DOCSLIB.ORG

Asymmetric Hydrogenation of Esters and Efforts Towards Photohydrogenation

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Asymmetric Hydrogenation of Esters and Efforts Towards Photohydrogenation Asymmetric Hydrogenation of Esters and Efforts Towards Photohydrogenation by Riley Thomas Endean A thesis submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy Department of Chemistry University of Alberta © Riley Thomas Endean, 2020 Abstract A thorough overview of esters and their reductions is presented. A large focus was placed on reductions via homogeneous catalytic hydrogenation. Although several ester hydrogenation systems have been developed, the production of highly enantioenriched alcohols has generally relied upon the usage of enantioenriched esters. A system for homogeneous asymmetric hydrogenation of esters to enantioenriched alcohols was discovered and optimized via an in-house screening method. The optimal system 5 6 uses an in situ formed Ru-based catalyst made from [Ru(1-3:5,6-η -C8H11)(η -anthracene)]BF4, the chiral ligand (1R,2R)-N,N′-bis{2-[bis(3,5-dimethylphenyl)phosphino]benzyl}cyclohexane- 1,2-diamine, and H2. This catalyst is highly active and enantioselective towards hydrogenating α-phenoxy esters to β-chiral primary alcohols under mild conditions. The system operates via dynamic kinetic resolution (DKR), where the esters undergo base-assisted racemization and the catalyst preferentially reacts with one enantiomer. Specifically, NaOiPr in THF and NaOEt in DME were optimal base and solvent combinations for the DKR. The alkoxide bases participate in transesterification and catalyst activation. Under 4 atm H2 and at room temperature, the catalyst provides quantitative conversion (50 turnovers) over 1 h for α-phenoxy propionate and butyrate esters (2 mol% catalyst, 50 mol% base). The enantiomeric excesses of the resulting β-chiral alcohols ranged from 79 to 93%. The hydrogenation of (±)-ethyl 2-phenoxypropionate at 0 C resulted in a 95% enantiomeric excess (ee). Under 15 atm H2 and at room temperature, the catalyst performed 950 turnovers of (±)-ethyl 2-phenoxypropionate over 9 h and resulted in a 91% ee towards (R)-2-phenoxypropan-1-ol (0.1 mol% catalyst, 20 mol% NaOEt, DME). Hydrogenation of the potential intermediate aldehyde (±)-2-phenoxypropionaldehyde and ii deuteration of (±)-ethyl 2-phenoxypropionate were performed to experimentally investigate the mechanism. Three Ru(II)–polypyridyl complexes were prepared for the underexplored area of photohydrogenation. [Ru(bipy)2(1,10-phenanthroline-5,6-diamine)](OTf)2 (bipy = 2,2′-bipyridine) was synthesized in 56% yield from [Ru(MeCN)2(bipy)2](OTf)2 and the bis-bidentate ligand 1,10-phenanthroline-5,6-diamine in MeOH at 70 C. The dinuclear complex was not the major product. The imidazolium ligand 1-benzyl-3-(propan-2-yl)-1H-imidazol[4,5- f][1,10]phenanthroline-3-ium (bpip) was prepared in 55% yield over three steps from 1,10-phenanthroline-5,6-diamine. The complexation of bpip to the Ru–dichloride precursors cis-[Ru(Cl)2(bipy)2] and cis-[Ru(Cl)2(dmbipy)2] (dmbipy = 4,4′-dimethyl-2,2′-bipyridine) proceeded smoothly in MeOH at 70 C. [Ru(bpip)(bipy)2](OTf)3 and [Ru(bpip)(dmbipy)2](OTf)3 were prepared from their respective dichloride precursors, over two steps, in 87 and 73% yields, respectively. Crystals suitable for X-ray diffraction were obtained for [Ru(bpip)(bipy)2](BF4)3. The [Ru(bipy)2(1,10-phenanthroline-5,6-diamine)](OTf)2 and [Ru(bpip)(dmbipy)2](OTf)3 were incorporated into two separate known hydrogenation systems. The photohydrogenation of acetophenone was attempted with in situ catalyst formation from i [Ru(bipy)2(1,10-phenanthroline-5,6-diamine)](OTf)2 and fac-[Ru((R)-BINAP)(H)( PrOH)3]BF4 (BINAP = 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl). Only ~2% of the acetophenone was t i converted (~10 turnovers) over 45 min (0.2 mol% catalyst, 10 mol% KO Bu, PrOH, ~1 atm H2, rt, 15 min 400–700 nm hv). The photohydrogenation of styrene was attempted with in situ catalyst formation from [Ru(bpip)(dmbipy)2](OTf)3 and [Co(TMEDA)(CH2SiMe3)] (TMEDA = N,N,N′,N′-tetramethylethylenediamine). No detectable reaction occurred under the conditions t examined (0.2 mol% catalyst, 0.2 mol% KO Bu, MeOH, ~1 atm H2, 450 nm hv, 10.5 h). iii Preface A portion of the data presented in this dissertation was acquired in collaboration with other researchers within the Department of Chemistry at the University of Alberta. All HRMS analyses were performed by staff members in the Mass Spectrometry Laboratory. All elemental analyses were performed by staff members in the Analytical and Instrumentation Laboratory. Chapter 1 is an introductory chapter that presents a significant amount of data involving esters. The data presented is that of the respective referenced authors. Reaction and mechanistic schemes were drawn or redrawn by Riley Endean. Copyright permissions were obtained for redrawn tables and mechanistic schemes. Chapter 2 has been adapted and expanded upon from the following publication: Endean R. T.; Rasu L.; Bergens S. H. Enantioselective Hydrogenations of Esters with Dynamic Kinetic Resolution. ACS Catal. 2019, 9 (7), 6111–6117. Riley Endean performed most of the reactions and data collection. Dr. Loorthuraja Rasu participated in the development of the screening method and initial ligand screenings. Dr. Rasu also synthesized (±)-ethyl 2-phenoxypropionate and (±)-butan-2-yl-phenoxypropionate. The reported syntheses of (±)-ethyl 2-phenoxypropionate are that performed by Riley Endean. Steven H. Bergens was the supervisory author. The NMR spectra from the ester deuteration study were acquired with the aid of Mark Miskolzie from the NMR Laboratory at the University of Alberta. Chapter 3 is unpublished work that was performed in collaboration with James Pearson. Specifically, James Pearson assisted with the development of the imidazolium salts. All syntheses reported are those performed by Riley Endean. The NMR data were collected by Riley Endean. The X-ray crystallographic study was performed by Dr. Michael Ferguson from the X-ray Crystallography Laboratory. The crystal and refinement data were collected by Dr. Ferguson. Chapter 4 is unpublished and independent work by Riley Endean. Chapter 5 is a summary and possible future research directions. iv Acknowledgements There are many people that deserve recognition for supporting me while at the University of Alberta. Several professors have contributed to my development as a scientist. First and foremost, my supervisor Prof. Steven Bergens has been an invaluable source of knowledge, guidance, and enthusiasm. I am grateful for his positive and humorous attitude. To my supervisory committee members Prof. Eric Rivard and Prof. Jonathan Veinot, I sincerely appreciate your various involvement and advice. I would also like to thank Prof. Arthur Mar for being part of my candidacy examination committee and Prof. Rylan Lundgren for serving on both my candidacy and final examination committees. I am also appreciative of my non-examining committee members Prof. Josef Takats and Prof. Robert Jordan. I am greatly appreciative of Prof. Jennifer Love for serving as my external examiner. I am extremely appreciative of the time and effort that each professor put into reviewing this dissertation. To past and present Bergens group members, your advice, support, and friendship has been incredibly important to me. A special thanks to Dr. Loorthuraja Rasu who has served as a mentor, trainer, and friend. I would also like to specifically express gratitude towards Dr. Mona Amiri, Dr. Chao Wang, Dr. Shuai Xu, Suneth Kalapugama, Prabin Nepal, Octavio Martinez Perez, James Pearson, Jinkun Liu, Benjamin Rennie, and Emily Majaesic for their years of friendship. There are various staff that also deserve recognition. Thank you to my teaching assistant coordinators Dr. Yoram Apelblat, Dr. Norman Gee, and Dr. Alexandra Faucher. I thoroughly enjoyed my teaching assistant experience and learnt a lot. I would like to acknowledge Mark Miskolzie for his exceptional NMR services, knowledge, and his unique friendliness. I also appreciate Dr. Ryan McKay and Nupur Dabral for their NMR services. I would like to thank Dr. Michael Ferguson from the X-ray Crystallography Laboratory. I would like to express gratitude towards everyone from the Mass Spectrometry Laboratory and the Analytical and Instrumentation Laboratory. I would also like to thank all of the support staff members. A particular thank you goes to Anuar Rivero and Scott Stelck for dealing with my various purchases throughout the years. I would like to thank Ryan Lewis, Michael Barteski, Matthew v Kingston, and Bernie Hippel for providing amusing interactions while working. I would also like to thank the other chemical stores and receiving staff. I would like to thank the Machine Fabrication staff. Specifically, Dirk Kelm and Paul Crothers for dealing with various mechanical issues. A significant thank you goes to Kim Do, Andrew Hillier, Broderick Wood, and Cameron Ridderikhoff for various fixes to my invaluable GC–MS system running Windows 3.0. I would also like to acknowledge Anita Weiler for her assistance throughout the years. Several friends from other groups have made my life better. There are too many to mention, but I would like to recognize Christina Braun, Benjamin Rehl, Carl Estrada, Christopher Cooze, Wesley McNutt, Alvaro Omaña, and Ian Watson for being great people. A special recognition goes to Anis Fahandej-Sadi for being an awesome friend and gym partner. Another special recognition goes to my roommate for two years and longtime friend, Trevor Johnson. I also want to thank Devin Chattu for being a great friend and always welcoming me back to my hometown. An incredibly important recognition goes to Kelsey Grant, who has been a great friend, roommate, and partner. Her support during my degree was instrumental to my sanity and success. Last but not least, my family has been extremely supportive throughout my life. Samantha you are an incredibly caring sister, and I am very proud to be your brother. I am also proud to be the son of two incredible people.
Load more

Recommended publications
  • Palladium-Catalyzed Tsuji-Trost Allylation of J-Borylated Allyl Acetates
    ANNÉE 2013 THÈSE / UNIVERSITÉ DE RENNES 1 sous le sceau de l’Université Européenne de Bretagne pour le grade de DOCTEUR DE L’UNIVERSITÉ DE RENNES 1 Mention : CHIMIE Ecole doctorale Sciences de la Matière de Rennes présentée par Krishna Kishore Kukkadapu UMR 6510 CNRS Chimie et Photonique Moléculaires UFR Sciences et Propriétés de la Matière Thèse soutenue à Rennes Gamma-borylated le Jeudi 6 juin 2013 allylic acetates as 3 devant le jury composé de : Véronique BELLOSTA carbon functionalized Professeur –ESPCI / rapporteur units : synthesis and Stéphane PELLET-ROSTAING Chargé de recherche CNRS à l’ICSM-CEA / applications rapporteur Florence MONGIN Professeur à l’Université de Renne1 / / examinateur Mathieu PUCHEAULT Chargé de recherche CNRS / examinateur Michel VAULTIER Directeur de recherche CNRS/ / directeur de thèse 1 Table of contents : Résumé de la thèse en français 5 Acknowledgements: 22 Abbreviations: 24 General Introduction: 27 PART ͲA 30 Chapter I: Bibliography 30 I. 1. Synthesis &applications of JͲborylated allylic electrophiles: 31 I. 1. i. Synthesis of JͲborylated allylic electrophiles: 31 I. 1. ii. Applications of JͲborylated allylic electrophiles: 33 I. 1. ii. a. In iridium catalysis: 33 I. 1. ii. b. In copper catalysis: 37 I. 1. ii. c. In palladium catalysis: 39 I. 1. ii. d. In Grignard reaction: 41 I. 1. ii. e. In Diels Alder reaction: 42 I. 1. ii. f. In Mitsunobu reaction: 43 I. 1. ii. g. In cyclopropane synthesis: 46 I. 2. Tsuji ͲTrost Allylation: 48 I. 2. i. Stereochemistry in Tsuji ͲTrost allylation: 51 I. 2. ii. Regioselectivity in Tsuji ͲTrost allylation: 52 I. 2. iii.
    [Show full text]
  • Stretchable Chiral Pockets for Palladium-Catalyzed Highly Chemo- and Enantioselective Allenylation ✉ ✉ Yuchen Zhang1, Xue Zhang2 & Shengming Ma 1,2
    ARTICLE https://doi.org/10.1038/s41467-021-22498-1 OPEN Stretchable chiral pockets for palladium-catalyzed highly chemo- and enantioselective allenylation ✉ ✉ Yuchen Zhang1, Xue Zhang2 & Shengming Ma 1,2 Pyrazolones are a vital class of heterocycles possessing various biological properties and much attention is paid to the diversified synthesis of enantiopure pyrazolone derivatives. We describe here the development of diphenylphosphinoalkanoic acid based chiral bisphosphine 1234567890():,; ligands, which are successfully applied to the palladium-catalyzed asymmetric allenylation of racemic pyrazol-5-ones. The reaction affords C-allenylation products, optically active pyrazol- 5-ones bearing an allene unit, in high chemo- and enantioselectivity, with DACH-ZYC-Phos- C1 as the best ligand. The synthetic potential of the C-allenylation products is demonstrated. Furthermore, the enantioselectivity observed with DACH-ZYC-Phos-C1 is rationalized by density functional theory studies. 1 Laboratory of Molecular Recognition and Synthesis, Department of Chemistry, Zhejiang University, Hangzhou, Zhejiang, P. R. China. 2 State Key Laboratory ✉ of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, P. R. China. email: [email protected]; [email protected] NATURE COMMUNICATIONS | (2021) 12:2416 | https://doi.org/10.1038/s41467-021-22498-1 | www.nature.com/naturecommunications 1 ARTICLE NATURE COMMUNICATIONS | https://doi.org/10.1038/s41467-021-22498-1 yrazolones are a vital class of heterocycles possessing various with 84% ee (Fig. 2, entries 1–5). After optimizing the tempera- Pbiological properties1. Of particular interest are the pyr- ture and concentration (Fig. 2, entries 6–11), the reaction at 0.02 azolone derivatives with a chiral center (Fig.
    [Show full text]
  • Chiral Amino–Phosphine and Amido–Phosphine Complexes of Ir and Mg. Catalytic Applications in Olefin Hydroamination
    Zurich Open Repository and Archive University of Zurich Main Library Strickhofstrasse 39 CH-8057 Zurich www.zora.uzh.ch Year: 2016 Chiral amino-phosphine and amido-phosphine complexes of Ir and Mg. Catalytic applications in olefin hydroamination Schmid, Bernhard ; Frieß, Sibylle ; Herrera, Alberto ; Linden, Anthony ; Heinemann, Frank W ; Locke, Harald ; Harder, Sjoerd ; Dorta, Romano DOI: https://doi.org/10.1039/c6dt01146b Posted at the Zurich Open Repository and Archive, University of Zurich ZORA URL: https://doi.org/10.5167/uzh-125944 Journal Article Accepted Version Originally published at: Schmid, Bernhard; Frieß, Sibylle; Herrera, Alberto; Linden, Anthony; Heinemann, Frank W; Locke, Harald; Harder, Sjoerd; Dorta, Romano (2016). Chiral amino-phosphine and amido-phosphine complexes of Ir and Mg. Catalytic applications in olefin hydroamination. Dalton Transactions, 45(30):12028-12040. DOI: https://doi.org/10.1039/c6dt01146b Chiral Amino–Phosphine and Amido–Phosphine Complexes of Ir and Mg. Catalytic Applications in Olefin Hydroamination Bernhard Schmid, † Sibylle Frieß, † Alberto Herrera,† Anthony Linden,‡ Frank W. Heinemann, Harald Locke, Sjoerd Harder, Romano Dorta* Department Chemie und Pharmazie, Anorganische und Allgemeine Chemie, Friedrich–Alexander– Universität Erlangen–Nürnberg, Egerlandstraße 1, 91058 Erlangen, Germany [email protected] ‡) Institut für Chemie, Universität Zürich, Winterthurerstrasse 190, CH-8057, Zurich, Switzerland †) Authors contributed equally to this publication. Abstract The reactions of rac- and (S,S)-trans-9,10-dihydro-9,10-ethanoanthracene-11,12-diamine (ANDEN) with PClPh2 in the presence of NEt3 yield the chiral amino-phosphine ligands rac-6 and (S,S)-6, respectively, on multi-gram scales. Both forms of 6 react quantitatively with MgPh2 to afford the C2– symmetric, N–bound Mg amidophosphine complexes rac-7 and (S,S)-7.
    [Show full text]
  • 402 the Development of an Asymmetric Tsuji Allylation
    402 CHAPTER FOUR The Development of an Asymmetric Tsuji Allylation Reaction† 4.1 Introduction The catalytic asymmetric synthesis of all-carbon quaternary stereocenters stands as a significant challenge in synthetic chemistry.1 Despite the demanding sterics, a number of useful catalytic transformations, including Diels-Alder,2 Heck,3 cyclopropanation,4 alkylation,5 acylation,6 and desymmetrization7 reactions, have been demonstrated to form quaternary stereocenters with good levels of enantioinduction. Although palladium-catalyzed enantioselective allylation chemistry has long been an important asymmetric catalytic tool,8 only recently has palladium (II) -allyl chemistry been used for the formation of quaternary stereocenters. The vast majority of palladium (II) allylic alkylations studied by Trost, Helmchen, Pfaltz, and others form tertiary stereocenters by the attack of malonate anions on prochiral 1,3-disubstituted allyl fragments. Helmchen has shown that such reactions with palladium phosphinooxazoline (PHOX) complexes typically occur via an outer sphere malonate attack at the allyl termini.9 The tendency of palladium to give the less branched products in allylic alkylations with differentially substituted allyl termini makes the formation of quaternary stereocenters on the allyl fragment problematic.10 An alternative, less common strategy in allylic alkylation is the use of prochiral nucleophiles. A quaternary stereocenter may formed on the prochiral nucleophile when it possesses three distinct carbon substituents. A priori, such reactions requiring the remote † This work was performed in collaboration with Justin Mohr, Dr. Andrew Harned, Dr. Kousuke Tani, Dr. Zoltán Novák, Sandy Ma, Nathaniel Sherden, Mike Krout, and Ryan McFadden. 403 chiral ligand to discriminate between the prochiral faces of the incoming nucleophile seem improbable.
    [Show full text]
  • Transition Metal Catalysed Reactions for the Synthesis of Heteroaromatic Compounds
    Transition Metal Catalysed Reactions for the Synthesis of Heteroaromatic Compounds Stephen Christopher Pelly A thesis submitted to the Faculty of Science, University of the Witwatersrand, Johannesburg In fulfilment of the requirements for the Degree of Doctor of Philosophy January 2007 DECLARATION I declare that the work presented in this thesis was carried out exclusively by myself under the supervision of Professor C.B. de Koning. It is being submitted for the degree of Doctor of Philosophy in the University of the Witwatersrand, Johannesburg. It has not been submitted before for any degree or examination in any other University. _________________ 27th day of January, 2007 i ABSTRACT The carbazole and 2-isopropenyl-2,3-dihydrobenzofuran structures are widely found in many naturally occurring compounds. For example, the naturally occurring anti-cancer compound, rebeccamycin, contains an indolocarbazole core. Rotenone, which contains an (R)-2-isopropenyl-2,3-dihydrobenzofuran moiety, is widely used today as an effective naturally occurring pesticide. In the carbazole section of this thesis, the synthesis of the naturally occurring furanocarbazole, furostifoline is described. As key steps in this sequence, a Suzuki coupling reaction is utilised to couple appropriately functionalised indole and furan moieties. After further functional group transformations, a metathesis reaction is employed to construct the carbazole system, leading to furostifoline. The synthesis of the unnatural thio-analogue of furostifoline was similarly conducted and is described. Finally, in a somewhat different approach, the synthesis of the indolocarbazole core is described, utilising a Madelung approach initially to form the bis-indole system, 2,2’-biindolyl. After several functional group transformations, a metathesis reaction was once again successfully employed to form the carbazole system, thereby synthesising di(tert-butyl) indolo[2,3-a]carbazole-11,12-dicarboxylate.
    [Show full text]
  • US8513234.Pdf
    USOO851.3234B2 (12) United States Patent (10) Patent No.: US 8,513,234 B2 Isaacs et al. (45) Date of Patent: Aug. 20, 2013 (54) HIV INTEGRASE INHIBITORS 7,217,713 B2 5/2007 Crescenzi et al. 7,232,819 B2 6/2007 Di Francesco et al. 7,273,859 B2 9, 2007 Naidu (75) Inventors: Richt C. E. AARA 7,279.487 B2 10/2007 Egbertson et al. (US), Wayne J. Thompson, Lansdale, 7,414,045 B2 8/2008 Crescenzi et al. PA (US); Peter D. Williams, 7,419,969 B2 9/2008 Naidu et al. Harleysville, PA (US); Dai-Shi Su, 7,435,734 B2 10/2008 Crescenzi et al. Dresher, PA (US); Shankar 7,494.984 B2 2/2009 Banville et al. s s 7,504.405 B2 3/2009 Wang et al. Venkatraman, Lansdale, PA (US); 2004/0229909 A1 1 1/2004 Kiyama et al. Mark W. Embrey, Harleysville, PA 2007/0083045 A1 4/2007 Di Francesco et al. (US); Thorsten E. Fisher, Hatfield, PA 2007/011 1984 A1 5, 2007 Naidu et al. (US); John S. Wai, Harleysville, PA 2007/011 1985 A1 5, 2007 Naidu et al. (US); David C. Dubost, Collegeville, PA (Continued) (US); Richard G. Ball, Edison, NJ (US); Eric J. Choi, Westfield, NJ (US); Tao FOREIGN PATENT DOCUMENTS Pei, Morganville, NJ (US); Sarah L. EP 1698.628 A1 9, 2006 Trice, Glenside, PA (US); Neil WO 2005/061501 A2 7/2005 Campbell, Cherry Hill, NJ (US); (Continued) Matthew Maddess, Boston, MA (US); Peter E. Maligres, Fanwood, NJ (US); OTHER PUBLICATIONS Michael Shevlin, Plainfield, NJ (US); Ferrara et al.
    [Show full text]
  • Magnetic Hybrid Materials Based on Co/C Nanoparticles and Their Use in Catalysis
    Magnetic Hybrid Materials based on Co/C Nanoparticles and their Use in Catalysis Dissertation Zur Erlangung des Doktorgrades der Naturwissenschaften Dr. rer. nat. der Fakultät für Chemie und Pharmazie der Universität Regensburg vorgelegt von Benjamin Kastl aus Burglengenfeld Regensburg 2018 Die Arbeit wurde angeleitet von: Prof. Dr. Oliver Reiser Promotionsgesuch eingereicht am: 12.06.18 Promotionskolloquium am: Prüfungsauschuss: Vorsitz: Dr. Rainer Müller 1. Gutachter: Prof. Dr. Oliver Reiser 2. Gutachter: Prof. Dr. Rehbein 3. Gutachter: Prof. Dr. Frank-Michael Matysik Der experimentelle Teil der vorliegenden Arbeit wurde im Zeitraum von November 2014 bis November 2017 unter der Anleitung von Prof. Dr. Oliver Reiser am Institut für Organische Chemie der Universität Regensburg angefertigt. Besonders bedanken möchte ich mich bei Herrn Prof. Dr. Oliver Reiser für die Aufnahme in seinen Arbeitskreis, die Überlassung des interessanten Themas, die anregenden Diskussionen und die stete Unterstützung. Meiner Familie “Wissenschaft ist Magie, die funktioniert.” Kurt Vonnegut (1922 – 2007) Table of contents A. Introduction ........................................................................................................................ 4 1. Magnetic nanoparticles: materials and functionalization .............................................. 5 2. Carbon-coated cobalt nanoparticles ............................................................................... 7 3. References ....................................................................................................................
    [Show full text]
  • | Hao Wakat I Maria Del Con at Malaman
    |HAO WAKAT I MARIAUS009937186B2 DEL CON AT MALAMAN NAT (12 ) United States Patent (10 ) Patent No. : US 9 , 937 , 186 B2 Ohlmeyer et al. (45 ) Date of Patent: Apr. 10 , 2018 ( 54 ) SULFONAMIDES DERIVED FROM USPC .. .. .. .. .. 514 / 217 TRICYCLYL - 2 - AMINOCYCLOALKANOLS See application file for complete search history . AS ANTICANCER AGENTS ( 71 ) Applicant: ICAHN SCHOOL OF MEDICINE ( 56 ) References Cited AT MOUNT SINAI, New York , NY U . S . PATENT DOCUMENTS (US ) 4 ,634 ,766 A 1 / 1987 Atkinson et al. (72 ) Inventors : Michael Ohlmeyer , Plainsboro , NJ 4 ,668 ,671 A 5 / 1987 Gribble et al . (US ) ; David Kastrinsky , Fair Lawn, NJ 4 , 882 , 351A 11/ 1989 Oshima et al . 6 ,583 , 138 B1 6 /2003 Miyamoto et al . (US ) 9 , 540 , 358 B2 1 / 2017 Ohlmeyer et al. 2002/ 0103189 A18 / 2002 Miyamoto et al. @(73 ) Assignee : ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI, New York , NY 2008/ 0275023 Al 11/ 2008 Guidi et al . (US ) (Continued ) ( * ) Notice : Subject to any disclaimer , the term of this FOREIGN PATENT DOCUMENTS patent is extended or adjusted under 35 CN 102942562 A 2 /2013 U . S . C . 154 (b ) by 0 days . EP 0679641 A1 11 / 1995 (21 ) Appl. No. : 15 /124 , 891 (Continued ) ( 22 ) PCT Filed : Mar. 10 , 2015 OTHER PUBLICATIONS Zhang et al, “ Akt, FoxO and regulation of apoptosis, ” Biochimica ( 86 ) PCT No .: PCT/ US2015 /019770 et Biophysica Acta , 2011 , vol. 1813 , pp . 1978 -1986 . * $ 371 (c ) ( 1 ) , (Continued ) ( 2 ) Date : Sep . 9 , 2016 (87 ) PCT Pub . No. : WO2015 / 138500 Primary Examiner — Kathrien A Cruz Assistant Examiner — Janet L . Coppins PCT Pub .
    [Show full text]
  • Development of Palladium-Catalyzed Decarboxylative Benzylation Reactions
    Syntheses of Functionalized Benzylic Compounds: Development of Palladium-catalyzed Decarboxylative Benzylation Reactions by Robert Ryan Pangilinan Torregrosa B.S. Chemistry, University of Santo Tomas, Manila Philippines, 2005 Submitted to the Department of Chemistry and the Faculty of the Graduate School of The University of Kansas in partial fulfillment of the requirements for the degree of Doctor of Philosophy _______________________________ Jon A. Tunge, chairperson _______________________________ Paul R. Hanson _______________________________ Richard S. Givens _______________________________ David R. Benson _______________________________ Apurba Dutta Date Defended: July 24, 2012 The Dissertation Committee for Robert Ryan Pangilinan Torregrosa certifies that this is the approved version of the following dissertation: Syntheses of Functionalized Benzylic Compounds: Development of Palladium-catalyzed Decarboxylative Benzylation Reactions _______________________________ Jon A. Tunge, chairperson _______________________________ Paul R. Hanson _______________________________ Richard S. Givens _______________________________ David R. Benson _______________________________ Apurba Dutta Date Defended: July 24, 2012 ii Abstract Robert R. P. Torregrosa Department of Chemistry, July 2012 The University of Kansas Carbon-carbon bond formation between the benzyl carbon and a functional group is important in organic synthesis because majority of the compounds in the chemical literature contain aromatic cores appended with different functionalities
    [Show full text]
  • Molecular Mechanics (MM) 23
    Downloaded from orbit.dtu.dk on: Oct 01, 2021 Selective Homogeneous Catalysis in Asymmetric Synthesis Fristrup, Peter Publication date: 2006 Document Version Publisher's PDF, also known as Version of record Link back to DTU Orbit Citation (APA): Fristrup, P. (2006). Selective Homogeneous Catalysis in Asymmetric Synthesis. Technical University of Denmark. General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. Users may download and print one copy of any publication from the public portal for the purpose of private study or research. You may not further distribute the material or use it for any profit-making activity or commercial gain You may freely distribute the URL identifying the publication in the public portal If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Peter Fristrup Selective Homogeneous Catalysis in Asymmetric Synthesis Ph. D. Thesis DTU, Lyngby, February 2006. Cover: Illustration of the new mnemonic device for prediction of absolute configuration in the osmium- catalyzed asymmetric dihydroxylation. A transition state structure incorporating one of the substrate probes is used to illustrate the molecular structure. ii Peter Fristrup Selective Homogeneous Catalysis in Asymmetric Synthesis Ph.D. Thesis, February 2006 Department of Chemistry Technical University of Denmark iii Preface This thesis is submitted in candidacy for the Ph.D. degree from the Technical University of Denmark (DTU).
    [Show full text]
  • Palladium-Catalyzed Enantioselective Allylic Substitutions on Bifunctional Substrates
    Palladium-catalyzed Enantioselective Allylic Substitutions on Bifunctional Substrates Inauguraldissertation zur Erlangung der Würde eines Doktors der Philosophie vorgelegt der Philosophisch-Naturwissenschaftlichen Fakultät der Universität Basel von Stéphanie Angèle Richoz aus Ursy (FR), Schweiz Basel, 2012 Originaldokument gespeichert auf dem Dokumentenserver der Universität Basel edoc.unibas.ch Dieses Werk ist unter dem Vertrag „Creative Commons Namensnennung-Keine kommerzielle Nutzung-Keine Bearbeitung 2.5 Schweiz“ lizenziert. Die vollständige Lizenz kann unter creativecommons.org/licences/by-nc-nd/2.5/ch eingesehen werden. Genehmigt von der Philosophisch-Naturwissenschaftlichen Fakultät auf Antrag von Prof. Dr. Murat Acemoglu Prof. Dr. Andreas Pfaltz Prof. Dr. Wolf-Dietrich Woggon Basel, den 26. Juni 2012 Prof. Dr. Martin Spiess Dekan Namensnennung-Keine kommerzielle Nutzung-Keine Bearbeitung 2.5 Schweiz Sie dürfen: das Werk vervielfältigen, verbreiten und öffentlich zugänglich machen Zu den folgenden Bedingungen: Namensnennung. Sie müssen den Namen des Autors/Rechteinhabers in der von ihm festgelegten Weise nennen (wodurch aber nicht der Eindruck entstehen darf, Sie oder die Nutzung des Werkes durch Sie würden entlohnt). Keine kommerzielle Nutzung. Dieses Werk darf nicht für kommerzielle Zwecke verwendet werden. Keine Bearbeitung. Dieses Werk darf nicht bearbeitet oder in anderer Weise verändert werden. • Im Falle einer Verbreitung müssen Sie anderen die Lizenzbedingungen, unter welche dieses Werk fällt, mitteilen. Am Einfachsten ist es, einen Link auf diese Seite einzubinden. • Jede der vorgenannten Bedingungen kann aufgehoben werden, sofern Sie die Einwilligung des Rechteinhabers dazu erhalten. • Diese Lizenz lässt die Urheberpersönlichkeitsrechte unberührt. Die gesetzlichen Schranken des Urheberrechts bleiben hiervon unberührt. Die Commons Deed ist eine Zusammenfassung des Lizenzvertrags in allgemeinverständlicher Sprache: http://creativecommons.org/licenses/by-nc-nd/2.5/ch/legalcode.de Haftungsausschluss: Die Commons Deed ist kein Lizenzvertrag.
    [Show full text]
  • Pd-Η3-C6H9 Complexes of the Trost Modular Ligand
    Chemical Science View Article Online EDGE ARTICLE View Journal | View Issue 3 Pd-h -C6H9 complexes of the Trost modular ligand: high nuclearity columnar aggregation controlled Cite this: Chem. Sci.,2015,6,5793 by concentration, solvent and counterion† Daugirdas Tomas Racys,‡a Julian Eastoe,a Per-Ola Norrby,bc Isabelle Grillo,d Sarah E. Rogerse and Guy C. Lloyd-Jones*f Under optimised conditions, the Trost modular ligand (TML) series induces high levels of asymmetric induction in an extraordinarily wide range of reactions involving palladium p-allyl intermediates. Prior 3 mechanistic investigations into reactions involving Pd-h -C6H9 intermediates have focussed on the monomeric 13-membered ring formed via P,P-chelation of the ligand to Pd. However, it is also 3 recognised that ring-opening oligomerisation provides a pool of high nuclearity Pd-h -C6H9 species that, by affording a low level, or even the opposite sense, of asymmetric induction relative to the mononuclear species, are responsible for a reduction in selectivity under non-optimised conditions. Creative Commons Attribution 3.0 Unported Licence. Herein we describe an investigation by NMR spectroscopy, molecular mechanics, molecular dynamics, 3 and small-angle neutron scattering (SANS), of a Pd-h -C6H9 cation bearing the 1,2-diaminocyclohexane Received 2nd April 2015 TML ligand (2). Using both nondeuterated and perdeuterated (D ) isotopologues of the resulting Accepted 12th June 2015 47 complexes ([1]+), we show that a two-stage oligomerisation-aggregation process forms self assembled DOI: 10.1039/c5sc01181g cylindrical aggregates of very high nuclearity (up to 56 Pd centres). We also investigate how www.rsc.org/chemicalscience concentration, solvent and counter-anion all modulate the extent of oligomerisation.
    [Show full text]