DOCSLIB.ORG

PALLADIUM-PEPPSI-Ipentcl; a USEFUL CATALYST for CHALLENGING AMINATION REACTIONS

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
PALLADIUM-PEPPSI-Ipentcl; a USEFUL CATALYST for CHALLENGING AMINATION REACTIONS PART I: PALLADIUM-PEPPSI-IPENTCl; A USEFUL CATALYST FOR CHALLENGING AMINATION REACTIONS PART II: GENERATION OF BENZYNES IN FLOW REACTORS FOLLOWED BY SUBSEQUENT DIELS-ALDER REACTIONS ABIR ALI KHADRA A DISSERTATION SUBMITTED TO THE FACULTY OF GRADUATE STUDIES IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY GRADUATE PROGRAM IN CHEMISTRY YORK UNIVERSITY TORONTO, CANADA MAY, 2018 © ABIR ALI KHADRA, 2018 ABSTRACT: The first part of this research focuses on developing efficient methods to address challenging Buchwald –Hartwig amination reactions using Pd-NHC pre-catalysts. Specifically, we focused on: a) coupling of sterically hindered primary and secondary amines and b) coupling of 2-aminopyridine derivatives with aryl and heteroaryl halides. Although several approaches have been developed and proven to be effective for coupling of sterically hindered amines, they have limited utility and substrate scope. Pd-PEPPSI-IPentCl (Pyridine Enhanced Pre-catalyst Preparation Stabilization and Initiation) proved to be a very effective catalyst for coupling hindered primary and secondary amines under mild reaction conditions (i.e. Na-BHT (BHT = 2,6-Di-tert-butyl hydroxyl toluene), 80 °C, DME) tolerating base sensitive functional groups such as ester, keto, and nitrile groups. While the synthesis of 2-aminopyridine derivatives is commonly carried out by metal-catalyzed coupling of 2-halopyridines with aniline derivatives, the use of 2-aminopyridine as a nucleophilic partner in Pd catalysis is very difficult as these substrates tend to bind irreversibly to the palladium center and shut down the catalytic cycle. However, Pd-PEPPSI-IPentCl has been found to resist the binding of 2-aminopyridines, making it a very active catalyst for these couplings. The steric bulk of the 3-pentyl substituents on the aryl rings of the NHC ligand that drives the cross-coupling by facilitating reductive elimination also mitigates the poisoning effect of the 2-aminopyridine functionality in the starting material/and or products. We also found that placing electron-donating or electron-withdrawing substituents at the 6-position of the 2-aminopyridine ring reduces the poisoning effect and facilitate the catalytic cycle with mild bases (i.e. Na-BHT). ii The second part of this research investigated the formation of benzyne derivatives from ortho-trimethylsilyl triflates using tetra-n-butylammonium fluoride (TBAF) as the benzyne- forming trigger in the flow system. The numerous advantages of microfluidic devices enabled the formation of these species at room temperature which were immediately trapped in Diels-Alder reactions with five-membered heterocyclic dienes to generate bicyclic alkenes of biological interest. The yields of Diels-Alder reaction with benzynes follow the order: furans > pyrroles > thiophene. iii Dedications It is my genuine gratefulness and warmest regard that I dedicate this thesis to my friend Suzann Mansour, her kindness and devotion, her inspiration throughout the years of our friendship will not be forgotten. Suzann; you left incredible fingerprints of grace in my life, wish you were here. I also dedicate my work to my daughter Celina, I am truly thankful to have you in my life. iv ACKNOWLEDGMENTS First, I would like to express my special thanks to my supervisor Prof. Michael G. Organ for providing me with a golden opportunity to be one of his graduate students. The free environment that he provides to his students to work independently, to be creative and to develop problem- solving skills allowed me to be a much more confident chemist that I would imagine. Also, I would like to extend my thanks to Prof. Arturo Orellana for his constructive criticism, sharing his valuable knowledge in organic chemistry during my research evaluations at the end of each year, and during the problem sessions. His support and encouragement were extremely valuable especially when I became a new mother. In addition, I would like to thank Prof. Pierre Potvin for agreeing to be my research committee, his fruitful suggestions and advice in the lab during my CHEM 4000 course enabled me to be well prepared for graduate school. Next, I would like to thank Dr. Howard Hunter for his willingness to help and share his immense knowledge in NMR spectroscopy, his patience to answer my endless questions especially at the beginning of my studies, and his attempts to cheer me up whenever a reaction does not work. I would like to express my gratitude to my colleagues that I have had the pleasure to work with, especially to my best friends Sepideh Sharif who stood by me and helped me through the difficult times, to Xia Chen and many discussions about food and calorie counting, to Kristina Somerville- Rucker with her rare sense of humor, lovely spirit that forces you to smile no matter what. To my wise and loyal friend Zahra Vaziri who was always there for me especially during my pregnancy; to Dr. Jennifer Farmer and her valuable advices to cope stress; to an amazing friend Dr. George Achonduh; to Dr. Niloufar Hadie and her incredible sense of humor and her passion to live life to the maximum; to Matthew Pompeo and his unique professionalism; to Andrei Nikolaev and his passion to organic chemistry and willingness to participate in discussion on reaction mechanisms v for hours and hours; to Nour Bizzari and her distinct personality, to Jee Kwak and the smile that never leaves his face, to Dr. John Day and Dr. Gregory Price and their willingness to help me in the lab, and to my childhood best friend and cousin, Rami Valari Spasov who always reminded me to take care of myself and respect my needs when I was totally ignoring them. Finally, this work could not be completed without the support of my family, especially my father who taught me how to be determined, patient and to pursue my goals no matter what. To my precious mom who stayed with me for almost a year and took care of my daughter Celina, the love of my life; to my wise and forgiving brother Houssam, to my sophisticated, prestigious brother Hassan and to my youngest brother Ghaleb who taught me how to love myself and live life to the maximum, to the wise woman, my sister in law Kate Brooks-Khadra. Thank you for all your support, for enduring my unpredictable working hours and for being understandable for every time I was questioned about my graduating date. vi TABLE OF CONTENTS ABSTRACT……………….……………………………………....……………………………...ii DEDICATION…....……………………………………………..…………………………...…...iv ACKNOWLEDGEMENTS………………………………………..……………………….….…v TABLE OF CONTENTS…………………………………………………………………..……vii LIST OF TABLES…………………………………………………..……….…………………...x LIST OF FIGURES…………………………………………………..…….……………….…....xi LIST OF SCHEMES…………………………………………….……….….……………….…xiii LIST OF ABBREVIATIONS……………………………………………..……….………..…xvii PUBLICATIONS………………………………………………………………………………..xx PART I: PALLADIUM-PEPPSI-IPENTCl; A USEFUL CATALYST FOR CHALLENGING AMINATION REACTIONS CHAPTER 1-Introduction………………………….…….……………………….………….....1 1.1 Significance of Aniline Derivatives…………………………....……….…………………..…1 1.2 Synthesis of Aniline Derivatives………………………….……………….……………..…...3 1.2.1 Nucleophilic Aromatic Substitution…………………………….…….…………….….....3 1.2.2 Aniline Derivatives from Nitrobenzene.…..……………………..……………….….…...4 1.2.3 Aniline from Nitrobenzene and Grignard Reagents……..……………….…………....….5 1.3 Metal-Catalyzed Amination Reactions……………………………………….………….........9 1.3.1 Copper-Catalyzed C-N Bond Formation………………...…..............................................9 1.3.2 Palladium-Catalyzed C-N Bond Formation……………………..…………………….....12 1.3.2.1 Mechanism of Buchwald-Hartwig Amination……………………………….......13 1.4 Ligand Development in Palladium-Catalyzed Buchwald-Hartwig Amination………………………..…………………………………………...…………….……16 1.4.1 Phosphine Ligands……………….….…………………………………………………...17 1.4.1.1 Quantifying Electronic and Steric Properties of Phosphine Ligands………………….……………………………………………………...……………...17 1.4.1.2 Phosphine Ligands in Palladium-Catalyzed Amination…………………………..18 1.4.1.3 Deficiencies of Phosphine Ligands……………………..........................................27 vii 1.4.2 N-Heterocyclic Carbenes………………………………………………………….……..28 1.4.2.1 Steric Characteristics of NHC……………………………………….……….…..30 1.4.2.2 Electronic parameter of NHC Ligands…...…….......………………………..…...31 1.4.2.4 Pd-NHC Complexes in Buchwald Amination.…………………….……...….…..33 1.5 Challenges in C-N Bond Formation………..……………………………………………...…36 1.5.1 Synthesis of Sterically Hindered Aniline Derivatives……………………………….….36 1.5.2 Synthesis of 2-Aminopyridine Derivatives………………………………………….….39 1.6 Plan of study……...………………………………………………………………………..…43 1.6.1. Synthesis of Sterically Hindered Arylamines…..…………………….……………...…43 1.6.2 Synthesis of 2-Aminopyridine…….………………..…………………………….….…44 CHAPTER 2-Synthesis of Hindered Anilines…………………..…………….……………....45 2.1 Reaction Optimization……………………..………………….……………………………..45 2.2 Substrate Scope with Primary Amines…………………….…………………..…………….47 2.3 Substrate Scope with Secondary Amines…………………………….………………..…….48 2.4 Conclusion………………………………………………………...........................................52 CHAPTER 3-Reactions of 2-Aminopyridine in Cross-Coupling…………………...……….53 3.1 Catalyst Screening………………………………….………….…………………….………53 3.2 Coupling of Electron-Poor 2-Aminopyridines………………….…………………….……..56 3.3 Impact of the Size of the C6-Substituent on the Catalytic Cycle……………….…….……..57 3.4 Coupling of Cyano-Substituted-2-Aminopyridine……………………………………..……58 3.5 Poisoning Effect of the 2-Aminopyridine Coupled Product on Pd Catalyst…….…………..59 3.6
Load more

Recommended publications
  • Desperately Seeking for the Catalytic Species in Suzuki-Miyaura Reaction Amine Bourouina
    Desperately Seeking For The Catalytic Species In Suzuki-Miyaura Reaction Amine Bourouina To cite this version: Amine Bourouina. Desperately Seeking For The Catalytic Species In Suzuki-Miyaura Reaction. Chemical and Process Engineering. Université de Lyon, 2019. English. NNT : 2019LYSE1258. tel-02482607 HAL Id: tel-02482607 https://tel.archives-ouvertes.fr/tel-02482607 Submitted on 18 Feb 2020 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. N°d’ordre NNT : 2019LYSE1258 THESE de DOCTORAT DE L’UNIVERSITE DE LYON opérée au sein de l’Université Claude Bernard Lyon 1 Ecole Doctorale ED206 Ecole Doctorale de Chimie de Lyon Spécialité de doctorat : Discipline : Procédés Soutenue publiquement le 28/11/2019, par : Amine BOUROUINA Desperately Seeking For The Catalytic Species In Suzuki-Miyaura Reaction Devant le jury composé de : FERRIGNO Rosaria, Professeure des Universités, Université Lyon Présidente HII King Kuok (Mimi), Professeure, L'Imperial College de Londres Rapporteuse RIANT Olivier, Professeur ordinaire, Université Catholique de Louvain Rapporteur
    [Show full text]
  • Novel Reagents and Catalysts for Facilitating Synthesis Peppsi™: A
    NOVELPEppSI ™REAGE: A NENWTS GE ANNERATIOD CATALYSTSN OF AIR FOR-STA FABCLEILITATI Pd PNRECG SATALYSTSYNTHESIS VOL. 39,38, NO.NO.1 4 •• 20062005 ROM Polymerization in Facilitated Synthesis Pd–N-Heterocyclic CarbenePolyurea-Encapsulated (NHC) Catalysts for Cross-CouplingPalladium ReactionsCatalysts sigma-aldrich.com New Products from Aldrich R&D BD3–THF Solution Stabilized with NIMBA and Alkynylboronates Me-CBS Solutions in THF Alkynylboronates participate in a variety of regio- and stereoselective The asymmetric borane reduction of prochiral ketones catalyzed by (R)- carbon–carbon bond-forming reactions including enyne cross metathesis 1 2 3 or (S)-Me-CBS provides a facile method for accessing chiral secondary (CM), Alder-ene, and Dötz annulation reactions. Products obtained alcohols.1 We are pleased to introduce N-isopropyl-N-methyl-tert-butylamine from these reactions are either alkenyl or arylboronates, which are active coupling partners in (NIMBA) stabilized BD3–THF solutions for the preparation of isotopically 2 Suzuki and Heck CH3 labeled alcohols. Amine-stabilized borane–THF solutions exhibit enhanced BPin O CH3 shelf-life over those containing other stabilizers, and additionally, higher reactions. BPin = B R 3 O CH3 levels of enantiomeric excess are obtained. Deuterium-labeled alcohols CH3 may also be synthesized through (1) Kim, M.; Lee, D. O HO D the sequence of hydroboration– OBD3 Org. Lett. 2005, 7, CH3 CH3 1865. (2) (a) Hansen, R' R' Cr(CO) oxidation of olefins. Either method (R)-Me-CBS 5 R R E. C.; Lee, D. J. Am. H3CO [Ru]+ of alcohol preparation gives high Chem. Soc. 2005, 127, [Ru] levels of deuterium incorporation R Yield (%) ee (%)D atom % 3252.
    [Show full text]
  • Umicore CX Catalysts Palladium Catalyzed Cross-Coupling Reactions 2 3
    Umicore CX Catalysts Palladium catalyzed cross-coupling reactions 2 3 Specific, well-defined precatalysts and ready-made catalysts UMICORE PMC WILL ASSIST YOU WITH OUR EXPERTISE IN ACTIVITY EXACTLY AS FAR AS IT IS NEEDED TO MEET YOUR NEEDS Palladium catalyzed C-C- and C-X bond forming reactions have undergone remarkable developments in the last 25 years [1]. Numerous research groups, inspired by the 2010 Chemistry Nobel Prize awardees Heck, Negishi and Suzuki [2], have developed new palladium precursors, ligands and catalysts to fully utilize this versatile, synthetic tool in organic chemistry. Some of these palladium complexes have transitioned into a broad range of applications spanning from synthesis of agrochemicals, use in natural products and active pharmaceutical ingredients down to appearing in materials for electronic applications. Umicore CX catalysts at glance: • Alternative Palladium precursors • Well-defined, ready-to-use Palladium phosphine complexes • Selective & active Palladium N-heterocyclic carbene complexes • Efficient Palladium recovery streams [1] a) Handbook of Organopalladium Chemistry for Organic Synthesis, (Eds.: E. Negishi, F. Diederich) Wiley-VCH, 2002, b) Metal-Catalyzed Cross Coupling Reactions, (Eds.: A. de Meijere, F. Diederich) Wiley-VCH, 2004, c) Angew. Chem. Int. Ed. 2012, 51, 5062 [2] http://www.nobelprize.org/nobel_prizes/chemistry/laureates/2010/popular-chemistryprize2010.pdf 4 5 CROSS-COUPLING REACTIONS ARE A TRANSITION METAL CATALYZED COUPLING OF AN ORGANIC ELECTROPHILE (I.E. ORGANIC HALIDE) WITH
    [Show full text]
  • Functionalized Nitrogen Ligands (CN) for Palladium Catalyzed Cross
    Journal of Organometallic Chemistry 881 (2019) 79e129 Contents lists available at ScienceDirect Journal of Organometallic Chemistry journal homepage: www.elsevier.com/locate/jorganchem Review Functionalized nitrogen ligands (CeN) for palladium catalyzed cross- coupling reactions (part II) Arjun Kumbhar Department of Chemistry, Padmabhushan Dr. Vasantraodada Patil College, Tasgaon, Affiliated to Shivaji University, Kolhapur, Maharashtra, 416312, India article info abstract Article history: In recent years, considerable effort has been focused in Pd catalyzed cross-coupling reactions, especially Received 6 April 2018 the use of less reactive and economically viable substrates like aryl chlorides. Unfortunately, Pd com- Received in revised form plexes containing the ligands having only N as a donor atom has some limitations, as it couples, mostly 22 September 2018 aryl iodides and bromides with different nucleophiles, and shows less activity towards aryl chlorides. Accepted 24 September 2018 This restriction can overwhelm by the use of Pd complexes containing N in combination with the C as a Available online 3 October 2018 donor atom such as palladacycles, pincers, PEPPSI and carbene ligands. The advantages of these ligands include high activity with enhanced selectivity, less toxicity, moisture, air as well as thermal stability. Keywords: Palladium Most importantly, such complexes have broad applications in catalysis under ambient conditions. This e Nitrogen ligands part of compressive review highlights the results of the highly active C N based Pd complexes and their NeC complexes applications in cross-coupling reactions. In the next part, we will cover all ligands and complexes con- Cross-couplings taining N in combination with P, O and S as a donor atoms (Pd catalysts based on CeP, CeO and CeS ligands).
    [Show full text]
  • Investigation of PEPPSI Precatalysts for Controlled Polymerization of Π-Conjugated Polymers from Cheap Starting Materials
    Investigation of PEPPSI precatalysts for controlled polymerization of π-conjugated polymers from cheap starting materials Thesis submitted in partial fulfilment of the requirement for a degree of Doctor of Philosophy at the University of London Benjamin John Groombridge Page | 1 Acknowledgements I would firstly like to thank my supervisors, Dr. Igor Larrosa and Dr. Stephen M. Goldup, for giving me the opportunity to carry out the research described in this thesis. Special gratitude to both of you, for the invaluable expert guidance and support during my PhD. I would like to thank the following people for the words of wisdom and practical input during the course of my PhD: Prof. Mike Watkinson, Dr. Chris Bray, Dr. Joby Winn, Dr. Jamie Lewis, Dr. Catherine Fletcher, Dr. Saidul Islam, Dr. Xacobe Couso Cambeiro, Dr. Nanna Ahlsten, Dr. Paolo Ricci, Dr. Carlos Arróniz, Dr. Sara Preciado, Dr. Francisco Juliá-Hernández, Dr. Josep Cornella, Dr. Tanya Boorman, Dr. Saidul Islam, Robert Bordoli, Ed Neal, Jessica Pancholi, Katrina Krämer, Rachel Grainger, Marco Simonetti, Junfei Luo, Adam Johnston, Gregory Perry and Nicky Willis. The research described would not have been possible without the fantastic support from both NMR and analytic services in particular Dr. Harold Toms and Dr. Ian Sanders. Finally, I would like to thank my friends and family for their support and advice throughout my PhD and during the writing up period. Page | 2 Declaration I declare that the scientific work presented in this thesis is my own and was carried out in the School of Biological and Chemical Science at Queen Mary, University of London between September 2010 and September 2014.
    [Show full text]
  • APPLICATION of Pd-NHC COMPLEXES in CHALLENGING
    APPLICATION OF Pd-NHC COMPLEXES IN CHALLENGING AMINATION REACTIONS SEPIDEH SHARIF A DISSERTATION SUBMITTED TO THE FACULTY OF GRADUATE STUDIES IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY GRADUATE PROGRAM IN CHEMISTRY YORK UNIVERSITY TORONOTO, ONTARIO FEBRUARY 2019 © SEPIDEH SHARIF 2019 ABSTRACT Among Pd-catalyzed carbon-heteroatom cross-coupling reactions, C-N bond formation, known as Buchwald-Hartwig amination (BHA), is by far the most studied reaction owing to the prevalence of arylated amines in pharmaceuticals, natural products, organic materials, and catalysts. Despite the tremendous progress that has been achieved with respect to improving the efficiency and expanding the scope of BHA of (hetero)aryl halides and amine nucleophilic partners, some challenges remain to be addressed. These challenges include selective monoarylation of primary alkyl amines, enantioretentive N-arylation of a-amino esters and arylation of amide nucleophiles. This research is mainly focused on evaluating the reactivity of Pd-NHC pre-catalysts, in particular Pd-PEPPSI (Pyridine Enhanced Pre-catalyst Preparation Stabilization and Initiation) complexes in such challenging BHA reactions. Pd-PEPPSI-IPentCI, was identified as one of the most reactive and selective pre-catalysts yet reported in the literature in the arylation of primary alkyl amines. The high level of selectivity that was exhibited by Pd-PEPPSI-IPentCI is assured by the use of the mild, soluble and sterically demanding sodium salt of butylated hydroxytoluene (NaBHT) as the base in this transformation. Pd-PEPPSI-IPentCl-o-picoline was shown to effectively couple a variety of amino acids as the tert-butyl ester with heteroaryl chlorides in high yields and with excellent stereoretention of the acidic proton adjacent to the ester.
    [Show full text]
  • Cross Coupling Reactions Catalyzed by (NHC)Pd(II) Complexes
    Turkish Journal of Chemistry Turk J Chem (2015) 39: 1115 { 1157 http://journals.tubitak.gov.tr/chem/ ⃝c TUB¨ ITAK_ Review Article doi:10.3906/kim-1510-31 Cross coupling reactions catalyzed by (NHC)Pd(II) complexes Nevin GURB¨ UZ¨ 1, Emine Ozge¨ KARACA1, Ismail_ OZDEM¨ IR_ 1;∗, Bekir C¸ETINKAYA_ 2;∗ 1Catalysis Research and Application Center, In¨on¨uUniversity,_ Malatya, Turkey 2Department of Chemistry, Ege University, Bornova, Izmir,_ Turkey Received: 13.10.2015 • Accepted/Published Online: 17.11.2015 • Printed: 25.12.2015 Abstract: This review is focused on new developments reported during the last 3 years concerning the catalytic performances of in situ formed or preformed NHC{Pd(II) complexes (NHC: N -heterocyclic carbene) for cross-coupling reactions such as Heck{Mizoraki (often shortened to the Heck reaction), Kumada, Negishi, Suzuki{Miyaura (often shortened to the Suzuki reaction), Sonogashira and Hiyama couplings, and the Buchwald{Hartwig aminations, which are extremely powerful in the formation of C{C and C{heteroatom bonds. Due to the great number of publications and limited space here, we made a special attempt to compile the relevant data in tables, which we hope will serve as a guide for chemists interested in these reactions. The syntheses of the precatalysts and the generally accepted reaction mechanisms are also briefly described. Key words: N -heterocyclic carbene, palladium, cross-coupling reaction 1. Introduction The awarding of the 2010 Nobel Prize jointly to Heck, Suzuki, and Negishi clearly reflects the importance of palladium-catalyzed cross-coupling reactions in chemistry. 1 They provide chemists with a very versatile tool for the construction of carbon{carbon and carbon{heteroatom bonds in the synthesis of pharmaceuticals, agrochemicals, and organic electronic materials.
    [Show full text]
  • Complex and Its Efficiency As a Catalyst for Mizoroki-Heck Cross-Coupling
    J. Chem. Sci. Ó (2020) 132:51 Indian Academy of Sciences https://doi.org/10.1007/s12039-020-1754-y Sadhana(0123456789().,-volV)FT3](0123456789().,-volV) REGULAR ARTICLE A new PEPPSI type N-heterocyclic carbene palladium(II) complex and its efficiency as a catalyst for Mizoroki-Heck cross-coupling reactions in water DHRUBAJIT BORAHa,b , BISWAJIT SAHAc,d , BIPUL SARMAe and PANKAJ DASa,* aDepartment of Chemistry, Dibrugarh University, Dibrugarh, Assam 786004, India bDepartment of Chemistry, N. N. Saikia College, Titabar, Assam 785630, India cAdvanced Materials Group, Materials Sciences and Technology Division, CSIR-North East Institute of Science and Technology, Jorhat, Assam 785006, India dAcademy of Scientific and Innovative Research (AcSIR), CSIR-NEIST Campus, Jorhat, Assam 785006, India eDepartment of Chemical Sciences, Tezpur University, Napaam, Tezpur, Assam 784028, India E-mail: [email protected] MS received 29 August 2019; revised 7 November 2019; accepted 10 November 2019 Abstract. A new air and moisture stable PEPPSI (PEPPSI: pyridine-enhanced pre-catalyst preparation, stabilisation, and initiation) themed palladium N-heterocyclic carbene (NHC) complex [Pd(L)Br2(Py)] (1) [L: 2-flurobenzyl)-1-(4-methoxyphenyl)-1H-imidazolline-2-ylidene] was synthesized and characterized. The structure of complex 1 was determined by X-ray single-crystal analysis. The palladium center in 1 adopted a square planar geometry with carbene and pyridine ligands occupying the mutual trans position. The complex 1 was employed to catalyze the Mizoroki-Heck cross-coupling reactions of aryl bromides/iodides with styrene in water. To the best of our knowledge, this is the first report where a Pd-PEPPSI catalyst was successfully employed in aqueous-phase Mizoroki-Heck reaction.
    [Show full text]
  • Enhanced Precatalyst Preparation Stabilization and Initiation (EPPSI) Nano Molecules
    Opinion Metabolomics: Volume 11:1, 2021 Open Access ISSN: 2153-0769 Open Access Putrescine, Cadaverine, Spermine and Spermidine- Enhanced Precatalyst Preparation Stabilization and Initiation (EPPSI) Nano Molecules Ricardo Gobato1, Alireza Heidari2* 1Green Land Landscaping and Gardening, Seedling Growth Laboratory, 86130-000, Parana, Brazil 2Faculty of Chemistry, California South University, 14731 Comet St. Irvine, CA 92604, USA Keywords: Putrescine • Cadaverine • Spermine Opinion relatively easy to synthesize and handle.In this work, the term Enhanced Precatalyst Preparation Stabilization and Initiation (EPPSI) is used.In the basic structure of PEPPSI, R can be a methyl (CH , Me), ethyl (C H , Et), In the current study, we study Putrescine, Cadaverine, Spermine and 3 2 5 isopropyl (C H , iPr), isopentyl (C H , iPent), or isoheptyl (C H , iHept) Spermidine–Enhanced Precatalyst Preparation Stabilization and Initiation 3 7 5 11 7 15 group, and the resulting catalysts are thus labeled as PEPPSI-IMes, (EPPSI) Nano molecules incorporation into the Nano Polymeric Matrix PEPPSI-IEt, PEPPSI-IPr, PEPPSI-IPent, and PEPPSI-IHept respectively, (NPM) by immersion of the Nano Polymeric Modified Electrode (NPME) with or without "Pd-" added in front. Contrary to common palladium-based as molecular enzymes and drug targets for human cancer cells, tissues catalysts, such as tetrakis(triphenylphosphine)palladium(0), PEPPSI is and tumors treatment under synchrotron and synchrocyclotron radiations. stable to exposure to air and moisture. Even heating in dimethyl sulfoxide at Putrescine is related to cadaverine (both polyamine). Both are produced 120°C for hours does not result in significant decomposition or neutralization by the breakdown of amino acids in living and dead organisms and both of PEPPSI catalysts.
    [Show full text]
  • Aminomethylpyridinequinones As New Ligands for PEPPSI-Type Complexes
    The Free Internet Journal Paper for Organic Chemistry Archive for Arkivoc 2021, part iii, 0-0 Organic Chemistry to be inserted by editorial office Aminomethylpyridinequinones as new ligands for PEPPSI-type complexes Roman Gajda,a Albert Poater,b Artur Brotons-Rufes,b Sebastian Planer,a Krzysztof Woźniak,a Karol Grela,a and Anna Kajetanowicza,c,* a Biological and Chemical Research Centre, Faculty of Chemistry, University of Warsaw, Żwirki i Wigury 101, 02-089 Warsaw, Poland b Institut de Química Computacional i Catàlisi, Departament de Química, University of Girona, c/ Maria Aurèlia Capmany 69, Girona 17003, Catalonia, Spain c Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland Email: [email protected] Dedicated to Professor Lanny Liebeskind Received mm-dd-yyyy Accepted mm-dd-yyyy Published on line mm-dd-yyyy Dates to be inserted by editorial office Abstract A set of six new catalysts possessing quinone moieties in a pyridine ligand was synthesized and fully characterized by standard analytical techniques, including X-Ray crystallography. The results obtained in Suzuki and Mizoroki–Heck cross-coupling reactions catalyzed by quinone-based compounds were comparable to these obtained in the presence of the original PEPPSI complex designed by Organ. DFT calculations allow us to see the structural and electronic factors to describe their similarity. On the other hand, steric maps and NCI plots were the tools to have a more global view of the systems studied, leaving the sphere of reactivity around the metal. Keywords: Cross-coupling, PEPPSI, pyridine, quinones, NHC DOI: https://doi.org/10.24820/ark.5550190.p011.451 Page 1 ©AUTHOR(S) Arkivoc 2021, iii, 0-0 Gajda, R.
    [Show full text]
  • Uppsala University
    Uppsala University Project Thesis Suzuki coupling of functionalized arylboronic acids to a 2-Amino-5-(4-bromophenyl)-1,3,4-thiadiazole scaffold Supervisors: Author: Dr. Wei Berts Fredric Ingner Dr. Jonas Malmström February 21, 2015 Abstract Seven arylboronic acids, all but one containing functional groups, were cho- sen for Suzuki cross coupling to a predetermined scaffold for a contract project. The scaffold was synthesized and catalytic ability was assesed for three palla- dium catalysts: Tetrakis(triphenylphosphine)palladium(0) (Pd(PPh3)4), (1,1’- Bis(diphenylphosphino)ferrocene)palladium(II) dichloride (Pd(DPPF)Cl2) and PEPPSI-iPr. Library reactions proceeded with Tetrakis since it was found to be the only catalyst capable of producing product during trials. All reactions were worked up by flash chromatography, except one where preperative HPLC had to be used. Reactions and purification steps were analyzed crudely with TLC and more thoroughly through LC-MS with ESI. Structural analysis in form of 1H-NMR was made of the scaffold and two products. It was found that all but one of the seven reactions proceeded to completion with 0.1 eq of catalyst under alkali conditions at 80o C. 1 Acknowledgements I would like to thank Dr. Fredrik Lehmann for allowing me to do my thesis work at OnTarget Chemistry. I am very grateful to have been supervised by Dr. Wei Berts and Dr. Jonas Malmström, without whom this thesis would not have been possible. I also extend my gratitude to all of the employees of OnTarget Chemistry who have made me feel very much at home and as a part of the team.
    [Show full text]
  • Catalysis PEPPSI™ Catalyst
    Vol. 6 No. 3 Catalysis PEPPSI™ Catalyst General Background Advantages of PEPPSI™ Reaction Types · Negishi · Suzuki · Buchwald–Hartwig · Kumada Future Generation PEPPSI™ sigma-aldrich.com General Background Palladium has played a central role in the expeditious preparation of complex organic Vol. 6 No. 3 molecules, since the discovery and subsequent catalytic use of Pd(PPh3)4 by Malatesta, Angoletta and others.1 In the world of catalysis, the ancillary ligands of any Pd complex represent the chassis, whereas the Pd center functions as the driver for cross-coupling Aldrich Chemical Co., Inc. reactions. These metal-catalyzed processes arguably remain the most powerful means Sigma-Aldrich Corporation to generate C–C, C–O, and C–N bonds in the synthetic chemist’s toolbox.2,3 Catalyst 6000 N. Teutonia Ave. developments in the cross-coupling field have been concentrated in rapid design and deployment of complexes containing tertiary phosphine ligands. The disadvantages of Milwaukee, WI 53209, USA utilizing phosphines as ligands for Pd are numerous, including their high expense, sensitivity, and lack of commercial sources for late generation compounds. Perhaps most importantly, few catalysts exhibit superior activity among broad substrate classes and reaction paradigms. To Place Orders It should also be noted that Pd(PPh3)4 is widely applied in catalysis, but this complex suffers Telephone 800-325-3010 (USA) from poor stability upon storage as well as advised handling under nitrogen. FAX 800-325-5052 (USA) N-Heterocyclic carbene (NHC) Pd complexes have been designed in order to overcome some of these limitations.4 Professor Mike Organ at York University, along with co- Customer & Technical Services workers Dr.
    [Show full text]