First-class Award for the Advancement of Science and Technology, Ministry of Education, China 2000 National Award for University Key Teachers, Ministry of Education, China 1999 Star-of-Hope Research and Teaching Award for the Young Faculty, Nanjing University, China 1997 Chinese Post-doctoral Science Foundation Fellow, China

Representative Publications 1. Wei, Y.; Tinoco, A.; Steck, V.; Fasan, R.; Zhang, Y. “Cyclopropanations via Heme Carbenes: Basic Mechanism and Effects of Carbene Substituent, Protein Axial Ligand, and Porphyrin Substitution” J. Am. Chem. Soc. 2018, 140, 1649-1662. 2. Bhagi-Damodaran, A.; Michael, M. A.; Zhu, Q. H.; Reed, J.; Sandoval, B. A.; Moënne-Loccoz, P.; Zhang, Y.; Lu, Y. “Why is copper preferred over iron for oxygen activation and reduction in haem- copper-oxidases”. Nat. Chem. 2017, 9, 257-263. 3. Khade, R. L.; Yang, Y.; Shi, Y.; Zhang, Y. “HNO Binding in Heme Proteins: Effects of Iron Oxidation State, Axial Ligand, and Protein Environment” Angew. Chem. Int. Ed. 2016, 55, 15058- 15061. 4. Khade, R. L.; Zhang, Y. “Catalytic and Biocatalytic Iron Porphyrin Carbene Formation: Effects of Binding Mode, Carbene Substituent, Porphyrin Substituent, and Protein Axial Ligand” J. Am. Chem. Soc. 2015, 137, 7560-7563. 5. Khade, R. L.; Fan, W.; Ling, Y.; Yang, L.; Oldfield, E.; Zhang, Y. “Iron Porphyrin Carbenes as Catalytic Intermediates: Structures, Mossbauer and NMR Spectroscopic Properties, and Bonding” Angew. Chem. Int. Ed., 2014, 53, 7574-7578.

70

Vinyl Cations as Reactive Intermediates for C-H Insertion

Matthias Brewer Department of Chemistry, University of Vermont, Burlington, Vermont 05405, USA [email protected]

Interest in vinyl cations as synthetic intermediates has reemerged over the past few years with the advent of mild and selective ways to form these reactive species. Importantly, vinyl cations can display carbene- like reactivity, and we have taken advantage of this to effect C-H insertion reactions that give cyclopentenone products which can’t be formed by C-H insertion of metal carbenes.1 This reaction takes advantage of β-hydroxy-α-diazo carbonyl compounds as vinyl cation precursors. As shown below, Lewis acids facilitate the loss of the β-hydroxy group which gives vinyl diazonium 2. This species spontaneously loses molecular nitrogen to yield exocyclic vinyl cation 3. If an electron releasing group is present in the γ-position (e.g. 3, Y = OTBS), a Grob-like fragmentation ensues which leads to an aldehyde tethered ynone (4).2 Compounds that lack an electron releasing group do not fragment, but instead undergo a 1,2- shift across the alkene to give a second vinyl cation (5). Vinyl cation 5 can then participate in an intramolecular C-H insertion reaction to give the cyclopentenone product 6. On the other hand, if an aromatic ring is present, then an electrophilic aromatic substitution reaction (formally a C-H insertion on the aryl ring) can occur to give indenone 7.3

In order for these vinyl cation reaction sequences to be useful strategies for synthesis, the migratory aptitude of different groups in the 1,2-shift in systems that are not symmetric (e.g. 3 → 5, Y = alkyl, aryl) must be predictable. In this poster presentation we report experimental and computational studies that detail the migratory aptitude of different groups in the 1,2-shift event. In addition, we have been exploring the use of the vinyl cation intermediates in intramolecular reactions other than C-H insertion, and will provide preliminary results on reactions that involve pendent alkenes.

References 1) Cleary, S.; Hensinger, M.; Brewer, M. “Remote C-H Insertion of Vinyl Cations Leading to Cyclopentenones” Chem. Sci., 2017, 8, 6810-6814.

2) Draghici, C.; Brewer, M., “Lewis acid promoted carbon-carbon bond cleavage of γ-silyloxy- β-hydroxy-α-diazoesters” J. Am. Chem. Soc. 2008, 130(12), 3766-3767.

3) Fang, J.; Brewer, M. “Intramolecular Vinylation of Aryl Rings by Vinyl Cations” Org. Lett. 2018, 20, 7384-7387.

71

CURRICULUM VITAE – Matthias Brewer

Professor of Chemistry Department of Chemistry, University of Vermont, Burlington, Vermont 05405, USA Tel: 001 (802) 656-1042 Email: [email protected] Homepage: http://www.uvm.edu/~mbrewer1/

Scientific Vita Since 2005 University of Vermont, Department of Chemistry: Assistant Professor (2005), Associate Professor (2011), Professor (2016) 2002-2005 University of California –Irvine: Postdoctoral Fellow with Prof. Larry Overman

Research Field Organic synthesis methods; reactions of diazo compounds; C-H insertions; vinyl cations; heteroallenes; nitrenium ions; natural product synthesis; synthesis of small molecule therapeutics

Selected Awards and Recognition 2002 NIH National Research Service Award Postdoctoral Research Fellowship 2006 Amgen New Faculty Award 2008 NSF CAREER Award

Representative Publications 1. Cleary, S.E.; Li, X.; Yang, L.-C.; Houk, K.N.; Hong, X.; Brewer, M. “Reactivity Profiles of Diazo Amides, Esters and Ketones in Transition Metal Free C-H Insertion Reactions” J. Am. Chem. Soc. 2019, 141, 3558-3565. 2. Fang, J.; Brewer, M. “Intramolecular Vinylation of Aryl Rings by Vinyl Cations” Org. Lett. 2018, 20, 7384-7387. 3. Cleary, S.; Hensinger, M.; Brewer, M. “Remote C-H Insertion of Vinyl Cations Leading to Cyclopentenones” Chem. Sci., 2017, 8, 6810-6814. 4. Al-Bataineh, N.; Houk, K.N.; Brewer, M.; Hong, X. “(2+1)-Cycloaddition Reactions Give Further Evidence of the Nitrenium-like Character of 1-Aza-2-azoniaallene Salts” J. Org. Chem. 2017, 82(7), 4001-4005.

72 Efficient Copper Catalyzed Multicomponent Synthesis of N-acyl amidines via Acyl Nitrenes

Kaj van Vliet, Lara Polak, Maxime Siegler, Jarl Ivar van der Vlugt, Célia Fonseca Guerra and Bas de Bruin*

van ’t Hoff Institute for Molecular Sciences (HIMS), Universiteit van Amsterdam (UvA), [email protected]

Direct synthetic routes to amidines are desired, as they are widely present in many biologically active compounds and organometallic complexes.1 N-Acyl amidines in particular can be used as a starting material for the synthesis of heterocycles and have several other applications. Here, we describe a fast and practical copper catalyzed 3-component reaction of aryl acetylenes, amines and easily accessible 1,4,2-dioxazol-5-ones to N-acyl amidines, generating CO2 as the only by-product.2 Transformation of the dioxazolones on the Cu-catalyst generates acyl nitrenes that rapidly insert into the copper acetylide Cu−C bond rather than undergoing an undesired . For non-aromatic dioxazolones, [Cu(OAc)(Xantphos)] is a superior catalyst for this transformation, leading to full substrate conversion within 10 minutes. For the direct synthesis of N-benzoyl amidine derivatives from aromatic dioxazolones, [Cu(OAc)(Xantphos)] proved to be inactive, but moderate to good yields were obtained when using simple CuI as the catalyst. Mechanistic studies revealed the aerobic instability of one of the intermediates at low catalyst loadings, but the reaction could still be performed in air for most substrates when using catalyst loadings of 5 mol%. The herein reported procedure does not only provide a new, practical and direct route to N-acyl amidines, but also represents a new type of C−N bond formation.

References: 1. Greenhill, J. V.; Lue, P. Amidines and Guanidines in Medicinal Chemistry. Prog. Med. Chem. 1993, 30, 203–326. 2. Efficient Copper Catalyzed Multi-component Synthesis of N-acyl am-idines via Acyl Nitrenes van Vliet, K.; Polak, L.; Siegler, M.; van der Vlugt, J.I.; Fonseca Guerra, C.; de Bruin, B. J. Am. Chem. Soc. 2019, 141, 15240-15249.

73

CURRICULUM VITAE – Bas de Bruin

Professor of Chemistry Van ‘t Hoff Insitute for Molecular Chemistry University of Amsterdam Science Park 904 Amsterdam Tel: +31 20 525 6495 Email: [email protected]

Homepage: http://www.homkat.nl/People/ScientificStaff/BasdeBruin/BasdeBruin.htm

Bas de Bruin studied chemistry at the University of Nijmegen from 1989-1994. He obtained his PhD (April 20, 1999) from the same university (Rh Mediated Olefin Oxygenation). He did his postdoc in the group of Wieghardt at the Max-Planck Institut für Bioanorganische Chemie (Mülheim a/d Ruhr, Germany, April 1999-April 2000). After his postdoc he returned to the University of Nijmegen as an assistant professor in Inorganic Chemistry (Metal-Organic Chemistry), where he was involved in several research activities ranging from olefin oxygenation, radical organometallic chemistry, C1 (carbene) polymerisation, EPR spectroscopy, catalysis, DFT calculations and (catalytic) organic synthesis of new materials. November 2005 he moved to the University of Amsterdam (UvA, group Reek, Homogeneous and Supramolecular Catalysis), where he was promoted to Associate Professor (UHD, October 2008). January 2013 he was promoted to Full Professor (chair) at the same university.

Selected Awards and Recognition 1. Alexander von Humboldt postdoc fellowship (1999). 2. NWO VIDI Award grant (2005). 3. ERC Starting/Consolidator Award Grant (2008). 4. NWO VICI Award Grant (2012). 5. Advance Research Center Chemical Building Blocks Consortium (ARC-CBBC) Member (2016).

Representative Publications 5. Efficient Copper Catalyzed Multi-component Synthesis of N-acyl am-idines via Acyl Nitrenes van Vliet, K.; Polak, L.; Siegler, M.; van der Vlugt, J.I.; Fonseca Guerra, C.; de Bruin, B. J. Am. Chem. Soc. 2019, 141, 15240-15249. [link]

4. Catalytic dibenzocyclooctene synthesis via cobalt(III)-carbene radical and ortho-quinodimethane intermediates te Grotenhuis, C.; van den Heuvel, N.; van der Vlugt, J. I.; de Bruin, B. Angew. Chem. Int. Ed., 2018, 57, 140. [link]

3. Catalytic 1,2-Dihydronaphthalene and E-Aryl-Diene Synthesis via CoIII-Carbene Radical and o-Quinodimethane Intermediates te Grotenhuis, C.; Das, B.G.; Kuijpers, P.F. Hageman, W.; Trouwborst, M.; de Bruin, B. Chem. Sci., 2017, 8, 8221. [link]

2. Hydrogenation of Carboxylic Acids with a Homogeneous Cobalt Catalyst - Korstanje, T.J.; van der Vlugt, J.I.; Elsevier, C.J.; de Bruin, B., Science, 2015, 350 (6258), 298. DOI: 10.1126/science.aaa8938. [link]

1. Characterization of Porphyrin-Co(III)-‘Nitrene radical’ species relevant in catalytic nitrene transfer reactions - Goswami, M.; Lyaskovskyy, V.; Domingos, S.R.; Buma, W.J.; Woutersen, S.; Troeppner, O.; Ivanović-Burmazović, I.; Lu, H.; Cui, X.; Zhang, X.P.; Reijerse, E.J.; DeBeer, S.; van Schooneveld, M.M.; Pfaff, F. F.; Ray, K.; de Bruin, B., J. Am. Chem. Soc., 2015, 137, 5468. [link]

74 Catalytic Asymmetric Transformations from Keto-Sulfoxonium Ylides and Diazo Compounds

Antonio C. B. Burtoloso Department of Physical-Chemistry, Chemistry Institute at São Carlos, University of São Paulo, São Carlos, SP, 13560-970, Brazil [email protected]

Sulfur ylides and diazo carbonyl compounds are important molecules that can perform several transformations.1-3 Although diazo compounds have proven to be interesting building blocks for catalytic asymmetric reactions (for example in N-H, O-H, C-H insertions and cyclopropanations), there is still many possible asymmetric transformations not yet evaluated from these compounds. A worse scenario is the catalytic asymmetric reaction from sulfur ylides, especially the ones involving carbene intermediates. Herein, we would like to show some new catalytic and asymmetric transformations from both diazo compounds (Friedel-Crafts alkylation) and sulfur ylides (S-H and N-H insertions) in the presence of metals, organocatalysts or a combination of both.

References 1. R. Oost, R. J. D. Neuhaus, J. Merad and N. Maulide, Sulfur Ylides in Organic Synthesis and Transition Metal Catalysis, in Structure and Bonding, Springer, Berlin, Heidelberg, 2017. 2. M. P. Doyle, M. A. McKervey and T. Ye, Modern Catalytic Methods for Organic Synthesis with Diazo Compounds, John Wiley & Sons, New York, NY, 1998. 3. A. Ford, H. Miel, A. Ring, C. N. Slattery, A. R. Maguire and M. A. McKervey, Chem. Rev., 2015, 115, 9981.

75

Combining Metal Catalysis and Organocatalysis for the Asymmetric N-H Insertion Reaction with Sulfoxonium Ylides

Lucas G. Furniel and Antonio C. B. Burtoloso* São Carlos Institute of Chemistry, University of São Paulo, São Carlos, Brazil [email protected]; [email protected]

Metal catalysed asymmetric N-H insertion is a straightforward method to construct enantioenriched α-aminofunctionalized carbonyl compounds, which are motifs of importance in synthetic organic chemistry and biology.1 The use of α-diazocarbonyl as substrates in these reactions is well stabilished.2–8 However there are no reports of such transformations using sulfoxonium ylides (Scheme 1), which are safer and more stable synthetic equivalents of diazocarbonyl compounds. Scheme 1. Comparison between diazo compounds and sulfoxonium ylides in enantioselective N-H insertion.

Herein we report the first enantioselective transformation with sulfoxonium ylides via metal carbene chemistry. Using a combination between metal catalysis and organocatalysis, α- aminoesters were obtained as N-H insertion products in yields up to 83% and enantiomeric excesses up to 80% (Scheme 2). Studies aiming expansion of the substrate scope are now underway. Scheme 2. Enantioselective N-H insertion with Sulfoxonium Ylides.

. References (1) Nájera, C.; Sansano, J. M. Chem. Rev. 2007, 107 (11), 4584–4671. (2) Lee, E. C.; Fu, G. C. J. Am. Chem. Soc. 2007, 129 (40), 12066–12067. (3) Liu, B.; Zhu, S.-F.; Zhang, W.; Chen, C.; Zhou, Q.-L. J. Am. Chem. Soc. 2007, 129 (18), 5834–5835. (4) Hou, Z.; Wang, J.; He, P.; Wang, J.; Qin, B.; Liu, X.; Lin, L.; Feng, X. Angew. Chem. Int. Ed. 2010, 49 (28), 4763–4766. (5) Saito, H.; Uchiyama, T.; Miyake, M.; Anada, M.; Hashimoto, S.; Takabatake, T.; Miyairi, S. Heterocycles 2010, 81 (5), 1149. (6) Zhu, S.-F.; Zhou, Q.-L. Acc. Chem. Res. 2012, 45 (8), 1365–1377. (7) Xu, B.; Zhu, S.-F.; Zuo, X.-D.; Zhang, Z.-C.; Zhou, Q.-L. Angew. Chem. Int. Ed. 2014, 53, 3913–3916. (8) Ren, Y.-Y.; Zhu, S.-F.; Zhou, Q.-L. Org. Biomol. Chem. 2018, 16 (17), 3087–3094.

Acknowledgements Grants 2018/17800-3, 2017/23329-9, 2013/18009-4, São Paulo Research Foundation (FAPESP) and 140276/2018-1, National Council for Scientific and Technological Development (CNPq).

76 Azavinyl carbenes from imidoyl-substituted sulfoxonium ylides: Application in the synthesis of indoles

Clarice Alves Dale Caiuby, Antonio Carlos Bender Burtoloso* Department of Physical Chemistry, Chemistry Institute of São Carlos, USP, CEP 13563-120 [email protected]; [email protected]

Azavinyl carbenes have been established as promising building blocks in organic synthesis. This class of metal-carbene species can only be accessed in situ from diazo imine compounds by means of the ring-chain tautomerization of 1-N-sulfonyl-1,2,3-triazoles. Once formed, these diazo imine compounds can be intercepted by rhodium complexes to produce highly reactive azavinyl metal-carbenes species, which can act as versatile intermediates for N-heterocycles synthesis.1 Since sulfur ylides are considered synthetic equivalents of diazo compounds to generate metal carbenes,2 we visualized the possibility of employing N-aryl-imidoyl sulfoxonium ylides to furnish azavinyl carbenes as an alternative to the use of N-sulfonyl triazoles (diazo precursor). The synthesis of this class of sulfur ylides was first reported in 1977 by Gilchrist and co-workers.3 Based on this methodology we have prepare 22 new examples of substituted N-aryl-imidoyl sulfoxonium ylides from the corresponding imidoyl chloride substrates. These imidoyl sulfoxonium ylides were applied in intramolecular C-H functionalization reactions, catalyzed by an iridium complex, to provide substituted indoles in just one step.

Acknowledgments: We acknowledge FAPESP (2017/23837-4), CNPq and CAPES for financial support. References: 1 (a) Hockey, S. C.; Henderson, L. C. Aust. J. Chem. 68, 1796, 2015. (b) Chuprakov, S.; Kwok, S. W.; Fokin, V. V. Aust. J. Chem. 2015, 68, 1796–1800. (c) Hoorneff, T.; Chuprakov, S.; Chernyak, N.; Gevorgyan, V.; Fokin, V. V. J. Am. Chem. Soc. 2008, 130, 14972–14974. (d) Grimster, N.; Zhang, L.; Fokin, V.V. J. Am. Chem. Soc. 2010, 132, 2510–2511. (e) Selander, N.; Worrell, B. T.; Chuprakov, S.; Velaparthi, S.; Fokin, V. V. J. Am. Chem. Soc. 2012, 134, 14670–14673. (f) Chuprakov, S; Malik, J. A.; Zibinsky, M.; Fokin, V. V. J. Am. Chem. Soc. 2011, 133, 10352-10355. 2 (a) Burtoloso, A. C. B.; Dias, R. M. P.; Leonarczyk, I.A. Eur. J. Org. Chem. 2013, 5005-5016. (b) Wu, X.; Sun, S.; Yu, J-T.; Cheng, J. Synlett, 2018, 29, A-I. (b) Vaitla, J.; Bayer, A. Synthesis, 2018, 50, A - Q. (c) Hu, F.; Xia, Y.; Ma, C.; Zhanga Y.; Wang, J. Chem. Commun., 2015, 51, 7986-7995. 3(a) Faragher, R.; Gilchrist, T. L. J. Chem. Soc., Perkin Trans. 1,0, 1196, 1977. (b) Faragher, R.; Gilchrist, T.L.; Southon, I. W. J. Chem. Soc., Perkin Trans. 1, 0, 2352, 1981.

77

CURRICULUM VITAE – Antonio C. B. Burtoloso

Associate Professor Department of Physical Chemistry, Chemistry Institute at São Carlos, University of São Paulo, São Carlos, SP, 13563-120, Brazil

Tel: +55 16 3373 8641 Email: [email protected] Homepage: https://burtolosogroup.wixsite.com/iqsc-usp

Scientific Vita Since 2015 University of São Paulo, Associate Professor, Chemistry Institute at São Carlos. 2008-2015 University of São Paulo, Assistant Professor, Chemistry Institute at São Carlos. 2006-2007 The Scripps Research Institute, San Diego, Postdoctoral Fellow. 2002-2006 State University of Campinas (UNICAMP), PhD student. 2001-2002 Federal University of Rio de Janeiro (UFRJ), master student. 1996-2001 Federal University of Rio de Janeiro (UFRJ), undergraduate student.

Research Field New transformations and asymmetric catalysis from sulfur ylides and diazo compounds, synthetic methodology, biomass and sustainable chemistry.

Selected Awards and Recognition 2008 São Paulo Research Foundation (FAPESP) Young Investigator Grant. 2012 Affiliated Member of the Brazilian Academy of Science. 2013 Royal Society of Chemistry/Brazilian meeting on Organic Synthesis Young Investigator Award.

Representative Publications 1. Ahmad, Anees; Burtoloso, Antonio C. B. Total Synthesis of (±)-Brussonol and (±)- Komaroviquinone via a Regioselective Cross-Electrophile Coupling of Aryl Bromides and Epoxides. Organic Letters, 2019, 21, 6079-6083. 2. Gallo, Rafael Douglas Clemente; Burtoloso, Antonio C. B. Silica-supported HClO4 promotes catalytic solvent- and metal-free O-H insertion reactions with diazo compounds. Green Chemistry, 2018, 20, 4547-4556. 3. Talero, Alexánder Garay; Martins, Bruna Simões; Burtoloso, Antonio C. B. Coupling of Sulfoxonium Ylides with Arynes: A Direct Synthesis of Pro-Chiral Aryl Ketosulfoxonium Ylides and Its Application in the Preparation of α-Aryl Ketones. Organic Letters, 2018, 20, 7206-7211. 4. Gallo, Rafael; Ahmad, Anees; Metzker, Gustavo; Burtoloso, A. C. B. α,α-Alkylation-Halogenation and Dihalogenation of Sulfoxonium Ylides. A Direct Preparation of Geminal Difunctionalized Ketones. Chemistry-A European Journal, 2017, 23, 16980-16984. 5. Dias, Rafael M. P.; Burtoloso, A. C. B. Catalyst-Free Insertion of Sulfoxonium Ylides into Aryl Thiols. A Direct Preparation of β-Keto Thioethers. Organic Letters. 2016, 18, 3034-3037. 6. Bernardim, Barbara; Cal, Pedro M.S.D.; Matos, Maria J.; Oliveira, Bruno L.; Martínez-Sáez, Nuria; Albuquerque, Inês S.; Perkins, Elizabeth; Corzana, Francisco; Burtoloso, Antonio C.B.; Jiménez- Osés, Gonzalo; Bernardes, Gonçalo J. L. Stoichiometric and irreversible cysteine-selective protein modification using carbonylacrylic reagents. Nature Communications., 2016, 7, 13128. 7. Burtoloso, Antonio C. B., Dias, Rafael M. P., Bernardim, Barbara α,β-Unsaturated Diazoketones as Useful Platforms in the Synthesis of Nitrogen Heterocycles. Accounts of Chemical Research, 2015, 48, 921-934.

78 Continuous flow assisted rhodium catalyzed carbene insertion reactions

Long Hay AUa, Chi Ming CHEa,b* aState Key Laboratory of Synthetic Chemistry and Department of Chemistry, University of Hong Kong, Pokfulam Road, Hong Kong, China bHKU Shenzhen Institution of Research and Innovation, Shenzhen, China [email protected]

In this century, diazo compounds are used for a vast amount of reactions1. From direct alkylation of hydrocarbon feedstocks2 to [3+3]-cycloadditons3, we have witnessed the evolution of an important class of reagent. However, the preparation of reactive diazo compounds is often challenging as such neutral organic compounds are sensitive to shock and heat. In addition, the alkylating property of diazo compounds could alkylate DNA (demonstrating its toxicity4). Recently, emerging continuous-flow techniques were applied in generation of reactive diazo compounds5. This new technology allows us to prepare the immature class of reactive diazo compounds from respective hydrazones with high atom economy (hydrogen and nitrogen as the sole side products) in a scalable fashion. With the presence of rhodium porphyrin catalysts and the target substrates, C-H and C=C bond carbene inserted products could be obtained with yield up to 90% and 95% respectively. Compared to semi-batch conditions, fully continuous-flow set- ups minimize the reaction time by 29 times (24 minutes).

References

1. Ford, A.; Miel, H.; Ring, A.; Salttery, C. N.; Maguire, A. R.; McKervy, M. A. “Modern Organic synthesis with -Diazocarbonyl Compounds” Chem. Rev. 2015, 115, 9981-10080. 2. Davies, H. M. L.; Liao, K. “Dirhodium tetracarboxylates as catalysts for selective intermolecular C-H functionalization” Nature Reviews Chemistry 2019, 3, 347-360. 3. Xu, X.; Doyle, M. P. “The [3+3]-Cycloaddition Alternative for Heterocycle Syntheses: Catalytically Generated Metalloenolcarbenes as Dipolar Adducts” Acc. Chem. Res. 2014, 47, 1396-1405. 4. Hartley, J. A.; O’Hare, C. C.; Baumgart, J. “DNA alkylation and interstrand crosslinking by treosulfan ” British Journal of Cancer. 1999, 79, 264-266. 5. Tran, D. N.; Battilocchio, C.; Lou, S-B; Hawkins, J. M.; Ley, S. V. “Flow chemistry as a discovery tool to acess sp2-sp3 cross-coupling reactions via diazo compounds” Chem. Sci. 2015, 6, 1120-1125.

79 N-Heterocyclic Carbene Iron(III) Porphyrin-Catalyzed Intramolecular C(sp3)–H Amination of Alkyl Azides under Thermal and Microwave-assisted Conditions

Ka-Pan Shing,a Yungen Liu,b Bei Cao,a Xiao-Yong Chang,a Tingjie Youb and Chi-Ming Chea,b,* a State Key Laboratory of Synthetic Chemistry and Department of Chemistry, The University of Hong Kong, Hong Kong, China. b HKU Shenzhen Institute of Research and Innovation, Shenzhen, China. [email protected]

Abstract

Many bio-active alkaloids are structurally complicated, and their syntheses rely heavily on the pre-functionalizations prior to functional group interconversions. Metal-catalyzed alkylnitrene C–H insertion is a powerful tool in streamlining their syntheses. Unlike sulfonyl- and aryl-nitrenes, metal-alkylnitrenoid and free singlet alkylnitrene could undergo facile 1,2-hydride shift to form imines.1 A breakthrough was achieved using novel N-heterocyclic carbene Fe(III) porphyrin as catalyst for intramolecular C(sp3)–H amination of alkyl azides, with a broad substrate scope (e.g. primary, secondary and tertiary), up to 95% yield, high regioselectivity (mostly C4–H selective) and applicability to natural product synthesis (tropane, nicotine, cis-octahydroindole and leelamine derivatives).2 Moreover, we have established a precedent in metal-alkylnitrenoid C–H insertion under microwave-assisted condition which tolerates moisture and O2 (≥80% yields for 7 out of 10 examples).

References 1. (a) Aguila, M. J. B.; Badiei, Y. M.; Warren, T. H. J. Am. Chem. Soc. 2013, 135, 9399- 9406. (b) Horner, L.; Christmann, A. Angew. Chem. Int. Ed. 1963, 2, 599-608.

2. Shing, K.-P.; Liu, Y.; Cao, B.; Chang, X.-Y.; You, T.; Che, C.-M. Angew. Chem. Int. Ed. 2018, 57, 11947-11951. (Very Important Paper)

80 Metal Quinoid Carbene Complexes: From Bonding to Catalysis

Hai-Xu Wang and Chi-Ming Che* State Key Laboratory of Synthetic Chemistry and Department of Chemistry, University of Hong Kong, Pokfulam Road, Hong Kong, P. R. China [email protected]

Reactivity study of novel metal carbene complexes can offer new opportunities in catalytic carbene transfer reactions as well as in other synthetic protocols. Metal complexes with quinoid carbene (QC) ligands are assumed to be key intermediates in a variety of catalytic QC transfer reactions developed in recent years. To better understand metal-QC species, we synthesized and characterized a series of Ru(II) porphyrins containing axial QC ligands. The QC ligands exhibit quinonoid structure in both solid and solution states and feature redox non-innocent property. Notably, these Ru-QC complexes display dual reactivity toward carbene transfer reactions with nitrosoarenes (ArNO) and hydrogen atom transfer (HAT) reactions with weak C(sp3)-H and X-H bonds. Detailed mechanistic studies on these reactions have also been undertaken.

Based on the HAT reactivity of metal-QC species, we further developed a synthetic protocol of Ir(III)-catalyzed intermolecular QC insertion reaction into C(sp3)-H bonds which passes through a stepwise radical mechanism and affords C-H arylation products. This methodology is efficient for activated hydrocarbons (down to 40 min reaction time, up to 99% yield, up to 1.0 g scale). Mechanistic studies support the proposed radical mechanism and that the electrophilic Ir(III) center plays a key role in facilitating the radical rebound step.

This work is supported by Hong Kong Research Grants Council and Basic Research Program- Shenzhen Fund. We thank UGC funding administered by the University of Hong Kong.

References 1. Wang, H.-X.; Wan, Q.; Wu, K.; Low, K.-H.; Yang, C.; Zhou, C.-Y.; Huang, J.-S.; Che, C.-M. Ruthenium(II) porphyrin quinoid carbene complexes: synthesis, crystal structure and reactivity toward carbene transfer and hydrogen atom transfer reactions. J. Am. Chem. Soc. 2019, 141, 9027- 9046. 2. Wang, H.-X.; Richard, Y.; Wan, Q.; Zhou, C.-Y.; Che, C.-M. Iridium(III)-catalyzed intermolecular C(sp3)–H insertion reaction of quinoid carbene through a radical mechanism. Angew. Chem. Int. Ed. 2019, accepted. 3. Wu, K.; Cao, B.; Zhou, C.-Y.; Che, C.-M. RhII‐catalyzed intermolecular C−H arylation of aromatics with diazo quinones. Chem. Eur. J. 2018, 24, 4815-4819.

81

CURRICULUM VITAE – Chi-Ming Che

Chair Professor of Chemistry and Head of Department of Chemistry Zhou Guangzhao Professor in Natural Sciences, State Key Laboratory of Synthetic Chemistry and Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, P. R. China Tel: +852 2859 2150 Email: [email protected] Homepage: https://www.chemistry.hku.hk/staff/cmche/cmche.htm

Scientific Vita Since 1983 The University of Hong Kong: Lecturer (1983-1990), Reader (1990-1992), Chair Professor (1992-present), Hui-Wai Haan Chair of Chemistry (1997-2016), and Zhou Guangzhao Professor in Natural Sciences (since 2016).

Research Field Inorganic and Organic Synthesis, Metal-Catalyzed Organic Transformations, Organometallic and Inorganic Photochemistry, Electron Transfer Reactions in Biological Systems, Chiral Metal Catalysts, Asymmetric Organic Oxidations, Green Oxidations, Carbon-Hydrogen Bond Activation and Functionalization, Highly Reactive Metal-Carbon, Metal-Oxygen and Metal-Nitrogen Multiple Bonded Complexes, Luminescent Molecular Materials, Self-Assembled Nanostructured Materials and Coordination Polymers, Bioinorganic Chemistry, and Inorganic Medicines.

Selected Awards and Recognition 1995 Academician, Chinese Academy of Sciences 2006 First Class Prize of the State Natural Science Award of China 2007 Seaborg Lectureship at the University of California at Berkeley 2008 Julia S. and Edward C. Lee Lectureship at University of Chicago 2013 Foreign Associate, National Academy of Sciences, USA 2013 Centenary Prize of Royal Society of Chemistry 2013 Davison Lectureship at Massachusetts Institute of Technology 2015 Founding Member, The Academy of Sciences of Hong Kong 2016 The Huang Yao-Zeng Organometallic Chemistry Award of the Chinese Chemical Society – Lifetime Achievement Award 2016 Ryoji Noyori ACES Award

Representative Publications 1. Reddy, A. R.; Zhou, C.-Y.; Guo, Z.; Wei, J.; Che, C.-M. “ Ruthenium-Porphyrin-Catalyzed Diastereoselective Intramolecular Alkyl Carbene Insertion into C–H Bonds of Alkyl Generated In Situ from N-Tosylhydrazones” Angew. Chem. Int. Ed. 2014, 53, 14175–14180. 2. Zang, C.; Liu, Y.; Xu, Z.-J.; Tse, C.-W.; Guan, X.; Wei, J.; Huang, J.-S.; Che, C.-M. “Highly Enantioselective Iron-Catalyzed cis-Dihydroxylation of Alkenes with Hydrogen Peroxide Oxidant via an FeIII-OOH Reactive Intermediate“ Angew. Chem. Int. Ed. 2016, 55, 10253–10257. 3. Shing, K.-P.; Liu, Y.; Cao, B.; Chang, X.-Y.; You, T.; Che, C.-M. “N-Heterocyclic Carbene Iron(III) Porphyrin-Catalyzed Intramolecular C(sp3)–H Amination of Alkyl Azides” Angew. Chem. Int. Ed. 2018, 57, 11947–11951. 4. Wang, H.-X.; Wan, Q.; Wu, K.; Low, K.-H.; Yang, C.; Zhou, C.-Y.; Huang, J.-S.; Che, C.-M. “Ruthenium(II) Porphyrin Quinoid Carbene Complexes: Synthesis, Crystal Structure, and Reactivitiy toward Carbene Transfer and Hydrogen Atom Transfer Reactions” J. Am. Chem. Soc. 2019, 141, 9027–9046.

82 Studies Toward the Total Synthesis of Pseudolaric Acid B

Baojian Li, Fan Hu, Pauline Chiu* Department of Chemistry, The University of Hong Kong, Hong Kong, P. R. China [email protected]

Pseudolaric acid B is the most potent among the bioactive constituents of tujingpi, a Chinese medicinal herbal preparation used in the treatment of skin fungal infections.1 Besides antifungal activity, it has also been shown to be a microtubule destabilizer, and anti-tumor in vivo. We have been interested in the intramolecular cyclization of metal carbenes with carbonyl groups to generate carbonyl ylides for cycloaddition,2,3 to accomplish the construction of three new bonds in one pot. Using this reaction as the key step, we have achieved the asymmetric synthesis of some natural products, as well as pseudolaric acid A.4,5 Unfortunately, the carbene cyclization cycloaddition step in the proceeded with a low diastereoselectivity of just 1.6:1 for the desired cycloadduct. We have revisited this key step and using alternative chiral rhodium catalysts, we are able to increase the diastereoselectivity of the cycloaddition to 6.0:1. We will report our efforts in a more concise, second-generation synthesis of pseudolaric acid B.

References 1. (a) Wong, V. K. M.; Chiu, P.; Chung, S. S. M.; Chow, L. M. C.; Zhao, Y. Z.; Yang, B. B.; Ko, B. C. B. “Pseudolaric acid B, a novel class of microtubule-destabilizing agent circumvents a multi-drug resistant phenotype, exhibits antitumor activity in vivo” Clin. Cancer Res. 2005, 11, 6002-6011; (b) Leung, L. T.; Ko, B. C. B.; Chiu, P. “Pseudolaric Acids: Isolation, Bioactivity and Synthetic Studies.” Nat. Prod. Rep. 2010, 26, 1066-1083. 2. (a) Shi, B.; Merten, S., Wong, D. K. Y.; Chu, J. C. K.; Liu, L. L.; Lam, S. K.; Jäger, A.; Wong, W.-T.; Chiu, P.; Metz, P. “The Rhodium-Catalyzed Carbene Cyclization Cycloaddition Cascade Reaction of Vinylsulfonates” Adv. Synth. Catal. 2009, 351, 3128- 3132; (b) Groß, T.; Herrmann, T.; Shi, B.; Jäger, A.; Chiu, P.; Metz, P. “Further studies on sultones derived from carbene cyclization cycloaddition cascades” Tetrahedron 2015, 71, 5925-5931. 3. (a) Zhang, X.; Ko, R. Y. Y.; Li, S.; Miao, R.; Chiu, P. “Allenes as dipolarophiles in the intramolecular carbene cyclization cycloaddition cascade reaction” Synlett 2006, 1197-1200; (b) Yu, Y.; Cornelissen, L.; Wong, W.T.; Chiu, P. “Cycloaddition Reactions of Carbonyl Ylides Derived From Enones” Synlett 2015, 26, 1553-1556. 4. (a) Lam, S. K.; Chiu, P. “Total Synthesis of (−)-Indicol” Chem.-Eur. J. 2007, 13, 9589-9599. Leung, L. T.; Chiu, P. “Total Synthesis of (−)-Dolastatrienol” Chem.-Asian J. 2015, 10, 1042-1049. 5. Geng, Z.; Chen, B.; Chiu, P. “Total synthesis of pseudolaric acid A” Angew. Chem. Int. Ed. 2006, 45, 6197-6201. 83

CURRICULUM VITAE – Pauline Chiu

Professor of Chemistry Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, P. R. China Tel: (852) 2859-8949 Email: [email protected] Homepage: www.pchiu.chemistry.hku.hk

Scientific Vita Since 2011 The University of Hong Kong, Professor, Department of Chemistry Since 2019 Organic Letters, Associate Editor, American Chemical Society 2007-2011 The University of Hong Kong, Associate Professor, Department of Chemistry 2001-2007 The University of Hong Kong, Assistant Professor, Department of Chemistry 1996-2001 The University of Hong Kong, Research Fellow, Department of Chemistry 1994-1995 Columbia University, Postdoctoral Fellow, with Samuel J. Danishefsky 1990-1994 University of Toronto, Ph. D., with Mark Lautens 1988-1990 University of Toronto, M. Sc., with Adrian G. Brook 1984-1988 University of Toronto, B. Sc. (Honours) in Chemistry

Research Field Development of novel reactions: copper-mediated transformations, carbene chemistry, cycloadditions; Natural product total synthesis; Medicinal chemistry

Selected Awards and Recognition 2003 Society of Synthetic Organic Chemistry Summer Symposium Lectureship Award 2007 The University of Hong Kong Research Output Prize 2014 The Asian Core Program Lectureship Award from Japan, sponsored by JSPS 2011 Fellow, Royal Society of Chemistry

Representative Publications 1. Krenske, E. H.; Lam, S.; Ng, J. P. L.; Lo, B.; Lam, S. K.; Chiu, P.; Houk, K. N. “Concerted Ring-Opening and Cycloaddition of Chiral Epoxy Enolsilanes with Dienes.” Angew. Chem. Int. Ed. 2015, 54, 7422–7425. 2. Ling, J.; Lam, S.; Low, K.H.; Chiu, P. “Dearomative Intramolecular (4+3) Cycloadditions of Arenes with Epoxy and Aziridinyl Enolsilanes.” Angew. Chem. Int. Ed. 2017, 56, 8879– 8882. 3. Li, Z.; Lam, S. M.; Ip, I.; Wong, W. T.; Chiu, P. “Rearrangements of -Diazo--hydroxy- ketones for the synthesis of bicyclo[m.n.1]alkanones” Org. Lett. 2017, 19, 4464–4467. 4. Lam. S. M.; Wong, W. T.; Chiu, P. “An approach to the welwistatin core via a diazoketone rearrangement-ring expansion strategy.” Org. Lett. 2017, 19, 4468–4471. 5. Zhang, X. X.; Ko, R. Y. Y.; Xie, X. Q.; Qi, W. P.; Li, P. C.; Chiu, P. “Application of a Rhodium-catalyzed Cyclization Cycloaddition Cascade Strategy to the Total Synthesis of (−)-Curcumol” Org. Chem. Front., 2018, 5, 1092–1095. 6. Ng., E. W. H.; Low, K.H.; Chiu, P. “Synthesis and Applications of Unquaternized C-bound Boron Enolates” J. Am. Chem. Soc. 2018, 140, 3537–3541.

84 Modular and Efficient Synthesis of Highly Functionalized 5-Fluoropyridazines by a (2+1)/(3+2)-Cycloaddition Sequence

Gael Tran, Domingo Gomez Pardo, Tomoki Tsuchiya, Stefan Hillebrand, Jean-Pierre Vors, Janine Cossy Molecular, Macromolecular Chemistry and Materials, ESPCI Paris, CNRS, PSL University, 10 rue Vauquelin, 75231 Paris Cedex 5, France

[email protected]

Pyridazines are important heterocycles that have recently found a broad range of applications in pharmaceutical, agrochemical and material industries,1 and in addition, a surge of interest for pyridazines has recently appeared among medicinal chemists.2 Furthermore, due to the considerable benefits that can be brought by a fluorine atom on the pharmacodynamics and pharmacokinetic properties of a compound, and in light of the recent recognition received by pyridazines, we have develop a method to access a diversity of substituted fluoropyridarznes. Herein, we will described an easy access to 5-fluoropyridazines by a (2+1)/(3+2)-cycloaddition sequence between terminal akynes, a difluorocarbene and a diazo compound. The synthesis of 5-fluoropyridazines, using this sequence of reactions, does not necessitate the isolation of any intermediates. It is worth mentioning that the obtained 5-fluoropyridazines were a good platform to access highly diversified pyridazines.3

References 1. For ex see: a) Amoo, V. E.; Harrisson, C. R.; Lahm, G. P.; Lowder, P. D.; Stevenson, T. M.; Lo,ng, J. K.; Shapiro, R.; March, R. W.; Allen, D. E.; Richmond, M. D.; March, W. A.; Chun, G.; Folgar, M. P.; Griswold, S. M. In Synthesis and Chemistry of Agrochemicals, Baker, D. R.; Fenyes, J. G.; Lahm, G. P.; selby, T. P.; Stevenson, T. M., Eds; American Chemical Society: Washington, DC, 2001; Vol. 6 pp 156-165. 2. Wermuth, C. G. “Are pyridazines privileged structures ?” Med. Chem Commun. 2011, 2, 935-941. 3. Tran, G.; Gomez Pardo, G.; Tsuchiya, T.; Hillebrand, S.; Vors, J. P.; Cossy, J. “Modular, concise, and efficient synthesis of highly functionalized 5-fluoropyridazines by a (2+1)/(3+2)-cycloaddition sequence” Org. Lett. 2015, 17, 3414- 3417.

Acknowledgement Bayer S.A.S. is acknowledged for financial support

85 Synthesis of New Perfluorinated Surfactants Affording Highly Stable Aqueous Liquid Foams

Maria Russo,1,2 Zacharias Amara,1 Johan Fenneteau,1 Pauline Chaumont-Olive,1 Ilham Maimouni,1,2 Patrick Tabeling,2 and Janine Cossy1 1 Molecular, Macromolecular Chemistry and Materials, ESPCI Paris, CNRS, PSL University, 10 rue Vauquelin, 75231 Paris Cedex 5, France 2 Microfluidique, MEMS et Nanostructures, Institut Pierre-Gilles de Gennes, ESPCI Paris, CNRS, PSL University, 75231 Paris Cedex 5, France. [email protected]

The production of liquid foams exhibiting well-defined structures and long-term stability is a key challenge in material design and specially to develop new material bearing photonic band gap properties.1-3 Even if commercially available surfactants such as SDS or lutensol provides high foamability, these compounds are not stable for more than a few hours. In this field, new classes of pyridium amphiphilic compounds were synthetized from simple building blocks. A particular formulation of these compounds in water via a tailor-made microfluidic device allowed us to produce 3D-foams. This set-up also afforded a unique in situ characterization of the colloid dynamics such as aging effects (coalescence, coarsening), therefore setting useful references for future applications.

Spacer = reactive unit

OH O

O R

N+ X- Lipophilic part R’

Hydrophilic head

References 1. Weaire, D.; Hutzler, S. « The physics of Foams, Clarendon » Press: Oxford, Royaume-Uni de Grande-Bretagne et d’Irlande du Nord, 1999. 2. Cantat, I. “Foams: Structure and Dynamics”, 2013. 3. Ricouvier, J.; Tabeling, P.; Yazhgur, P. “Foam as a Self-Assembling Amorphous Photonic Band Gap Material” Proc Natl Acad Sci USA 2019, 9202–9207.

Acknowledgement

The Microflusa project (664823) is funded by the European Union’s Horizon 2020 Programme

86

CURRICULUM VITAE – Janine Cossy

Professor of Chemistry Laboratory Molecular, Macromolecular Chemistry and Materials (C3M) ESPCI Paris 10 rue Vauquelin 75231 Paris Cedex 05 France Tel: +33 (0)1 40 79 44 29 Email: [email protected] Homepage: http://lco.espci.fr

Scientific Vita 1990 - ESPCI Paris, Professor of Organic Chemistry 1992-2013 Director of the CNRS Unity (UMR 8231), ESPCI Paris 1990 University of Champagne-Ardenne, Reims (France), Director of Research at the CNRS 1976-1990 University of Champagne-Ardenne, Reims (France), Research Assistant at the CNRS 2008 - Vice-President of Acanthe-Biotech

Research Field Coupling reactions, catalysis, enantioselecivity, carbene chemistry, cycloaddition, ring expansion, natural product synthesis, enzymatic reactions.

Selected Awards and Recognition 1987 CNRS Bronze Medal 1996 Junfleish Award from the French Academy of sciences 1996 CNRS Silver Medal 1997 Chevalier de l’Ordre National du Mérite 2005: UK Royal Society Rosalyn Francklin International Lecturership awarded to internationally recognized women scientists (UK) 2009 Le Bel Award of the French Chemical Society 2009 JSPS Fellow, University of Tokyo, Tokyo (Japan) 2013 Chevalier de la Légion d’Honneur 2015 E. C. Taylor Senior Award (USA) 2015 UR Ghatak Endowment Award (India) 2017 Member of the French Academy of sciences 2016 Tarrant Professorship, University of Florida (USA) 2018 Promoted Officier de l’Ordre National du Mérite (France) 2018 Award of Professor PC RAY Chair from the Indian National Science Academy (India) 2018 Fellow of the American Chemical Society 2019 IUPAC 2019 Distinguished Women in Chemistry or Chemical Engineering

Representative Publications 1. Krieger, J. P.; Lesuisse, D.; Ricci, G.; Perrin, M.-A.; Meyer, C.; Cossy, J. “Rhodium(III)-catalyzed C-H activation/heterocyclization as a macrocyclization strategy. Synthesis of pyridinones” Org. Lett. 2017, 19, 2706-2709. 2. Escudero, J.; Bellosta, V.; Cossy, J. “Rhodium-catalyzed cyclization of unsaturated alkoxyamines: An unexpected formation of oxygen-containing heterocycles” Angew. Chem. Int. Ed. 2018, 57, 574-578. 3. Lecourt, C.; Dhambri, S.; Yamani, K.; Boissonnat, G.; Specklin, S.; Fleury, E.; Auclair, E.; Sable, S.; Sautel, F.; Massiot, G.; Meyer, C.; Cossy, J.; Sorin, G.; Lannou, M-I.; Ardisson, J. “Total synthesis of a stereoisomer of hemicalide” Chemistry: a European Journal . 2019, 25, 2745. 4. Anderssen, C.; Ferey, V.; Daumas, M.; Bernardelli, P.; Guérinot, A.; Cossy, J. “Introduction of cyclopropyl and cyclubutyl ring on alkyl iodides through cobalt-catalyzed cross-coupling” Org. Lett. 2019, 21, 2285. 87 Construction of Non-planar N-Heterocycles through Cascade Processes Triggered by N-Aryl Nitrene Formation

Tom G. Driver, Tianning Deng and Wrickban Mazumdar Department of Chemistry, University of Illinois at Chicago, Chicago, IL 60607 [email protected]

Our laboratory has actively pursued the development of transition metal-catalyzed N-heterocycle formation from azides and nitroarenes (Scheme 4). We established that Rh2(II)-carboxylates catalyze the conversion of aryl azides into diverse N-heterocycles through selective C–H bond amination. Data from our initial systems indicated that C–N bond formation occurred through a unique electrocyclization-migration mechanism, which enabled access to non-planar N- heterocycles. This discovery sparked new reaction development by targeting alternative electrophilic metal N-aryl catalytic intermediates, and we showed that analogous domino reactions could be triggered from nitroarenes. We established that the electrophilic reactivity embedded in nitroarenes can be unlocked using Mo(CO)6 and a palladium catalyst to form functionalized 3H- indoles by controlling the reactivity of in situ generated nitrosoarene intermediates. Together these proved that electrophilic nitrogen species could be accessed under reductive or redox neutral conditions. We were curious if these electrophilic species could be generated from through oxidation, and we report our work towards identifying the optimal conditions to in situ oxidatively generate N-aryl nitrenoids and exploit their ability to trigger cascade reactions.

References 1. Jana, N.; Zhou, F.; Driver, T. G. Promoting Reductive Tandem Reactions of Nitrostyrenes with Mo(CO)6 and a Palladium Catalyst To Produce 3H-Indoles. J. Am. Chem. Soc. 2015, 137, 6738-6741. 2. Kong, C.; Jana, N.; Jones, C.; Driver, T. G. “Control of the Chemoselectivity of Metal N-Aryl Nitrene Reactivity: C–H Bond Amination versus Electrocyclization.” J. Am. Chem. Soc. 2016, 138, 13271-13280. 3. Mazumdar, W.; Jana, N.; Thurman, B. T.; Wink, D. J.; Driver, T. G. “Rh2(II)- Catalyzed Ring Expansion of Cyclobutanol-Substituted Aryl Azides To Access Medium-Sized N-Heterocycles.” J. Am. Chem. Soc. 2017, 139, 5031-5034.

88

CURRICULUM VITAE – Tom G. Driver

Professor of Chemistry Department of Chemistry University of Illinois at Chicago 845 West Taylor Street Chicago, IL, 60607 Tel: 001 (312) 996-9672 Email: [email protected] Homepage: www2.chem.uic.edu/driver

Scientific Vita Since 2017 Professor, University of Illinois at Chicago Since 2018 UI Cancer Center, Translational Oncology Since 2012 Core Leader, Chemical Libraries, UICentre for Drug Discovery 2015 – 2018 Special Invited Professor, Huaqiao University, Xiamen, People’s Republic of China 2012 – 2017 Associate Professor, University of Illinois at Chicago. 2006 – 2012 Assistant Professor, University of Illinois at Chicago 2004 – 2006 NIH Postdoctoral Fellow. California Institute of Technology

Research Field Organic synthetic methods; catalytic reactions with metal divalent intermediates. Medicinal Chemistry; pulmonary arterial hypertension (NAMPT); sleep apenia (CSE), biofilms (PepO)

Awards and Recognition 2014 UIC LAS Award for Faculty in Sciences 2015 UIC Graduate College Graduate Mentor Award 2015 Fujian 100 Talents Plan Designate, People’s Republic of China 2016 Top Tier Foreign Expert, People’s Republic of China 2018 Overseas Chair, Shanghai Institute of Technology

Representative Publications 1. “Control of the Chemoselectivity of Metal N-Aryl Nitrene Reactivity: C–H Bond Amination versus Electrocyclization.” Kong, C.; Jana, N.; Jones, C. Driver, T. G. J. Am. Chem. Soc. 2016, 138, 13271- 13280. 2. “Intermolecular Pd-Catalyzed Aryl C–H Bond Aminocarbonylation using Nitroarenes and Mo(CO)6.” Zhou, F.; Wang, D.-S.; Guan, X.; Driver, T. G. Angew. Chem. Int. Ed. 2017, 56, 4530-4534. 3. “Rh2(II)-Catalyzed Ring Expansion of Cyclobutanol-Substituted Aryl Azides to Access Medium- Sized N-Heterocycles.” Mazumdar, W.; Jana, N.; Thurman, B. T.; Driver, T. G. J. Am. Chem. Soc., 2017, 139, 5031-5034. 4. “Intramolecular Pd-Catalyzed Reductive Amination of Enolizable sp3-C–H Bonds.” Ford, R. L.; Alt, I.; Jana, N.; Driver, T. G. Org. Lett. 2019, 21, 8827-8831. 5. "Nicotinamide Phosphoribosyltransferase Inhibitors and Methods for Use of the Same." Driver, T. G.; Guan, X.; Mazumdar, W.; Su. N.; Ratia, K.; Hickok, J.; Lockett, A. D.; Machado, R. International Patent Application No. PCT/US2019/016684 filed 2-16-2019, published 8-8-2019.

89

Synthesis of Heterocyclic Compounds by Ruthenium-Catalyzed Nitrene Transfer Reactions to Unsaturated Hydrocarbons

Caterina Damiano, Paolo Sonzini and Emma Gallo Department of Chemistry, University of Milan, 20133 Milan, Italy [email protected]

During our ongoing studies on the use of azides as nitrene sources, we discovered that aryl azides, besides being reactive towards double bonds forming aziridines, they also react with triple bonds yielding indoles,1 rather than triazoles. These valuable fine-chemicals can easily be obtained in the presence of ruthenium porphyrin catalysts by a very atom-efficient procedure, which produces benign molecular nitrogen as the only by-product. The mechanism of the ruthenium-catalyzed one-pot formation of indoles was investigated by applying a symbiotic experimental/theoretical approach. This mechanistic study was fundamental for shedding light on the structure of possible catalytic intermediates as well as optimizing reaction performances. In view of the general applicability of the Ru(porphyrin)CO-based catalytic methodology in the synthesis of aziridines, we started studying their 100 % atom-efficient transformation into 2 N-aryl oxazolid-2-ones by CO2 cycloaddition. We discovered that the reaction was very well mediated by a porphyrin/TBAX binary system (TBAX = tetrabutyl ammonium salt), and the presence of a transition metal promoter was not required. The synthesis of N-aryl oxazolid-2-ones occurred with excellent regioselectivities, forming 5-substituted products A as the major compounds. In addition, the procedure sustainability was improved by applying a catalytic tandem reaction, in which aziridines were first synthesized and then reacted with CO2 without being isolated nor purified.

twenty N-aryl oxazolid-2-ones

thirty

C3-substituted indoles

References 1. Intrieri, D.; Carminati, D. M.; Zardi, P.; Damiano, C.; Manca, G.; Gallo, E.; Mealli, C. “Indoles from Alkynes and Aryl Azides. Scope and Theoretical Assessment of Ruthenium Porphyrin-Catalyzed Reactions” Chem. Eur. J. 2019 doi.org/10.1002/chem.201904224. 2. Sonzini, P.; Damiano, C.; Intrieri, D.; Gallo E. “A Metal-free Synthesis of N-aryl Oxazolidin-2-ones by the One pot Reaction of CO2 with N-aryl Aziridines.” Submitted.

90

CURRICULUM VITAE – Emma Gallo

Associate Professor of Chemistry Department of Chemistry of Milan University, 20133 Milan, Italy Tel: +39 (02) 5031-4374 Email: [email protected] Homepage: https://www.unimi.it/en/ugov/person/emma-gallo

Scientific Vita Since 2005 University of Milan (I), Associate Professor, Department of Chemistry 2001-2005 Assistant Professor at University of Milan (I) 1998-2001 Research Associate at University of Milan (Italy) 1997-1998 Post-doctoral Fellowship at University of Milan (Italy) 1996-1997 Maitre Assistant at University of Lausanne (CH) 1991-1996 PhD in Chemistry at University of Lausanne (CH) (supervisor: Prof. C. Floriani)

Research Fields i) Development of eco-compatible syntheses of fine chemicals by carbene and nitrene transfer reactions to hydrocarbons. ii) Valorization of CO2 as C1 renewable raw material to produce high added-value compounds. iii) Heterogenization of homogeneous catalysts. iv) Synthesis of chemosensors for detecting emerging pollutants and food contaminants.

Selected Awards and Recognition Since 2015: Vice-President of the Inorganic Division of the Italian Chemical Society (SCI). 2013 and 2017: National Academic Qualification as Full Professor.

Representative Publications 1. Intrieri, D.; Carminati, D. M.; Zardi, P.; Damiano, C.; Manca, G.; Gallo, E.; Mealli, C. “Indoles from Alkynes and Aryl Azides. Scope and Theoretical Assessment of Ruthenium Porphyrin-Catalyzed Reactions” Chem. Eur. J. 2019 doi.org/10.1002/chem.201904224. 2. Damiano, C.; Gadolini, S.; Intrieri, D.; Lay, L.; Colombo, C.; Gallo, E. “Iron and Ruthenium Glycoporphyrins: Active Catalysts for the Synthesis of Cyclopropanes and Aziridines” Eur. J. Inorg. Chem. 2019, 4412-4420. 3. Carminati, D.; Gallo, E.; Damiano, C.; Caselli, A.; Intrieri. D. “Ruthenium Porphyrin-Catalyzed Synthesis of Oxazolidinones by Cycloaddition of CO2 to Aziridines” Eur. J. Inorg. Chem. 2018, 5258-5262. 4. Carminati, D. M.; Intrieri, D.; Caselli, A.; Le Gac, S.; Boitrel, B.; Toma, L.; Legnani, L.; Gallo, E. “Designing ‘Totem’ C2-Symmetrical Iron Porphyrin Catalysts for Stereoselective Cyclopropanations” Chem. Eur. J. 2016, 22, 13599-13612.

91 Carbene or Proton Transfer Reactions – Accessing the Reactivity of Diazoalkanes via Photoexcitation

Rene M. Koenigs Institute of Organic Chemistry, RWTH Aachen University, 52074 Aachen, Germany [email protected]

The protonation reaction of with acidic carboxylic acids to provide methyl esters is an important reaction with many applications in chemical synthesis. In this textbook example diazomethane reacts as a base in an initial acid-base reaction with the .[1] A different reactivity mode of diazoalkanes can be accessed using metal catalysts[2] or photochemical conditions,[3] which proceeds via metal-carbene or free carbene intermediates. Today, the carbene reactivity of diazoalkanes is an important strategy to conduct highly efficient cycloaddition, rearrangement, X-H, or C-H functionalization reactions. Herein, we report on our recent findings on the carbene reactivity of aryldiazoacetates under photochemical conditions that react with group VI elements under ylide formation in rearrangement and intercepted rearrangement reactions,[4,5] which were studied in detail by DFT calculations for an understanding of the reaction mechanism of the rearrangement process of oxygen and sulfur ylides.[5] We conclude with our latest findings on the reactivity of aryldiazoacetates that form an unreactive hydrogen-bonding complex with mildly acidic fluorinated alcohols. Upon photoexcitation of this complex, a photoinduced proton transfer occurs that allows now mild O- H functionalization reactions under stoichiometric conditions in high yields.[6]

References 1. Brückner, R.; Organic Mechanisms: Reactions, Stereochemistry and Synthesis, Springer, 2010, p.93-94. 2. a) Davies, H. M. L.; Manning, J. R. Nature 2018, 451, 417-424; b) Ford, A.; Miel, H.; Ring, A.; Slattery, C. N.; Maguire, A. R.; McKervey, M. A. Chem. Rev. 2015, 115, 9981-10080. 3. a) Empel, C.; Koenigs, R. M. Synlett 2019, 30, 1929-1934. 4. a) Hommelsheim, R.; Guo, Y.; Yang, Z.; Empel, C.; Koenigs, R. M.; Angew. Chem. Int. Ed. 2019, 58, 1203-1207; b) a) Yang, Z.; Guo, Y.; Koenigs, R. M. Chem. Eur. J. 2019, 25, 6703- 6707; c) F. He; Pei, C.; Koenigs, R. M. manuscript submitted. 5. Jana, S.; Yang, Z.; Pei, C.; Xu, X.; Koenigs, R. M.; Chem. Sci. 2019, 10, 10129-10134. 6. Jana, S.; Yang, Z.; Li, F.; Empel, C.; Ho, J., Koenigs, R. M. ChemRxiv, 2019, DOI: 10.26434/chemrxiv.10317947.v1.

92 Blue Light Induced Carbene Transfer Reactions

Claire Empel and Rene M. Koenigs Institute of Organic Chemistry, RWTH Aachen University, 52074 Aachen, Germany [email protected]

Diazoalkanes are a common carbene precursor for carbene transfer reactions enabling cycloaddition, rearrangement or, C-H and X-H insertion reactions. Most often, these reactions are catalyzed by transition metals via metal carbenes generated from the diazoalkanes.[1] Metal- free approaches involve the thermal generation of the free carbene or the photolysis by irradiation with light, yet current methods are hampered due to side-reactions caused by high temperatures or the application of high energy UV-light for the photolysis of the diazoalkane.[2] Only recently, the photolysis of diazoalkanes, which are usually intensely colored, using visible light attracted the interest of synthetic chemistry.[3,4] In this context, we reported on our studies towards the photochemical generation of carbenes form diazoalkanes using low-energy blue light. This operationally simple protocol allows highly efficient cyclopropenation reactions of a broad range of alkynes with excellent yields without the need to exclude air or moisture.[4] Additionally, cyclopropanation reactions and Doyle-Kirmse rearrangement reactions were studied using a continuous-flow setup.[5] Moreover, we investigated the in situ generation of diazoalkanes via Bamford-Stevens reaction from tosyl hydrazones. Following this approach, the stoichiometric C-H functionalization of indole heterocycles and N-H insertion reactions were investigated.[6] a.) Blue Light Induced Cyclopropenation Reaction R’ Ph CO2Me Photolysis Cyclopropenation reaction N2 CO Me R 2 31 examples, up to 99% yield [2+1] cycloadditon R R' Ph CO2Me - N2 reaction free carbene b.) Generation of Free Carbenes via Bamford-Stevens Reaction

NTsH C-H functionalization Bamford-Stevens N2 N Photolysis 27 examples, up to 86% yield reaction CO2Me CO Me CO2Me 2 - N2 N-H insertion reactions 11 examples, up to 71% yield diazoalkane free carbene

References 1. a) Davies, H. M. L.; Manning, J. R. Nature 2018, 451, 417-424; b) Ford, A.; Miel, H.; Ring, A.; Slattery, C. N.; Maguire, A. R.; McKervey, M. A. Chem. Rev. 2015, 115, 9981-10080. 2. a) Ciszewski, L. W.; Rybicka-Jasi�ska, K.; Gryko, D. Org. Biomol. Chem. 2019, 17, 432- 448; b) Empel, C.; Koenigs, R. M. Synlett 2019, 30, 1929-1934. 3. a) Jurberg, I.; Davies, H. M. L. Chem. Sci. 2018, 9, 5112-5118; b) Xiao, T.; Mei, M.; He, Y.; Zhou, L. Chem. Commun. 2018, 54, 8865-8868. 4. Hommelsheim, R.; Guo, Y.; Yang, Z.; Empel, C.; Koenigs, R. M.; Angew. Chem. Int. Ed. 2019, 58, 1203-1207. 5. Empel, C.; Koenigs, R. M. J. Flow Chem. 2019, manuscript accepted. 6. Jana, S.; Li, F.; Empel, C.; Verspeek, D.; Aseeva, P.; Koenigs, R. M.; manuscript submitted.

93

CURRICULUM VITAE – Rene M. Koenigs

Assistant Professor of Organic Chemistry Institute of Organic Chemistry, RWTH Aachen University, 52074 Aachen, Germany Tel: 0049 (175) 1021 476 Email: [email protected] Homepage: http://www.koenigslab.rwth-aachen.de

Scientific/Professional Vita Since 2015 RWTH Aachen University, Assistant Professor, Institute of Organic Chemistry 2018-2020 UNSW Sydney, Visiting Professor, School of Chemistry 2013-2015 Grünenthal GmbH, Head of Laboratory, Medicinal Chemistry 2011-2013 Grünenthal GmbH, Postdoc, Medicinal Chemistry

Research Field Photochemistry, carbene transfer reactions, metal-free carbene chemistry, reactions of diazo compounds, cycloaddition, rearrangement, synthetic methodology

Selected Awards and Recognition 2016 RWTH Start-Up 2017 Thieme Journal Award 2018 Boehringer Ingelheim Exploration Grant 2018 Dean’s Seed Fund 2019 Dr. Otto Roehm Stiftung

Representative Publications 1. Hommelsheim, R.; Guo, Y.; Yang, Z.; Empel, C.; Koenigs, R. M. “Blue Light Induced Carbene Transfer Reactions of Diazoalkanes” Angew. Chem. Int. Ed. 2019, 58, 1203-1207; Angew. Chem. 2019, 131, 1216-1220. 2. Hock, K. J.; Knorrscheidt, A.; Hommelsheim, R.; Ho, J.; Weissenborn, M. J.; Koenigs, R. M. “Tryptamine synthesis by iron-porphyrin catalyzed C—H functionalization of indole with diazoacetonitrile” Angew. Chem. Int. Ed. 2019, 58, 3630-3634; Angew. Chem. 2019, 131, 3669- 3673. 3. Jana, S.; Yang, Z.; Pei, C.; Xu, X.; Koenigs, R. M. “Photochemical ring expansion reactions: synthesis of tetrahydrofuran derivatives and mechanism studies” Chem. Sci. 2019, 10, 10129-10134. 4. Jana. S.; Yang, Z.; Li, F.; Empel, C.; Ho, J.; Koenigs, R. M. “Photoinduced Proton Transfer Reactions for Mild O-H Functionalization Reactions of Unreactive Alcohols” ChemRxiv 2019, DOI: 10.26434/chemrxiv.10317947.v1 5. Jana, S.; Koenigs, R. M. “Catalytic sigmatropic rearrangement reactions of selenium ylides via carbene transfer reactions” Org. Lett. 2019, 21, 3653-3657.

94 Stereoselective Rhodium-Catalyzed Styrene Aziridination: A Mechanistic Study

Hélène Lebel Department of Chemistry and Centre in Green Chemistry and Catalysis (CGCC), Université de Montréal, Montréal, Québec, H3C 3J7, Canada [email protected]

The stereoselective, rhodium-catalyzed aziridination of styrene derivatives with a chiral N-mesyloxycarbamate was found to be highly substrate dependent. A density functional theory (DFT) study was performed to elucidate the stereochemical outcome of the aziridination process. Rhodium acetate was initially used as a model catalyst, followed by computational studies conducted with Rh2[(S)-nttl]4. Both singlet and triplet rhodium nitrene species were identified as intermediates affording concomitant concerted and radical pathways. In the latter case, the radical intermediate appears to undergo a direct ring closure via a minimum energy crossing point (MECP) between the triplet and closed-shell singlet surfaces. Exceptionally for the m-Br-styrene aziridination, an alternative radical pathway with a carbon-carbon bond rotation was observed, accounting for the observed 74:26 mixture of diastereomers.

The computational analysis also suggests little control of the metal nitrene conformation with Rh2(OAc)4 with the chiral N-mesyloxycarbamate: two conformers were located affording two diastereomers of the aziridine and correlating our experimental results. On the other hand, only one conformer was found for the nitrene generated from the chiral N-mesyloxycarbamate and Rh2[(S)-nttl]4. The so-called “all-up” conformer of Rh2[(S)-nttl]4 was not only the most stable metal nitrene species, but also afforded the lowest energy transition state. The calculated dr for p-Br-styrene aziridination agrees with the observed experimental result. The combination of experimental and computational results offers a detailed mechanistic picture, providing insights for further catalyst development to enhance reactivity and selectivity.

References 1. Azek, E.; Spitz, C.; Ernzerhof, M.; Lebel, H. “A Mechanistic Study of the Stereochemical Outcomes of Rhodium‐Catalysed Styrene Aziridinations” Adv. Synth. Catal. 2020, Accepted Author Manuscript. doi:10.1002/adsc.201901184. 2. Azek, E.; Khalifa, M.; Bartholomeus, J.; Ernzerhof, M.; Lebel, H. “Rhodium(II)-catalyzed C-H aminations using N-mesyloxycarbamates: reaction pathway and by-product formation” Chem. Sci. 2019, 10, 718-729. 3. Lebel, H.; Spitz, C.; Leogane, O.; Trudel, C.; Parmentier, M. “Stereoselective Rhodium- Catalyzed Amination of Alkenes” Org. Lett. 2011, 13, 5460-5463.

95

CURRICULUM VITAE – Hélène Lebel

Professor of Chemistry Department of Chemistry and Centre in Green Chemistry and Catalysis, Université de Montréal, Montréal, Québec, H3C 3J7, Canada Tel: 001 (514) 343-5826 Email: [email protected] Homepage: https://www.helenelebellab.com/

Scientific Vita Since 2010 Université de Montréal, Professor, Department of Chemistry 2005-2010 Université de Montréal, Associate Professor, Department of Chemistry. 1999-2005 Université de Montréal, Assistant Professor, Department of Chemistry. 1998-1999 Harvard University, Postdoctoral Fellow, Department of Chemistry and Chemical Biology

Research Field Synthetic methodologies; transition metal catalyzed-processes; metal nitrene species, continuous flow technology.

Selected Awards and Recognition 2001 Boehringer Ingelheim Young Investigator Award (American Chemical Society) 2004 Ichikizaki Fund for Young Chemists Award 2005 Enantioselective Synthetic Chemistry Research Award 2008 Johnson & Johnson Focused Funding Grant Award 2009 Merck Frosst Centre for Therapeutic Research Award (Canadian Society for Chemistry) 2011 Canada Research Chair in Organometallic Catalysis 2014 Clara Benson Award (Canadian Society for Chemistry)

Representative Publications 1. Lai, C.; Mathieu, G.; Gabrielli Tabarez, L. P.; Lebel, H. “Batch and Continuous-Flow Iron(II)-Catalyzed Synthesis of Sulfilimines and Sulfoximines using N-Mesyloxy- carbamates” Chem. Eur. J. 2019, 25, 9423-9426. 2. Audubert, C.; Bouchard, A.; Mathieu, G.; Lebel, H. “Chemoselective Synthesis of Amines from Ammonium Hydroxide and Hydroxylamine in Continuous Flow” J. Org. Chem. 2018, 83, 14203-14209. 3. Lebel, H.; Mamani Laparra, L.; Khalifa, M.; Trudel, C.; Audubert, C.; Szponarski, M.; Dicaire Leduc, C.; Azek, E.; Ernzerhof, M. “Synthesis of Oxazolidinones: Rhodium-Cata- lyzed C-H Amination of N-Mesyloxycarbamates” Org. Biomol. Chem. 2017, 15, 4144-4158. 4. Audubert, C.; Lebel, H. “Mild Esterification of Carboxylic Acids via Continuous Flow Diazotization of Amines” Org. Lett. 2017, 19, 4407-4410. 5. Audubert, C.; Gamboa Marin, O. J.; Lebel, H. “Batch and Continuous-Flow One-Pot Processes using Diazotization to Produce Silylated Diazo Reagents.” Angew. Chem., Int. Ed. 2017, 56, 6294-6297.

96 Ruthenium-Porphyrin-Based Metal-Organic Frameworks as Recyclable Heterogeneous Catalysts for Carbene Transfer Reactions Yuan Wu, Chen Yang, Vanessa Kar-Yan Lo, Chi-Ming Che* State Key Laboratory of Synthetic Chemistry and Department of Chemistry, University of Hong Kong, Pokfulam Road, Hong Kong, P. R. China [email protected], [email protected]

Ruthenium(II) porphyrin complexes have robust catalytic activity towards various atom and/or group transfer reactions. In order to develop the next generation of practical catalytic systems suitable for organic synthesis in industrial scale, we have prepared a series of ruthenium- porphyrin-based metal-organic frameworks (MOFs), and their heterogeneous catalytic properties towards carbene transfer reactions were studied.

Among the 5 ruthenium(II)-porphyrin-based MOFs prepared, Ru-MOF-Zr showed the best stability under ambient conditions, and the best catalytic activity towards intermolecular cyclopropanation of styrene derivatives with ethyl diazoacetate (EDA). Compared to its homogeneous counterpart, the heterogeneous Ru-MOF-Zr excels in terms of (1) easy separation from the reaction mixture; (2) recyclability of the catalyst; and (3) size selectivity of the styrene substrates brought by the finite-sized pores of the MOF structure. The same catalyst was also active towards intramolecular cyclopropanation of allylic diazoacetates and diazo coupling reactions.

This work is financially supported by Innovation and Technology Commission (HKSAR, China) to the State Key Laboratory of Synthetic Chemistry, and The University of Hong Kong.

References 1. Zhou, C.-Y.; Huang, J.-S.; Che, C.-M. “Ruthenium-Porphyrin-Catalyzed Carbenoid Transfer Reactions” Synlett 2010, 2681-2700. 2. Che, C.-M; Lo, V. K.-Y.; Zhou, C.-Y.; Huang, J.-S. “Selective Functionalization of Saturated C–H Bonds with Metalloporphyrin Catalysts” Chem. Soc. Rev. 2011, 40, 1095-1975.

97

CURRICULUM VITAE – Vanessa Kar-Yan Lo

Research Officer State Key Laboratory of Synthetic Chemistry and Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, P. R. China Tel: +852-2241-5811 Email: [email protected]

Scientific Vita Since 2009 The University of Hong Kong: Research Assistant (2009), Research Associate (2009), Postdoctoral Fellow (2010-2016), and Research Officer (2016-present). 2018 Westfälische Wilhelms-Universität Münster, Germany: Visiting Postdoctoral Fellow. 2013-2014 Westfälische Wilhelms-Universität Münster, Germany: Visiting Postdoctoral Fellow. 2008-2009 The Hong Kong Polytechnic University: Research Assistant (2008), Part-time Research Assistant (2009).

Research Field Development of transition metal-catalyzed reactions and applications on organic synthesis

Representative Publications 1. Lo, V. K.-Y.; Chan, Y.-M.; Zhou, D.; Toy, P. H.; Che, C.-M. “Highly Enantioselective Synthesis Using Prolinol as Chiral Auxiliary. Silver-Mediated Synthesis of Axially Chiral Vinylallenes and Subsequent (Hetero)-Diels-Alder Reactions” Org. Lett. 2019, 21, 7717–7721. 2. Lam, T.-L..; Tong, K.-C.; Yang, C.; Kwong, W.-L.; Guan, X.; Li, M.-D.; Lo, V. K.-Y.; Chan, S. L.- F.; Phillips, D. L.; Lok, C.-N.; Che, C.-M. “Luminescent ruffled iridium(III) porphyrin complexes containing N-heterocyclic carbene ligands: structures, spectroscopies and potent antitumor activities under dark and light irradiation conditions” Chem. Sci. 2019, 10, 293-309. 3. Chan, K.-H.; Guan, X.; Lo, V. K.-Y.; Che, C.-M. “Elevated Catalytic Activity of Ruthenium(II) Porphyrin-Catalyzed Carbene / Nitrene Transfer and Insertion Reactions with N-Heterocyclic Carbene Ligand” Angew. Chem. Int. Ed. 2014, 53, 2982-2987. 4. Wang, J.-C.; Zhang, Y.; Xu, Z.-J.; Lo, V. K.-Y.; Che, C.-M. “Enantioselective Intramolecular Carbene C–H Insertion Catalyzed by a Chiral Iridium(III) Complex of D4-Symmetric Porphyrin Ligand” ACS Catal. 2013, 3, 1144-1148. 5. Lo, V. K.-Y.; Guo, Z.; Kwok, M. K.-W.; Yu, W.-Y.; Huang, J.-S.; Che, C.-M. “Highly Selective Intramolecular Carbene Insertion into Primary C–H Bond of -Diazoacetamides Mediated by a (p- Cymene)ruthenium(II) Carboxylate Complex” J. Am. Chem. Soc. 2012, 134, 7588–7591. 6. Che, C.-M.; Lo, V. K.-Y.; Zhou, C.-Y.; Huang, J.-S. “Selective Functionalisation of Saturated C–H Bonds with Metalloporphyrin Catalysts” Chem. Soc. Rev. 2011, 40, 1950–1975.

98 Iodonium Ylides Meet Blue Light: A Novel Synthesis of Activated Cyclopropanes Dr. Graham K. Murphy Department of Chemistry, University of Waterloo, Waterloo, Ontario, Canada, N2L3G1 [email protected]

Iodonium ylides are environmentally-benign surrogates for diazo compounds in the thermal, photochemical, or metal-catalyzed generation of (metallo)carbenes.1 As with diazocarbonyl compounds, their ensuing carbenes are highly effective in processes such as transylidation, cyclopropanation, C-H insertion and so on. There does exist significant differences in the reactivities of iodonium and diazonium ylides, which derives from their differences in ylide bonding. For example, the diazo derivative of Meldrum’s acid is largely inert to metal catalysis, whereas the corresponding iodonium ylide (1) readily undergoes decomposition under rhodium catalysis.2 Iodonium ylides will also undergo room temperature intramolecular cyclopropanations, whereas the analogous diazo compounds do not.3 These two ylides also differ in the photochemistry achievable upon blue light irradiation from LEDs. Irradiation of diazo compounds gives free carbene-type reactivity, but such processes are generally limited to donor/acceptor diazos, as neither -diazocarbonyls or -diazo--dicarbonyls absorb blue light photons.4 Conversely, - dicarbonyl-derived iodonium ylides do absorb blue light, opening avenues for investigating new LED- based photochemical reactions of -dicarbonyl substrates.

We discovered a facile and highly chemoselective synthesis of doubly activated cyclopropanes, that proceeds in yields up to 96%.5 This novel, metal-free reaction occurs when mixtures of alkenes and iodonium ylides are irradiated with light from blue LEDs, and it is operative with numerous ylides and electronically-diverse alkenes. Unlike the related diazo-based processes that involve free carbenes, computational analysis explains how, for iodonium ylides, the blue light drives a HOMO to LUMO excitation instead of bond cleavage. These reactions are proposed to instead proceed via biradical intermediate 2, where the bonds of cyclopropane 3 are forged within the ligand sphere of iodine. These results further support the notion that iodine, when in a hypervalent state, largely behaves as a late transition-metal.

Me Me Me Me Me Me blue LED O O OO lmax = 461 OO R - PhI O O O O R O O I I Ph Ph R R 1 2 3

References

(1) Yusubov, M. S.; Yoshimura, A.; Zhdankin, V. V., Arkivoc 2016, 1, 342. (2) Müller, P.; Allenbach, Y.; Robert, E., Tetrahedron: Asymmetry 2003, 14, 779. (3) Moriarty, R. M.; Tyagi, S.; Kinch, M., Tetrahedron 2010, 66, 5801. (4) For examples see: (a) Jurberg, I. D.; Davies, H. M. L., Chem. Sci. 2018, 9, 5112; (b) Hommelsheim, R.; Guo, Y.; Yang, Z.; Empel, C.; Koenigs, R. M., Angew. Chem., Int. Ed. 2019, 58, 1203; (c) Xiao, T.; Mei, M.; He, Y.; Zhou, L., Chem. Commun. 2018, 54, 8865; (d) Yang, J.; Wang, J.; Huang, H.; Qin, G.; Jiang, Y.; Xiao, T., Org. Lett. 2019, 21, 2654. (5) Chidley, T.; Jameel, I.; Rizwan, S.; Peixoto, P. A.; Pouységu, L.; Quideau, S.; Hopkins, W. S.; Murphy, G. K., Angew. Chem., Int. Ed. 2019, 58, 16959.

99

CURRICULUM VITAE – Graham K. Murphy

Associate Professor of Chemistry Department of Chemistry Department of Chemistry University of Waterloo Waterloo, Ontario, Canada, N2L3G1 University of Waterloo Waterloo, Canada, N2L3G1 Tel: 001 (519) 888-4567 x31735 Email: [email protected] Homepage: https://uwaterloo.ca/murphy-lab/

Scientific Vita JSPS PDF Tohoku University, Japan, 2006-2007 (M. Hirama) NSERC PDF Colorado State University, USA, 2008-2010 (J.L. Wood) PDF Biorefining and Conversions Network, University of Alberta, 2010-2011, (F.G. West)

Assistant Professor University of Waterloo, 2011-2017 Associate Professor University of Waterloo, 2017-

Research Field Synthetic methodology; reactivity mediated by hypervalent iodine reagents; materials synthesis for energy storage; fluorination and radiofluorination; fluorinative rearrangements

Selected Awards and Recognition 1. Outstanding Performance Award, UWaterloo (2019) 2. Province of Ontario Early Researcher Award (2016) 3. CNC-IUPAC Travel Award (2016) 4. Outstanding Performance Award, UWaterloo (2015) 5. Thieme Chemistry Journal Award (2014) 6. Natural Sciences and Engineering Research Council (NSERC) Postdoctoral Fellowship (2008-2010) 7. Japan Society for the Promotion of Science Postdoctoral Fellowship (2006-2007)

Representative Publications 1. Tristan Chidley, Islam Jameel, Shafa Rizwan, Philippe A. Peixoto, Dr. Laurent Pouységu, Dr. Stéphane Quideau,* Dr. W. Scott Hopkins* and Dr. Graham K. Murphy*, "Blue LED Irradiation of Iodonium Ylides Gives Diradical Intermediates for Efficient Metal-Free Cyclopropanation with Alkenes", Angew. Chem., Int. Ed. 2019, 58, 16959. 2. Tristan Chidley and Graham K. Murphy*, Cyclopropanation of Alkenes with Metallocarbenes Generated from Monocarbonyl Iodonium Ylides", Org. Biomol. Chem., 2018, 16, 8486. 3. Benjamin A. Laevens, Jason Tao and Graham K. Murphy*, " Iodide-Mediated Synthesis of Spirooxindolo Dihydrofurans from Iodonium Ylides and 3-Alkylidene-2-oxindoles" J. Org. Chem., 2017, 82, 11903. 4. Jason Tao, Carl D. Estrada and Graham K. Murphy*, "Metal-Free Intermolecular Cyclopropanation Between Alkenes and Iodonium Ylides Mediated By PhI(OAc)2•Bu4NI" Chem. Commum. 2017, 53, 9004.

100 CuI- and FeII-Catalyzed Insertion Reactions into the Si–H Bond

Thierry Ollevier

Department of Chemistry, Laval University Quebec City, G1V 0A6 (QC), Canada; E-mail: [email protected]

Metal catalysts are fundamental tools in synthetic organic chemistry. Copper and iron are very abundant elements; their low cost and environmentally benign character make them attractive to use in catalysis. We report their application in the metal-catalyzed insertion reactions of α-diazo compounds into Si–H bonds and demonstrate the scope and applicability of the reaction using highly practical conditions.1 We focused here on efficient and green metal catalytic systems to probe the reactivity of α-diazo compounds into Si–H bonds. An efficient copper-catalyzed carbenoid insertion reaction of α-diazo carbonyl compounds into Si–H and S–H bonds was 2 developed. The Fe(OTf)2-catalyzed carbene insertion reaction of α-diazo carbonyl compounds into the Si–H bond was also reported.3 An asymmetric Si−H insertion reaction of 1-aryl-2,2,2-trifluoro-1-diazoethanes leading to enantioenriched (1-aryl)-2,2,2-trifluoroethyl)silanes involved a simple CuI-catalyzed system comprising bis-((2,6-dichlorobenzylidene) di-imino)cyclohexane as the chiral ligand.4 The corresponding enantioenriched (1-aryl)- 2,2,2-trifluoroethyl)-silanes were obtained with excellent yields and enantioselectivities and the reaction was developed in dimethyl carbonate as a green solvent alternative.

References 1. For a review, see: Keipour, H.; Carreras, V.; Ollevier, T. Org. Biomol. Chem. 2017, 15, 5441–5456. 2. Keipour, H.; Jalba, A.; Delage-Laurin, L.; Ollevier, T. J. Org. Chem. 2017, 82, 3000–3010. 3. Keipour, H.; Ollevier, T. Org. Lett. 2017, 19, 5736–5739. 4. Carreras, V.; Besnard, C.; Gandon, V; Ollevier, T. Org. Lett. 2019, 21, 9094–9098.

101 CURRICULUM VITAE – Thierry Ollevier

Professor of Chemistry Department of Chemistry, Laval University Quebec City, G1V 0A6 (QC), Canada Tel.: +1 (418) 656-5034 E-mail: [email protected] Homepage: http://www2.chm.ulaval.ca/tollevier/

Scientific Vita Since 2010 Professor, Laval University 2006–2010 Associate Professor, Laval University 2001–2006 Assistant Professor, Laval University 2000–2001 Postdoctoral Fellow, University of Montréal 1998–2000 Postdoctoral Fellow, Stanford University 1997 Postdoctoral Fellow, Université catholique de Louvain, Belgium

Research Fields Synthetic methodology; asymmetric catalysis; metal carbene chemistry; reactions of diazo compounds; oxidation catalysis; Lewis acid catalysis

Awards and Recognition 2016 Fellow of the Royal Society of Chemistry–UK 2012 Best Young Presenter Prize of the Australian Journal of Chemistry (Eurasia12 meeting) 1997 Stas Prize from the Belgian Royal Academy

Representative Publications

1. Carreras, V.; Besnard, C.; Gandon, V; Ollevier, T. “Asymmetric CuI-Catalyzed Insertion Reaction of 1-Aryl-2,2,2-trifluoro-1-diazoethanes into Si–H Bonds” Org. Lett. 2019, 21, 9094–9098. 2. Li, M.; Carreras, V.; Jalba, A.; Ollevier, T. “Asymmetric Diels-Alder Reaction of α,β-Unsaturated Oxazolidin-2-one Derivatives Catalyzed by a Chiral Fe(III)-Bipyridine Diol Complex” Org. Lett. 2018, 20, 995–998. 3. Xu, W.; Ollevier, T.; Kleitz, F. “Iron-Modified Mesoporous Silica as Efficient Solid Lewis Acid Catalyst for the Mukaiyama Aldol Reaction” ACS Cat. 2018, 8, 1932–1944. 4. Keipour, H.; Ollevier, T. “Iron-Catalyzed Carbenoid Insertion of α-Diazoesters into Si–H Bonds” Org. Lett. 2017, 19, 5736–5739. 5. Kraïem, J.; Ollevier, T. “Atom economical synthesis of N-alkylbenzamides via iron(III) sulfate catalyzed rearrangement of 2-alkyl-3-aryloxaziridines in water and in the presence of surfactant” Green Chem. 2017, 19, 1263–1267. 6. Pichette Drapeau, M.; Fabre, I.; Grimaud, L.; Ciofini, I.; Ollevier, T.; Taillefer, M. “Transition-Metal-Free α-Arylation of Enolizable Aryl Ketones and Mechanistic Evidence for a Radical Process” Angew. Chem., Int. Ed. 2015, 54, 10587–10591.

102

Gold(I)-Catalyzed Divergent Carbene Cascade Reactions of Alkyne Tethered Diazo Compounds Ming Bao, Wenhao Hu∗, Xinfang Xu∗

Guangdong Provincial Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, 510275, China

Transition-metal-catalyzed carbene reactions of diazo compounds represent a powerful tool in modern organic synthesis, allowing for the rapid assembly of valuable complex molecules which cannot be readily synthesized by other method. As the continuation of our interest in the carbene/alkyne metathesis (CAM) transformations,1 recently, we have found that the use of appropriate protic additives could enable to regulation the reaction outcome by fine-tuning the catalytic selectivity of the gold(I) complex in the diazo-yne carbocyclization cascade reactions, which provides general access for the synthesis of furan and isomycin derivatives in good to high yields with broad substrate scope under mild reaction conditions via different processes.2 Then, a novel gold-catalyzed Wolff rearrangement/carbocyclization cascade reaction of alkyne tethered diazoketones has been developed, which provides a general access for the synthesis of indenes and benzo[d]oxepines in the presence of alcohols and indoles, respectively (Fig.1).

Fig. 1 Diazo-yne carbocyclization References: 1. For review: (a) Pei, C.; Zhang, C.; Qian, Y.; Xu, X. Org. Biomol. Chem. 2018, 16, 8677. Selected recent examples: (b) Dong, K.; Pei, C.; Zeng, Q.; Wei, H.; Doyle, M. P.; Xu, X. ACS Catal. 2018, 8, 9543. (c) Zheng, Y.; Bao, M.; Yao, R.; Qiu, L.; Xu, X. Chem. Commun. 2018, 54, 350. (d) Zhang, C.; Li, H.; Pei, C.; Qiu, L.; Hu, W.; Bao, X.; Xu, X. ACS Catal. 2019, 9, 2440. (e) Zheng, Y.; Mao, J.; Weng, Y.; Zhang, X.; Xu, X. Org. Lett. 2015, 17, 5638 (f) Yao, R.; Rong, G.; Yan, B.; Qiu, L.; Xu, X. ACS Catal. 2016, 6, 1024. (g) Wang, X.; Zhou, Y.; Qiu, L.; Yao, R.; Zheng, Y.; Zhang, C.; Bao, X.; Xu, X. Adv. Synth. Catal. 2016, 358, 1571. 2. (a) Bao, M.; Qian, Y.; Su, H.; Wu, B.; Qiu, L.; Hu, W.; Xu, X. Org. Lett. 2018, 20, 5332. (b) Bao, M.; Wang, X.; Qiu, L.; Hu, W.; Chan, P.; Xu, X. Org. Lett. 2019, 21, 1813.

* E-mail: [email protected]

103 Enantioselective Synthesis of Isochromans and Tetrahydroisoquinolines by C–H Insertion of Donor/Donor Carbenes

Benjamin D. Bergstrom, Jared T. Shaw Department of Chemistry, University of California – Davis, Davis, CA 95616, USA [email protected]

Asymmetric C–H insertion has been well-documented for acceptor, acceptor/acceptor, and donor/acceptor carbenes.1–4 Acceptor and acceptor/acceptor carbenes are very reactive and can react indiscriminately with other functionalities on the molecule, while donor/acceptor carbenes are less electrophilic due to the donating substituent, increasing selectivity for C–H insertion. Recently, we have been interested in donor/donor carbenes, which have reduced electrophilicity and are highly selective for C–H insertion while also tolerating many functional groups.5–7 Reports of C–H insertions forming six- membered rings containing heteroatoms are rare due to the kinetic favorability of five-membered ring insertions and the possibility of a Stevens rearrangement occurring after nucleophilic attack on the carbene by a heteroatom.8

6-Membered Ring Formation with Competitive Stevens Rearrangement Acceptor-Substituted Carbenes [Rh] X R2 X [Rh] 2 2 R2 R X R R R2 EWG EWG EWG EWG EWG EWG 2 R X desired 1,5-C-H insertion 1,6-C-H insertion EWG Hashimoto, 2015 kinetically favored desired [Rh]

Donor/Donor Carbenes -23 examples [M] [M] [M] R -single diastereomer Rh2( -PTAD)4 R2 X [Rh] (1 mol%) -up to >99.5:0.5 er 2 EDG EDG EDG EWG EWG EWG X R 0 ºC to rt -one-pot conditions EDG EDG -reduced carbene Carbene Electrophilicity electrophilicity, no Shaw, 2019 desired rearrangement Functional Group Tolerance

Using donor/donor carbenes and Rh2(R-PTAD)4 as a catalyst, we have synthesized a collection of isochroman substrates in good yield, with excellent diastereo- and enantioselectivity, and no rearrangement products were observed.9 Furthermore, we report the first synthesis of six-membered rings containing nitrogen by C–H insertion to form tetrahydroisoquinolines. In one case, a Stevens rearrangement product was isolated at elevated temperature from a carbamate-protected amine substrate and computational evidence suggests formation through a free ylide not bound to rhodium.

References: 1 G. A. Sulikowski, K. L. Cha and M. M. Sulikowski, Tetrahedron: Asymmetry, 1998, 9, 3145–3169. 2 M. P. Doyle, M. A. McKervey and T. Ye, in Modern Catalytic Methods for Organic Synthesis with Diazo Compounds: From Cyclopropanes to Ylides, Wiley, 1998, pp. 112–162. 3 H. M. L. Davies and R. E. J. Beckwith, Chem. Rev., 2003, 103, 2861–2904. 4 H. M. Davies and Ø. Loe, Synthesis, 2004, 16, 2595–2608. 5 C. Werlé, R. Goddard, P. Philipps, C. Farès and A. Fürstner, J. Am. Chem. Soc., 2016, 138, 3797–3805. 6 C. Soldi, K. N. Lamb, R. A. Squitieri, M. González-López, M. J. Di Maso and J. T. Shaw, J. Am. Chem. Soc., 2014, 136, 15142–15145. 7 L. W. Souza, R. A. Squitieri, C. A. Dimirjian, B. M. Hodur, L. A. Nickerson, C. N. Penrod, J. Cordova, J. C. Fettinger and J. T. Shaw, Angew. Chemie Int. Ed., 2018, 57, 15213–15216. 8 M. Ito, Y. Kondo, H. Nambu, M. Anada, K. Takeda and S. Hashimoto, Tetrahedron Lett., 2015, 56, 1397–1400. 9 L. A. Nickerson, B. D. Bergstrom, M. Gao, Y.-S. Shiue, C. J. Laconsay, M. R. Culberson, W. A. Knauss, J. C. Fettinger and J. T. Shaw, Chem. Sci., 2019, In press.

104 Tethered Axial Coordination as a Control Element on Dirhodium Paddlewheel Complexes

Ampofo Darko Department of Chemistry, University of Tennessee, Knoxville, Tennessee, 37996, USA [email protected]

Dirhodium paddlewheel complexes can mediate a number of transformations through the catalytic decomposition of diazo compounds. The reactivity and selectivity of these reactions are modulated partly by the modification bridging ligands surrounding the metal center. While general strategies for ligand design have largely involved modification of bridging ligands, additives in these reactions have also been observed to affect the reactivity and selectivity of the catalyst. It is speculated that coordination to the axial sites of the catalyst is responsible for the perturbations in catalyst performance. While there are current research efforts to probe the benefits of axial coordination, there is still need for robust methods to clarify their structural and electronic influence on catalyst reactivity and product selectivity. To adequately use axial coordination as a control element, we have designed paddlewheel complexes with tethered Lewis basic groups onto traditional bridging ligands. In initial studies, thioether ligands proved to be the most robust Lewis base when tethered to oxazolindinate or carboxylate bridging ligands. The novel complexes were then used in diazo-mediated cyclopropanation reactions, Si-H reactions, and C-H insertion reactions. The results of the experiments, along with spectroscopic and computational analyses, provided insight into the role that tethered axial coordination plays in diazo-mediated reactions.

[Rh] = (Ar)H CO2R’ O O R [Rh] R O O Ph O O or or Rh Rh S O O Ph X (Ar)H CO2R’ O O Rh Rh S R H RX H O O O O N2 HN O N (Ar)H CO2R’ O O X = Si, C

References 1. Sheffield, W.; Abshire, A.; Darko, A. “Effect of Tethered, Axial Thioether Coordination on Rhodium(II)-Catalyzed Silyl-Hydrogen Insertion.” European Journal of Organic Chemistry. 2019, 6347-6351. 2. Anderson, B. G.; Cressy, D.; Patel, J. J.; Harris, C. F.; Yap, G. P. A.; Berry, J. F.; Darko, A. “Synthesis and Catalytic Properties of Dirhodium Paddlewheel Complexes with Tethered, Axially Coordinating Thioether Ligands.” Inorganic Chemistry. 2019, 58, 1728-1732.

105 In-Situ Characterization of Reactive Metal–Nitrenoid Intermediates

Anuvab Das Department of Chemistry, Texas A&M University, College Station, Texas 77843, USA [email protected]

Metal-catalyzed nitrene-transfer catalysis has become an important technology for the construction of C–N bonds.1 In particular, the combination of transition metal catalysts with nitrene-transfer reagents, such as iminoiodinanes,2 organic azides,3 and hydroxylamine derivatives,4 to generate the reactive metal nitrenoid, have emerged as powerful methods to participate in C–H amination catalysis. However, the same reactivity that makes these species attractive towards catalysis also makes them challenging to isolate and characterize. Thus, information regarding these species is either obtained from computational investigations or by synthetically tuning the ligand environment to attenuate the reactivity, thus making them stable for characterization.5,6 Here, we report, a synthetic strategy to photogenerate reactive metal-nitrenoids, which was then utilized to spectroscopically characterize a Rh2–nitrenoid species by time-resolved UV-vis spectroscopy and variable laser MALDI-MS.7 We have also advanced photocrystallography, a technique that couples in situ crystallography with photochemistry, to structurally characterize these transient metal-nitrenoid species via single-crystal-to- single-crystal transformation.8

Figure 1. (a) Photolysis of the red-colored Rh2 N-chlorotosylamide complex resulted in the evolution of a new green-colored reduced Rh2 complex and aminated THF. (b) Structural characterization of a Rh2 nitrenoid via in-situ crystallography. Thermal ellipsoid plots are drawn at 50% probability with H atoms and solvent removed for clarity. Metrices for Rh2 adamantylazide complex — Rh(1)–Rh(1): 2.3968(8) Å, Rh(1)–N(1): 2.335(3) Å, N(1)–N(2): 1.254(5) Å, N(2)–N(3): 1.135(5) Å. Metrices for Rh2 nitrenoid intermediate — Rh(1)–Rh(1): 2.3903(4) Å, Rh(1)–N(1B): 2.12(2) Å, Rh(1)–N(1A): 2.346(4) Å.

References

1. Park, Y.; Kim, Y.; Chang, S. Chem. Rev. 2017, 117, 9247–9301. 2. Roizen, J. L.; Harvey, M. E.; Du Bois, J. Acc. Chem. Res. 2012, 45, 911–922. 3. Shin, K.; Chang, S. J. Org. Chem. 2014, 79, 12197–12204. 4. Barton, D. H. R.; Hay-Motherwell, R. S.; Motherwell, W. B. J. Chem. Soc., Perkin Trans. 1 1983, 445–451. 5. Varela-Alvarez, A.; Yang, T. H.; Jennings, H.; Kornecki, K. P.; Macmillan, S. N.; Lancaster, K. M.; Mack, J. B. C.; Du Bois, J.; Berry, J. F.; Musaev, D. G. J. Am. Chem. Soc. 2016, 138, 2327–2341. 6. Carsch, K. M.; DiMucci, I. M.; Iovan, D. A.; Li, A.; Zheng, S.-L.; Titus, C. J.; Lee, S. J.; Irwin, K. D.; Nordlund, D.; Lancaster, K. M.; Betley, T. A. Science 2019, 365, 1138–1143. 7. Das, A.; Maher, A. G.; Telser, J.; Powers, D. C. J. Am. Chem. Soc. 2018, 140, 10412–10415. 8. Das, A.; Chen, Y.-S.; Reibenspies, J. H.; Powers, D. C. J. Am. Chem. Soc. 2019, 141, 16232–16236.

106 The Role of Donor-Acceptor Cyclopropenes in Metal Carbene

Reactions. Conversion of E-Substituted Enoldiazoacetates to Z-

Substituted Metallo-Enolcarbenes

Kuiyong Dong

Department of Chemistry, University of Texas at San Antonio, San Antonio, Texas 78249, USA [email protected]

The influence of geometrical isomers of silyl-protected -substituted enoldiazoacetates has been examined in transition metal catalyzed vinylcarbene cycloaddition reactions. These reactions often occur with the intervention of donor-acceptor (D-A) cyclopropenes that can serve as metal carbene sources. Pathways to cycloaddition products that occur with and without D-A cyclopropene involvement have been identified. E--substituted enoldiazoacetates do not undergo cycloaddition reactions unless they first form D-A- cyclopropene intermediates. When cycloaddition reactions occur from the metallocarbene only after formation of the D-A cyclopropene, E--substituted enoldiazoacetates are converted to Z-γ-substituted metallo-enolcarbenes, and both geometrical isomers of silyl- protected -substituted enoldiazoacetates result in the same product selectivity.

References 1. Xu, X.; Doyle, M. P. “The [3+3]-Cycloaddition Alternative for Heterocycle Syntheses: Catalytically Generated Metalloenolcarbenes as Dipolar Adducts” Acc. Chem. Res. 2014, 47, 1396-1405. 2. Deng, Y.; Cheng, Q.-Q.; Doyle, M. P. “Asymmetric [3+3]-Cycloaddition for Heterocycle Synthesis” Synlett 2017, 1695-1706. 3. Dong, K.; Marichev, K. O.; Xu, X.; Doyle, M. P. “High Stereocontrol in the Preparation of Silyl-Protected γ-Substituted Enoldiazoacetates” Synlett 2019, 30, 1457-1461. 4. Dong, K.; Marichev, K. O.; Doyle, M. P. “The Role of Donor-Acceptor Cyclopropenes in Metal Carbene Reactions. Conversion of E-Substituted Enoldiazoacetates to Z- Substituted Metallo-Enolcarbenes” Organometal. 2019. 38,4043-4050.

107

A Safe and Straightforward Access to Nitrocyclopropane Carboxylates via Continuous Flow Synthesis of -Diazocarbonyl Compounds

Vanessa Kairouz Department of Chemistry, Université de Montréal, Montreal, Quebec, Canada [email protected]

In spite of the great potential of stabilized -diazocarbonyl reagents as metal carbenes precursors, their inherent shock sensitivity and potential explosivity make them difficult to handle on large scale and restricts their use in the industry. Although several safer procedures and reagent variation have been reported, there is a genuine interest to improve the synthesis and the practicability of those reagents in order to reconcile industry and the diazo chemistry. The continuous flow synthesis of by-product free solutions of α-diazo bearing two electron- withdrawing groups is described.1 The goal of the project was to develop a strategy for the sequential continuous -diazocarbonyl compounds generation using bench stable and safer reagents followed by metal-catalyzed cyclopropanation.

2 In order to achieve this goal, the strategy relies on using NfN3 as a stable diazo transfer agent, and on trapping NfNH2 and the base by-products affording a clean diazo stream at the outlet. The use of diethylamino ethyl polystyrene (PS-NEt2) in the form of a packed bed column was found to be very efficient to this purpose. Notably, this strategy allows a safe and straightforward access to shock-sensitive methyl 2-diazo-2-nitroacetate solution that can be directly used in the cyclopropanation of various styrenes in good to excellent yields in the presence of Rh2(OPiv)4. The in situ-generation of NfN3 was also achieved. This strategy allowed the diazo transfer to cyanoacetates and cyanoacetamides in good yields. The scope of the generation of clean diazo streams have been expanded using stronger supported bases such as polymer bound DBU which led to the diazomalanate formation in excellent conversion and no NfNH2 by-product were observed. Most importantly, it is possible to regenerate the packed bed columns following a simple reconditioning procedure. In fact, a dual column set-up allowed the uninterrupted continuous generation of by-products free diazo streams that were directly engaged in subsequent cyclopropanation reactions in conjunction with column recycling.

References 1. Muller, S. T. R.; Wirth, T. Diazo Compounds in Continuous-Flow Technology. ChemSusChem 2015, 8, 245-250. 2. Chiara, J. L.; Suarez, J. R. Synthesis of -Diazo Carbonyl Compounds with the Shelf-Stable Diazo Transfer Reagent NfN3. Adv. Synth. Catal. 2011, 353, 575-579.

108 Asymmetric Counteranion Catalyzed Enantioselective Multicomponent Reactions Based on Metal Carbene Zhenghui Kang, Dan Zhang, Xinfang Xu*, and Wenhao Hu*

School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China

Email: [email protected] Enantioselective multicomponent reactions (MCRs) via electrophilic trapping of ylide and zwitterionic active intermediates generated from metal carbene are highly efficient synthetic methods for the construction of complicated and functional group-enriched chiral molecules. However, the development of these new multicomponent reactions have been hindered as the substrate suitability and stereoselectivity control of these reactions are restricted due to the limitation of matching effective asymmetric catalytic strategies. Herein, by applying the ACDC concept, a series novel enantioselective aminomethylation reaction were disclosed, which via trapping the active nucleophilic intermediate based on metal carbene with the in situ generated tight ion pair of methylene iminium ion with corresponding chiral counteranion. Control experiments and DFT calculations indicate that the asymmetric induction was enabled by chiral anion via H-bonding and electrostatic interaction.

Reference

1. (a) Guo, X.; Hu, W.–H. Acc. Chem. Res. 2013, 46, 2427–2440. (b) Zhang, D; Hu, W.–H. Chem. Rec. 2017, 17, 739–753. 2. Kang, Z.; Wang, Y.; Zhang, D.; Wu, R.; Xu, X.; Hu, W. H. J. Am. Chem. Soc. 2019, 141, 1473–1478. 3. Kang, Z.; Zhang, D.; Xu, X.; Hu, W. H. Org. Lett. 2018, doi: 10.1021/acs.orglett.9b03787 4. Kang, Z.; Zhang, D.; Shou, J.; Hu, W. H. Org. Lett. 2018, 20, 983–986

109 Metal-Catalyzed Reaction of Terminal Alkynes and Diazonapthoquiones

Mitsuru Kitamura Department of Applied Chemistry, Kyushu Institute of Technology 1-1 Sensui-cho, Tobata-ku, Kitakyushu, 804-8550, Japan [email protected]

2-Diazonaphthalen-1-(2H)-ones (diazonaphthoquinones, DNQs) are unique -diazocarbonyl compounds that are commonly used as photoresists. DNQs are regarded as protected naphthol derivatives and are potentially good aromatic building block, especially for naphthol derivatives. Previously, we have developed an efficient regioselective method for the synthesis of DNQs from the corresponding naphthols via a diazo-transfer with 2-azido-1,3-dimethylimidazolinium chloride (ADMC).1 This approach allowed the regioselective synthesis of 2-diazonaphthalen-1- (2H)-ones from 1-naphthols through a reaction with ADMP. Additionally, we have subsequently been investigating a series of metal-catalyzed reactions using using DNQs.2 In this presentation, we report several metal-catalyzed reaction between terminal alkynes and DNQs. Although simple metal-catalyzed cross coupling between alkyne derivatives and DNQs is hard, we found that the Pd-catalyzed cross-coupling between (tert-butyldimethylsilyl)ethynyl stannane and DNQ could successfully proceed to afford alkynyl naphthol.3h Furthermore, we developed a method for the synthesis of naphtho[1,2-b]furans via a Pd-catalyzed reaction of DNQ and 3h terminal alkynes in the presence of CuI and i-Pr2NH (Eq. 1). This approach was then successfully applied to the synthesis of furomollugin. Interestingly, terminal propargyl alcohols react with DNQ in the presence of Rh2(OAc)4 to give the corresponding dihydrodioxins in good to high yields.3h

References 1. (a) Kitamura, M.; Tashiro, N.; Sakata, R.; Okauchi, T. Synlett 2010, 2503-2505. (b) Kitamura, M.; Sakata, R.; Tashiro, N.; Ikegami, A.; Okauchi, T. Bull. Chem. Soc. Jpn. 2015, 88, 824-833. 2. For a review, see: Othman, D. I. A.; Kitamura, M. Heterocycles 2016, 92, 1761-1783. 3. For selected examples: (a) Kitamura, M.; Sakata, R.; Okauchi, T. Tetrahedron Lett. 2011, 52, 1931-1933. (b) Kitamura, M.; Kisanuki, M.; Okauchi, T.; Eur. J. Org. Chem. 2012, 905-907. (c) Kitamura, M.; Araki, K.; Matsuzaki, H.; Okauchi, T. Eur. J. Org. Chem. 2013, 5045-5049. (d) Kitamura, M.; Kisanuki, M.; Kanemura, K.; Okauchi T. Org. Lett. 2014, 16, 1554-1557. (e) Kitamura, M.; Takahashi, S.; Okauchi, T. J. Org. Chem. 2015, 80, 8406-8416. (f) Kitamura, M.; Otsuka, K.; Takahashi, S.; Okauchi, T. Tetrahedron Lett. 2017, 58, 3508–3511. (g) Othman, D. I. A.; Otsuka, K.; Takahashi, S.; Selim, K. B.; El-Sayed, M. A.; Tantawy, A. S.; Okauchi, T.; Kitamura, M. Synlett 2018 29, 457-462. (h) Takahashi, S., Shimooka, H., Okauchi, T., Kitamura, M. Chem. Lett. 2019, 48, 28-31.

110 Chiral Guanidines Promoted Enantioselective X-H Insertion Reactions of α-Diazoesters

Xiaohua Liu College of Chemistry, Sichuan University, Chengdu 610064, China [email protected]

As attractive organic superbases along with H-bonding ability of the corresponding salts, guanidine-containing chiral molecules have been synthesized and investigated as a new type of useful organocatalysts to promote a number of asymmetric reactions.1 Our group designed and synthesized a type of chiral guanidine-amide compounds which are characterized by an open-chain CN3 structure and the combination of readily modified amide units. The encounter of a guanidine base with the additional hydrogen-bonding donor amide functionalities at the same molecule enable us to carry out bifunctional asymmetric organocatalysis.2 Inspired by the hydrogen-attract and transfer ability of guanidine, we utilized chiral guanidine/Rh(II) cooperative catalytic strategy to the enantioselective carbene insertion into O-H bond of carboxylic acid3 and N-H bond of benzophenone imine. Moreover, inspired by σ-bond donating characteristics of guanidine moiety and potential coordination properties of amides unit, we also made a breakthrough on the application of chiral guanidine metal complex as a promotor in the asymmetric C-H insertion reaction of α-diazoesters with terminal alkynes4,5 and azide-alkyne cycloaddition/[2+2] cascade reaction.6

References 1. Dong, S. X.; Feng, X. M.; Liu, X. H. “Chiral Guanidines and Their Derivatives in Asymmetric Synthesis” Chem. Soc. Rev. 2018, 47, 8525–8540. 2. Kang, T. F.; Zhao, P.; Yang, J.; Lin, L. L. Feng, X. M.; Liu, X. H. “Asymmetric Catalytic Double Michael Additions for the Synthesis of Spirooxindoles” Chem. Eur. J. 2018, 24, 3703–3706. 3. Tan, F.; Liu, X. H.; Hao, X. Y.; Tang, Y.; Lin, L. L.; Feng, X. M. “Catalytic Insertion of α-Diazo Carbonyl Compounds into O−H Bonds of Carboxylic Acids” ACS Catal. 2016, 6, 6930−6934. 4. Tang, Y.; Chen, Q. G.; Liu, X. H.; Wang, G.; Lin, L. L.; Feng, X. M. “Direct Synthesis of Chiral Allenoates from the Asymmetric C-H Insertion of α-Diazoesters into Terminal Alkynes” Angew. Chem. Int. Ed. 2015, 54, 9512. 5. Tang, Y.; Xu, J.; Yang, J.; Lin, L. L.; Feng, X. M.; Liu, X. H. “Asymmetric Three-Component Reaction for the Synthesis of Tetrasubstituted Allenoates via Allenoate-Copper Intermediates” Chem 2018, 4, 1658–1672. 6. Guo, S. S.; Dong, P.; Chen, Y. S.; Feng, X. M.; Liu, X. H. “Chiral Guanidine/Copper Catalyzed Asymmetric Azide-Alkyne Cycloaddition/[2+2] Cascade Reaction” Angew. Chem. Int. Ed. 2018, 57, 16852–16856.

111 Chiral Donor-Acceptor Azetines for Synthesis of Azetidines and Functionalization of Nucleophiles

Kostiantyn O. Marichev and Michael P. Doyle

Department of Chemistry, University of Texas at San Antonio, San Antonio, Texas 78249, USA [email protected]

Our research group developed broad applications of [3+3]- and [3+2]-cycloaddition reactions of enoldiazo compounds.1 This work is focused on the development of a [3+1]-cycloaddition reaction that allows the introduction of a heteroatom to the four-membered ring. We demonstrated that donor-acceptor azetines (donor = silyloxy group, acceptor = carboxylate group) could be formed in up to 95% isolated yield and 99% ee, and that these azetines could be conveniently converted to all-cis substituted azetidines via catalytic hydrogenation.2 We envisioned that removal of the silyl group from the azetine product would form 3-azetidinones that would be susceptible to retro-Claisen ring opening because of the high ring strain in the four-membered ring. We report that this reaction provides a general methodology for the attachment of chiral units to a variety of amines and alcohols, and tolerates a broad scope of nucleophiles, including naturally occurring amines, alcohols, amino acids, and other nitrogen- based nucleophiles.3 Recent studies have shown that these reactions can be performed in aqueous media with the use of only one equivalent of nucleophile. In addition, the mild reaction conditions, high enantiocontrol, and broad scope demonstrated in this work portray a process that is expected to have wide applications.

References

1. Cheng, Q.-Q., Deng, Y., Lankelma, M. & Doyle, M. P. “Cycloaddition reactions of enoldiazo compounds” Chem. Soc. Rev. 46, 5425–5443 (2017). 2. Marichev, K. O. et al. Synthesis of chiral tetrasubstituted azetidines from donor-acceptor azetines via asymmetric copper(I)-catalyzed imido-ylide [3+1]-cycloaddition with metallo-enolcarbenes. Angew. Chem. Int. Ed. 58, 16188–16192 (2019). 3. Marichev, K. O. et al. Chiral donor-acceptor azetines as powerful reactants for synthesis of amino acid derivatives. Nat. Commun. 10, 5328 (2019).

112 Visible Light Induced Allene Formation Through Doyle-Kirmse Reaction

Katarzyna Orłowskaa), Katarzyna Rybicka-Jasińskaa), Dorota Grykoa)* a)Institute of Organic Chemistry, Polish Academy of Sciences, M. Kasprzaka 44/52 01-224 Warsaw, Poland, [email protected], [email protected]

Diazo compounds as a source of reactive species are considered a powerful tool in organic synthesis. Upon photolysis, thermolysis, or metal catalysis they generate carbenes in either singlet or triplet state, which then easily undergo rearrangements, insertion reactions, cycloadditions, and others.1 Application of visible light in organic transformations, since these processes are more environmental-friendly, is of growing interest. In this line, both elimination of expensive and toxic metal catalysts and application of visible light, make such methods extremely attractive. Photochemical reactions engaging diazo compounds have been investigated over the years.2 Although UV-light-induced carbene generation is well known in diazo chemistry, only recently it became clear that introduction of a donor group to diazoacetates shifts the absorption spectra batochromically enabling their photolysis under blue irradiation.3 α-Diazoesters have been also utilized in visible light mediated photoredox reactions. They were distinguished as efficient alkylating reagents of carbonyl compounds4,5 and 2-acylimidazoles which in the presence of chiral photocatalysts furnish products with high enanioselectivities.6 Recently, Xiao and coworkers proposed blue-light mediated, metal-free gem-difluoroallylation of aryl diazoesters.7 Despite growing interest in diazo chemistry, still little is known about reactivity of these compounds upon light irradiation. Here, we present light induced approach toward allene synthesis (Scheme 1). The plausible mechanism involves carbene and subsequent ylide formation in the presence of propargil reagent followed by [2,3] rearrangement to give desired allene product. The methodology leads to an efficient functionalization of methylenes in a fast and green way with extrusion of nitrogen as a side product.

References 1. Ford, A.; Miel, H.; Ring, A.; Slattery, C. N.; Maquire, A. R.; McKervey, M. A. “Modern Organic Synthesis with α-Diazocarbonyl Compounds” Chem Rev. 2015, 115, 9981-10080. 2. Ciszewski, Ł. W.; Rybicka-Jasińska, K.; Gryko, D. “Recent developments in photochemical reactions of diazo compounds” Org. Biomol. Chem. 2019, 17, 432-448. 3. Jurberg, I. D.; Davies, H. M. L. “Blue light-promoted photolysis of aryldiazoacetates” Chem. Sci. 2018, 9, 5112-5118. 4. Rybicka-Jasińska, K.; Shan, W.; Zawada, K.; Kadish, K. M.; Gryko D. “Porphyrins as Photoredox Catalysts: Experimental and Theoretical Studies” J. Am. Chem. Soc. 2016, 138, 15451-15458. 5. Rybicka-Jasińska, K.; Orłowska, K; Karczewski, M; Zawada, K; Gryko, D. “Why Cyclopropanation is not Involved in Photoinduced α-Alkylation of Ketones with Diazo Compounds” Eur. J. Chem. 2018, 47, 6634-6642. 6. Huang, X.; Webster, R. D.; Harms, K.; Meggers, E. “Asymmetric Catalysis with Organic Azides and Diazo Compounds Initiated by Photoinduced Electron Transfer” J. Am. Chem. Soc. 2016, 138, 12636- 12642. 7. Yang, J.; Wang, J.; Huang, H.; Qin, G.; Jiang, Y.; Xiao, T. “gem-Difluoroallylation of Aryl Diazoesters via Catalyst-Free, Blue-Light-Mediated Formal Doyle-Kirmse Reaction” Org. Lett. 2019, 21, 2654-2657.

113 Progress Toward the Synthesis of Brazilide A Davis Plasko 2/5-7/2020 Advisor: Dr. Jeremy May Brazilide A was isolated from Sappan Lignum, the heartwood of Caesalpinia sappan L., which is used in traditional Chinese medicine. Only one total synthesis of brazilide A has been published due to the complexity of the propellane core. However, the May lab has developed a method for the concise synthesis of this propellane core. A carbene/alkyne cascade reaction on the diazoester 1, terminating in C−H bond insertion, can form functionalized bridged tricycle 2 and can be followed by a base-catalyzed rearrangement to form the propellane core 3 as depicted in Scheme 1. From this core, the synthesis of brazilide A is being developed.

Scheme 1: Carbene/alkyne cascade and base-promoted rearrangement

114

Bio-inspired Multiple Catalytic Systems Design and Their Applications in Organic Synthesis

Huang Qiu*, Sifan Yu, Wenhao Hu* Guangdong Key Laboratory of Chiral Molecule and Drug Discovery and School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China. e-mail: [email protected]; [email protected] Nature has evolved a highly efficient synthetic platform for assembling complex biomolecules from simple precursors, and high-performance enzymes as well as multiple catalytic systems are considered to be essential for this platform.1 As a result, great progress has been achieved in the development of bioinspired catalysts for diverse valuable transformations over the past several decades. In contrast, construction of multiple catalytic systems inspired by nature’s biosynthesis remains a more challenging task, probably due to various compatibility and selectivity issues. Meanwhile, multicomponent reactions (MCRs) have shown much higher atom and step economy in constructing complex molecules, and the development of novel higher-order MCRs and realization of asymmetric multicomponent reactions (AMCRs) have emerged as the frontiers in chemistry because of their great synthetic values.2 Here, we design a triple catalytic cycle that enables a novel highly diastereoselective and enantioselective four-component reaction based on our previous report.3 This reaction proceeds under mild reaction conditions and shows high functional group tolerance as well as broad substrate scope, affording the desired four-component coupling products (> 70 examples) with high efficiency and good to excellent stereocontrol.

Fig.1 A multiple catalysis-enabled enantioselective higher-order multicomponent reaction.

Reference:

1) Shi, J.; Wu, Y.; Zhang, S.; Tian, Y.; Yang, D. & Jiang, Z. Bioinspired construction of multi-enzyme catalytic systems. Chem. Soc. Rev., 2018, 47, 4295–4313.

2) Brauch, S.; Berkela, S. S. V. & Westermann, B. Higher-order multicomponent reactions: beyond four reactants. Chem. Soc. Rev., 2013, 42, 4948–4962.

3) Zhang, D.; Zhou, J.; Xia, F.; Kang, Z.; Hu, W. Bond cleavage, fragment modification and reassembly in enantioselective three-component reactions. Nat. Commun. 2015, 6, 5801.

115 Functionalization of alkenes with diazo compounds bypassing cyclopropane

Yongliang Su, Geng-Xin Liu, Jun-Wen Liu, Linh Tram, Huang Qiu, Michael P. Doyle Department of Chemistry, University of Texas at San Antonio, San Antonio, Texas 78249, USA [email protected]

The cyclopropanation of alkenes with diazo compounds is a well-known reaction whose cyclopropane products, are widely used as versatile three-carbon synthons for the synthesis of natural products, biologically active compounds, and pharmaceuticals. Although straightforward and widely used, conventional cyclopropane formation/cyclopropane ring-opening is a multi-step process that is thermodynamically inefficient and subject to the limitations of its constituent reactions, and we suggest that a cyclopropane-free strategy would be an attractive alternative.

We report here two complementary protocols with diazo compounds as the precursor of carbon radical achieving different functionalization of diverse alkenes. The diazo compound is transformed to a carbon radical with photocatalyst or iron catalyst through PCET process, which selectively adds to diverse alkenes delivering new carbon radical species that forms the hydroalkylation product through thio-catalyzed HAT process, or forms the azidoalkylation product through an iron catalyzed cycle. These two protocols occur under mild and operationally simple reaction conditions and show high functional group tolerance. Their broad substrate scope and subsequent diverse transformations, such as the synthesis of γ-amino esters and alcohols, as well as [5,5]-, [5,6]-, and [5,7]-spirolactam formation, show their high synthetic utility.

References 1. Ebner, C.; Carreira, E. M. “Cyclopropanation Strategies in Recent Total Syntheses” Chem. Rev. 2017 117, 11651-11679. 2. Cavitt, M. A.; Phun, L. H.; France, S. “Intramolecular donor–acceptor cyclopropane ring- opening cyclizations” Chem. Soc. Rev. 2014, 43, 804-818.

116 Spectroscopic Characterization of Manganese Porphyrin Nitrene Complexes Gerard Van Trieste Department of Chemistry, Texas A&M University, College Satation, Texas, 77843, USA [email protected] Metal–nitrenoid (M–NR) complexes are important moieties in synthetic chemistry, as they are often proposed as intermediates in C–H bond amination and olefin aziridination. Metalloporphyrin complexes featuring mid-to-late transition metals such as Mn, Fe and Co are ubiquitous in nitrene-mediated amination catalysis.1 To improve and develop new catalysts for chemical transformations, understanding the structure of these M–NR intermediates is critical. However, the exquisite reactivity of the M–NR species which renders them attractive to catalysis also results in their kinetic instability as characterization of these species is challenging under synthetic conditions. Thus, computational methods are relied on to obtain information. However, photochemical access to M–NR intermediates can facilitate spectroscopic measurements under cryogenic or time-resolved conditions. Recently, our group has developed photochemical precursors of M– NR species and characterized the photogenerated reactive M–NR compounds including Rh2 nitrenes and a Co iminyl radical.2-4 Here, we present the development Mn porphyrin photoprecursors to directly characterize reactive Mn–NR complexes in the solution phase.

Figure 1. Left: Thermal ellipsoid plots of a Mn porpyrin with an apical N-haloamine ligand which functions as a photoprecursor for reactive Mn–NR fragments. Hydrogen atoms and solvent molecules have been omitted for clarity. Ellipsoids drawn at 50% probability. Right: Photolysis of a Mn-haloamine complex which is hypothesized to generate a putative nitrenoid, which was monitored by UV-vis spectroscopy. References:

1. Singh, R.; Mukherjee, A. Metalloporphyrin Catalyzed C–H Amination. ACS Catal. 2019, 9, 3604–3617. 2. Das, A.; Maher, A. G.; Telser, J.; Powers, D. C. Observation of a Photogenerated Rh2 Nitrenoid Intermediate in C−H Amination. J. Am. Chem. Soc. 2018, 140, 10412–10415. 3. Das, A.; Chen, Y.-S.; Reibenspies, J. H.; Powers, D. C. Characterization of a Reactive Rh2 Nitrenoid by Crystalline Matrix Isolation. J. Am. Chem. Soc. 2019, 141, 16232–16236. 4. Baek, Y.; Das, A.; Zheng, S. -L.; Powers, D. C.; Betley, T. A. C–H Amination Mediated by Cobalt Organoazide Adducts and the Corresponding Cobalt Nitrenoid Intermediates. submitted.

117 Synthesis of Bridged Tricycles and Propellanes via Nitrene/Alkyne Cascades.

Qinxuan Wang and Jeremy A. May*

Department of Chemistry, University of Houston, 3585 Cullen Blvd, Fleming Bldg. Room 112, Houston, Texas 77204-5003, United States

A nitrene/alkyne cascade reaction terminating in C−H bond insertion to form functionalized bridged tricycles is presented. Propellanes can be obtained from bridged tricycles in an acid-promoted rearrangement. Different nitrene precursors were assessed, and carbonazidate was found to be the most productive. The relative reaction rates of nitrene/alkyne metathesis and direct nitrene C−H insertion were compared. Adding functional groups in the 3 position in the ring not only facilitate the substrate syntheses but also promote the terminal C−H insertion for the formation of bridged tricycles. Substrates with different ring sizes, different aryl groups and heteroaryl were also explored. Accordingly, 7-membered rings were the maximum ring size to be formed by nitrene/alkyne metathesis.

References 1. Jansone-Popova, S.; May, J. A. Synthesis of Bridged Polycyclic Ring Systems via Carbene Cascades Terminating in C−H Bond Insertion. J. Am. Chem. Soc. 2012, 134, 17877−17880. 2. Le, P. Q.; May, J. A. Hydrazone-Initiated Carbene/Alkyne Cascades to Form Polycyclic Products: Ring-Fused Cyclopropenes as Mechanistic Intermediates. J. Am. Chem. Soc. 2015, 137, 12219−12222. 3. Shih, J.-L.; Jansone-Popova, S.; Huynh, C.; May, J. A. Synthesis of Azasilacyclopentenes and Silanols via Huisgen Cycloaddition-Initiated C–H bond Insertion Cascades. Chem. Sci. 2017, 8, 7132−7137.

118 Chiral 3-Acylglutaric Acid Derivatives from Strain-induced Catalyst-free Nucleophilic retro-Claisen Ring-opening Reactions

Rui Wang, Michael P. Doyle Department of Chemistry, University of Texas at San Antonio, San Antonio, Texas 78249, USA [email protected]

Ring strain propels chemical reactions and is a well-recognized transformational strategy in chemistry and biology.1 Three-membered-ring epoxides and aziridines are notable candidates for their diverse uses and applications. By contrast, ring opening reactions of the cyclobutane ring, which would complement those of donor-acceptor cyclopropanes, have received far less attention. We have previously reported highly stereoselective [3+1]-cycloaddition of enoldiazoacetates to form donor-acceptor cyclobutene products that are precursors to β- ketoesters.2 We envisioned that their ring strain would favor nucleophilic ring opening (the retro- Claisen reaction).

We have previously reported this ring-opening process with the corresponding 2-azetines-2- carboxylates,3 but the same reaction conditions were unsuitable for retro-Claisen reactions of the more stable donor-acceptor cyclobutenes, and the reported 2-azetine ring opening required the use of two equivalents of nucleophile. We now report the ring-opening reactions of silyl-group protected donor-acceptor cyclobutenes with only one equivalent of nucleophile through the assistance of water to remove the silyl group. Various amines, alcohols and mercaptans are effective nucleophiles, and the optical purity of the reactant donor-acceptor cyclobutenes is fully retained in the 3-acylglutaric acid products that are further converted to valuable structures, including triols, GABA derivatives, and heterocycles.

References 1. (a) Kamath, A.; Ojima, I. “Advances in the Chemistry of Beta-lactam and Its Medicinal Applications” Tetrahedron 2012, 68, 10640. (b) Cavitt, M. A.; Phun, L. H.; France, S. “Intramolecular Donor-acceptor Cyclopropane Ring-opening Cyclizations” Chem. Soc. Rev. 2014, 43, 804. 2. Deng, Y.; Massey, L. A.; Zavalij, P.; Doyle, M. P. “Catalytic Asymmetric [3+1]- Cycloaddition Reaction of Ylides with Electrophilic Metallo-enolcarbene Intermediates” Angew. Chem. Int. Ed. 2017, 56, 7479. 3. Marichev, K. O.; Dong, K.; Massey, L. A.; Deng, Y.; Angelis, L. D.; Wang, K.; Arman, H.; Doyle, M. P. “Chiral Donor−acceptor Azetines as Powerful Reactants for Synthesis of Amino Acid Derivatives” Nat. Commun. 2019, 10, 5328.

119 Transition Metal-Catalyzed Transformations of N-Tosylhydrazones

Wanqing Wu Key Laboratory of Functional Molecular Engineering of Guangdong Province, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640, P. R. China [email protected]

N-Tosylhydrazones, derived easily from the corresponding ketones, are readily available and versatile synthons in organic synthetic chemistry. It is well known that N-tosylhydrazones can generate diazo compounds in situ in the presence of base and form the metal-carbene species, which are further applied in different organic transformations. Based on our continuing interest in the transition metal-catalyzed reactions, we recently have developed a series of novel methods employing N-tosylhydrazones as substrates, including cyclization reaction, cross-coupling reaction, difunctionalization and multi-component reaction under the copper or palladium catalytic systems. Various reaction patterns offered convenient access to diverse molecular skeletons with high efficiency, excellent selectivity, and step-economy, such as polysubstituted furans/pyrroles, α-arylnitriles, α-arylthioalkanenitriles, benzothiazoles, benzofurans, and dihydrobenzofurans. These new developed methods also provide more potential for further exploration of this powerful synthon.

References 1. Huang, Y.; Li, X.; Yu, Y.; Zhu, C.; Wu, W.; Jiang, H. “Copper-Mediated [3+2] Oxidative Cyclization Reaction of N-Tosylhydrazones and β-Ketoesters: Synthesis of 2,3,5- Trisubstituted Furans” J. Org. Chem. 2016, 81, 5014-5020. 2. Huang, Y.; Li, X.; Wang, X.; Yu, Y.; Zheng, J.; Wu, W.; Jiang, H. “Copper-catalyzed cyanothiolation to incorporate a sulfur-substituted quaternary carbon center” Chem. Sci. 2017, 8, 7047-7051. 3. Peng, J.; Gao, Y.; Zhu, C.; Liu, B.; Gao, Y.; Hu, M.; Wu, W.; Jiang. H. “Synthesis of Polysubstituted 3-Amino Pyrroles via Palladium-Catalyzed Multicomponent Reaction” J. Org. Chem. 2017, 82, 3581-3588. 4. Huang, Y.; Zhou, P.; Wu, W.; Jiang, H.; “Selective Construction of 2-Substituted Benzothiazoles from o-Iodoaniline Derivatives S8 and N-Tosylhydrazones” J. Org. Chem. 2018, 83, 2460-2466.

120 Catalytic Desymmetric Cycloaddition of Diaziridines with Metalloenolcarbenes: the Role of Donor-Acceptor Cyclopropenes

Haifeng Zheng, Michael P. Doyle Department of Chemistry, University of Texas at San Antonio, San Antonio, Texas 78249, USA [email protected]

The chiral nitrogenous bridged skeleton (Figure 1) occurs frequently in natural products and bioactive compounds.1 The development of asymmetric catalytic methods to access these structures is significant for natural product synthesis and for testing their bioactivity.

Figure 1. Nitrogenous bridged skeleton in natural products.

We report here the highly stereoselective formal [3+3] desymmetrization cycloaddition of diaziridines with enoldiazo compounds that occurs via nitrogen ylide formation followed by a novel N-N bond cleavage. Using a chiral copper(I)/Box catalyst, high enantioselectivities were obtained with -substituted enoldiazoacetates, and even higher enantiocontrol (up to 97% ee) was achieved with their derivative donor-acceptor cyclopropenes that produced only Z- metalloenolcarbene isomers as intermediates.2 The search for a chiral ligand that generated the highest enantioselectivity identified L10 as optimum. With this method a broad spectrum of highly enantioenriched bridged bis-nitrogen heterocyclic compounds were obtained in excellent yields and high diastereo- and enantio-selectivities.

References 1. Kobayashi, J.; Kubota, T. “the Daphniphyllum Alkaloids” Nat. Prod. Rep. 2009, 26, 936- 962. 2. Zheng, H. F.; Doyle, M. P. “Catalytic Desymmetric Cycloaddition of Diaziridines with Metalloenolcarbenes: The Role of Donor-Acceptor Cyclopropenes” Angew. Chem. Int. Ed. 2019, 58, 12502-12506.

121 Halogen-Bond-Promoted 1,3-Addition of Perfluoroalkyl Iodides to Alkenyldiazoacetates

Lei Zhou School of Chemistry, Sun Yat-sen University, Guangzhou, 510275, China [email protected]

Alkenyldiazoacetates have a rich and varied reactivity due to the presence of two valuable conjugated functional groups (alkene and diazo group) in their structure.1 A number of powerful synthetic methods have been developed based on these versatile reagents, especial their use as three-carbon building blocks to access various carbo- or heterocyclic frameworks through metal- catalyzed [3C+n] cycloadditions (n=1–5).2 Most of methods rely on the initial formation of electrophilic metal carbene intermediates through a diazo decomposition. By contrast, the development of new reactions triggered by their alkene motif is still challenging because many of the alkenyldiazoacetates are prone to 1,5-electrocyclization to form pyrazoles if diazo functionality cannot be decomposed rapidly. This limitation also restricts the use of alkenyldiazoacetates in a radical reaction despite they can be considered as a special type of alkenes.3

In this report, alkenyldiazoacetates were first developed as the radical acceptors in a ATRA reaction of RfI to give 1,3-difunctional adducts. The formation of halogen-bonded complexes between closed-shell singlet carbenes and perfluoroalkyl iodides followed by homolytic dissociation of C-I bond produces Rf radical, which enables initiation of a radical chain process without external photocatalysts and additives. After post-reaction isomerization, various 1-iodo- 3-perfluoroalkyl-alkenes were obtained in good yields with high Z-selectivity. The synthetic utility of the ATRA 1,3-adducts was demonstrated by cross-coupling reactions and defluorination of perfluoroalkyl groups.

References 1. (a) López, E.; González-Pelayo, S.; López, L. A. Recent developments in coinage metal catalyzed transformations of stabilized vinyldiazo compounds: beyond carbenic pathways. Chem. Rec. 2017, 17, 312−315. (b) Cheng, Q.-Q.; Yu, Y.; Yedoyan, J.; Doyle, M. P. Vinyldiazo reagents and metal catalysts: a versatile toolkit for heterocycle and carbocycle construction. ChemCatChem. 2018, 7, 488−496. 2. (a) Xu, X.; Doyle, M. P. The [3+3]-cycloaddition alternative for heterocycle syntheses: catalytically generated metalloenolcarbenes as dipolar adducts. Acc. Chem. Res. 2014, 47, 1396−1405. (b) Deng, Y.; Chen, Q.-Q.; Doyle, M. P. Asymmetric [3+3] cycloaddition for heterocycle synthesis. Synlett. 2017, 28, 1695−1706. (c) Cheng, Q.-Q.; Deng, Y.; Lankelma M.; Doyle, M. P. Cycloaddition reactions of enoldiazo compounds. Chem. Soc. Rev. 2017, 46, 5425–5443. (d) Yin, Z.; He, Y.; Chiu, P. Application of (4+3) cycloaddition strategies in the synthesis of natural products. Chem. Soc. Rev. 2018, 47, 8881−8924. (e) Marichev, K. O.; Doyle, M. P. Catalytic asymmetric cycloaddition reactions of enoldiazo compounds. Org. Biomol. Chem. 2019, 17, 4183−4195. 3. Sarabia, F. J.; Li, Q.; Ferreira, E. M. Cyclopentene annulations of alkene radical cations with vinyl diazo species using photocatalysis. Angew. Chem. Int. Ed. 2018, 57, 11015−11019.

122 Carbene-Transfer Reactions with Alkynes as Precursors

Shifa Zhu

Key Laboratory of Functional Molecular Engineering of Guangdong Province, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640, China Email: [email protected]

In the past decades, few intermediates have attracted as much interest as carbenes. Transition- metal carbene can be typically classified into five types: acceptor-carbene, acceptor/acceptor- carbene, donor/acceptor-carbene, donor-carbene and donor/donor-carbene according to the substituents attached to carbene carbon atom. Traditionally, diazo compounds are used as carbene precursors, especially for acceptor-, donor/acceptor-, and acceptor/acceptor-carbenes. However, few examples have been reported for donor-carbene and donor/donor-carbene through diazo approach due to the instability and potential explosiveness of the diazo compounds. These disadvantages severely limited the further applications of donor-carbene and donor/donor- carbene through the traditional diazo approaches. In recent years, alkynes were found to serve as safe and practical carbene source, which provided a new strategy to generate carbene intermediate in an efficient way, especially for the formation of donor- and donor/donor-carbene.[1] Our group have been making continuous efforts to develop safe and practical carbene chemistry based on alkyne chemistry.[2] Such a strategy would be particularly useful for donor- and donor/donor-carbenes because it is safe (no gas emission), practical (no slow addition required), and highly atom-efficient (up to 100% atom efficiency). In addition, the high reactivity, good selectivity, excellent functional-group tolerance, and mild reaction conditions also renders this strategy a feasible route for carbene transfer reactions.

References

[1] L. Chen, K. Chen, S. Zhu, Chem 2018, 4, 1208. [2] a) J. Ma, H. Jiang, S. Zhu, Org. Lett. 2014, 16, 4472; b) J. Ma, K. Chen, H. Fu, L. Zhang, W. Wu, H. Jiang, S. Zhu, Org. Lett. 2016, 18, 1322; c) D. Zhu, J. Ma, K. Luo, H. Fu, L. Zhang, S. Zhu, Angew. Chem., Int. Ed. 2016, 55, 8452; d) H. Luo, K. Chen, H. Jiang, S. Zhu. Org. Lett. 2016, 18, 5208; e) T. Cao, K. Chen, S. Zhu. Org. Chem. Front. 2017, 4, 450; f) D. Zhu, L. Chen, H. Zhang, Z. Ma, Jiang, H, S. Zhu, Angew.Chem., Int. Ed. 2018, 57, 12405. 123 N-heterocyclic carbene catalyzed atroposelective arene formation

Ting-Shun Zhu School of Chemistry, Sun Yat-Sen University, Guangzhou 510275, China [email protected]

Atropisomeric arenes are important structure in nature products, drug molecules, catalysts, and other functional molecules. The synthetic methods of these compounds are normally relied on asymmetric modification of pre-exist arenes, such as metal catalyzed cross coupling, aromatic electrophilic substitution (Ar-SE), point-to-axial chirality transfer, desymmetrization substitution, kinetic resolution etc. In comparison, asymmetric de novo construction of arenes is much less studied.1 Conventionally, transition-metal-catalyzed asymmetric [2+2+2] cycloaddition2 is almost the only method to achieve atropselective arene formation.

Herein we report a new atropselective arene formation method via N-heterocylic-carben organocatalyzed formal [4+2] cycloaddition.3 To the best of our knowledge, this is the first example of organocatalytic intermolecular reaction realizing atropselective benzene formation. The reaction employs readily available starting materials and provides rapid access to optically pure atropisomeric arenes. The enantioselectivity is excellent even when the steric differences are very small among the chiral axial (similar R2&R3). The organic oxidant can be made catalytic by using electrochemical oxidative regeneration. In short, our atropselective reaction expands the synthetic potential of NHC asymmetric catalysis and provides a competitive pathway for the synthesis of axially chiral functional molecules

References 1. Link, A.; Sparr, C. Chem. Soc. Rev., 2018, 47, 3804. 2. Domínguez, G.; Pérez-Castells, J. Chem. Soc. Rev. 2011, 40, 3430. 3. Xu, K.; Li, W.; Zhu, S.; Zhu, T. Angew. Chem. Int. Ed. 2019, 10.1002/anie.201910049

Ting-Shun Zhu. Shanghai Institute of Materia Medica (PhD, 2006-2012). Nanyang Technological University (Research Fellow, 2012-2017). Sun Yat-Sen University (Professor, 2017-present). [Field of research] Asymmetric catalysis, NHC organocatalysis, Electrochemical organic synthesis

124