Development of Nickel-catalyzed Stereospecific Cross-coupling Reactions
Development of Nickel-catalyzed Stereospecific Cross-coupling Reactions

Author: Buck L. H. Taylor

Publisher:

Published: 2012

Total Pages: 171

ISBN-13: 9781267652379

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Transition-metal catalyzed cross-coupling reactions are powerful methods for the synthesis of natural products and medicinal compounds. Cross-coupling reactions of secondary alkyl electrophiles are currently more challenging than those of aryl or vinyl halides, but these reactions enable the construction of tertiary stereogenic centers with control of configuration. Several methods have been reported for the stereoconvergent cross-coupling of alkyl halides using chiral nickel catalysts. Herein, we report the development of a stereospecific cross-coupling reaction of enantioenriched benzylic ethers using achiral nickel catalysts. We initially performed mechanistic studies to determine the stereochemical course of established nickel-catalyzed cross-coupling reactions. A deuterium-labeled alkylborane reagent was used to establish that transmetalation from boron to nickel occurs with retention of configuration. In addition, these studies establish that alkylnickel intermediates are stereochemically stable under these cross-coupling conditions. A stereospecific cross-coupling reaction of benzylic ethers with alkyl Grignard reagents has been developed. Enantioenriched benzylic ethers, derivatives of easily synthesized chiral secondary alcohols, undergo cross-coupling with high enantiospecificity using an achiral nickel catalyst. The method was applied to the asymmetric synthesis of a biologically active diarylethane, a common structural motif in medicinally relevant compounds. Initial mechanistic studies are consistent with a rate-limiting oxidative addition that is facilitated by a magnesium Lewis-acid. The cross-coupling method has been extended to include aryl Grignard reagents for the asymmetric synthesis of triarylmethanes. The reaction proceeds in high enantiospecificity and employs an ether leaving group capable of chelating to magnesium ions. The method was applied to the asymmetric synthesis of an anti-breast-cancer agent.

Nickel Catalysis in Organic Synthesis
Nickel Catalysis in Organic Synthesis

Author: Sensuke Ogoshi

Publisher: John Wiley & Sons

Published: 2020-03-09

Total Pages: 348

ISBN-13: 3527344071

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A comprehensive reference to nickel chemistry for every scientist working with organometallic catalysts Written by one of the world?s leading reseachers in the field, Nickel Catalysis in Organic Synthesis presents a comprehensive review of the high potential of modern nickel catalysis and its application in synthesis. Structured in a clear and assessible manner, the book offers a collection of various reaction types, such as cross-coupling reactions, reactions for the activation of unreactive bonds, carbon dioxide fixation, and many more. Nickel has been recognized as one of the most interesting transition metals for homogeneous catalysis. This book offers an overview to the recently developed new ligands, new reaction conditions, and new apparatus to control the reactivity of nickel catalysts, allowing scientists to apply nickel catalysts to a variety of bond-forming reactions. A must-read for anyone working with organometallic compounds and their application in organic synthesis, this important guide: -Reviews the numerous applications of nickel catalysis in synthesis -Explores the use of nickel as a relatively cheap and earth-abundant metal -Examines the versatility of nickel catalysis in reactions like cross-coupling reactions and CH activations -Offers a resource for academics and industry professionals Written for catalytic chemists, organic chemists, inorganic chemists, structural chemists, and chemists in industry, Nickel Catalysis in Organic Synthesis provides a much-needed overview of the most recent developments in modern nickel catalysis and its application in synthesis.

Development of Nickel-Catalyzed Coupling Reactions
Development of Nickel-Catalyzed Coupling Reactions

Author: Mikhail Olegovich Konev

Publisher:

Published: 2017

Total Pages: 503

ISBN-13: 9780355308976

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Transition metal catalyzed reactions are ubiquitous in the realm of synthetic chemistry, allowing for the strategic construction of complex molecular frameworks of pharmaceuticals, natural products, and synthetic materials. Palladium-catalyzed cross-coupling reactions are part of the foundation of these transformations, insofar as they were recognized with the 2010 Nobel Prize in chemistry. Traditionally, these reactions have relied on aryl and vinyl electrophiles, whereas the alkyl counterparts have only recently begun to emerge in the literature. Nickel has been on the forefront of enantioconvergent alkyl cross--coupling reactions due to its propensity to undergo single electron chemistry. However, under special conditions, it has a unique ability to break strong carbon--oxygen bonds in a stereospecific manner, making research into its reactivity a valuable endeavor to the field of organometallic chemistry.Chapter 1 describes the development of a stereospecific intramolecular alkyl-Heck cyclization of benzylic ethers. The reaction proceeds with inversion at the electrophilic carbon, for the synthesis of methylenecyclopentanes of both extended pi-electron and simple aromatic systems. The enantioenriched products can be effectively derivatized to cyclic alpha-aryl ketones in good yields with good transfer of chirality. Avenues to expand the utility of this reaction have been identified and further studies are ongoing.Chapter 2 discusses the development of nickel-catalyzed cross-electrophile coupling reactions of benzylic esters and aryl halides. An intermolecular reaction proceeds in high yields for primary benzylic esters for the synthesis of pharmacologically relevant diarylmethanes. The corresponding intramolecular cyclization proceeds under mild conditions, demonstrating the first example of a stereospecific cross-electrophile coupling of secondary benzylic esters. A variety of heterocyclic and functionalized substrates are tolerated under the reaction conditions.Chapter 3 examines the development a regio- and stereoselective nickel-catalyzed hydroarylation of alkynes with arylboronic acids. The reaction is facilitated by propargyl carbamates as directing groups. The reaction is tolerant of a range of functional groups and heterocycles. Mechanistic studies reveal that the acidic protons of the arylboronic acid coupling partner serve as the origin of hydrogen. Furthermore, the synthesis of tamoxifen can be completed in two steps from a simple hydroarylation product.

Development of Nickel-Catalyzed Cross-Coupling Reactions
Development of Nickel-Catalyzed Cross-Coupling Reactions

Author: Liana Hie

Publisher:

Published: 2016

Total Pages: 620

ISBN-13:

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Transition metal-catalyzed cross-couplings provide a powerful means to assemble carbon-carbon (C-C) and carbon-heteroatom (C-X) bonds. Although Pd catalysis is most commonly used in these transformations, Ni catalysis offers a valuable alternative due to the low cost and high reactivity of Ni. More importantly, Ni catalysis has proven effective for the activation of traditionally inert carbon-heteroatom bonds and therefore provides exciting opportunities with regard to chemical reactivity and synthetic applications. Chapter one, two, and three describe the development of practical cross-coupling methodologies. Chapter one explains the amination of aryl sulfamates and carbamates that relies on an air-stable Ni(II) precatalyst. Chapter two introduces the development of green cross-couplings of phenolic derivatives and aryl halides to form biaryls. Subsequently, the couplings of heterocycles, which are commonly encountered in natural product synthesis and in the pharmaceutical sector, are described. Chapter three describes the development of green cross-couplings of aryl sulfamates and chlorides to form aryl amines. Chapter four and seven concern the utility of amides as electrophilic cross-coupling partners. These traditionally unreactive moieties are activated by nickel and coupled to alcohols to form acyl C-O bonds. This study suggests that amides may serve as useful building blocks to construct carbon-carbon and carbon-heteroatom bonds. Chapter four describes the development of nickel-catalyzed activation of benzamides and chapter seven introduces the development of nickel-catalyzed activation of aliphatic amide derivatives. Chapter five describes the nickel-catalyzed activation of the acyl carbon-oxygen bonds of methyl esters through an oxidative addition process. The oxidative addition adducts, formed using nickel catalysis, undergo in situ trapping to provide anilide products. DFT calculations are used to support the proposed reaction mechanism, understand why decarbonylation does not occur competitively, and to elucidate the beneficial role of the substrate structure and Al(OtBu)3 additive on the kinetics and thermodynamics of the reaction. Chapter six focus on the nickel-catalyzed Heck cyclization for the construction of quaternary stereocenters. This transformation is demonstrated in the synthesis of 3,3-disubstituted oxindoles, which are prevalent motifs seen in bioactive molecules.

Modern Organonickel Chemistry
Modern Organonickel Chemistry

Author: Yoshinao Tamaru

Publisher: John Wiley & Sons

Published: 2006-03-06

Total Pages: 346

ISBN-13: 3527604235

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Organonickel chemistry plays an increasingly important role in organic chemistry, and interest in this topic is now just as keen as in organopalladium chemistry. While there are numerous, very successful books on the latter, a book specializing in organonickel chemistry is long overdue. Edited by one of the leading experts in the field, this volume covers the many discoveries made over the past 30 years, and previously scattered throughout the literature. Active researchers working at the forefront of organonickel chemistry provide a comprehensive review of the topic, including cross-coupling reactions, asymmetric synthesis and heterogeneous catalysis reaction types. A must-have for both organometallic chemists and synthetic organic chemists.

The Mizoroki-Heck Reaction
The Mizoroki-Heck Reaction

Author: Martin Oestreich

Publisher: John Wiley & Sons

Published: 2009-02-11

Total Pages: 608

ISBN-13: 9780470716069

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Exploring the importance of Richard F. Heck’s carbon coupling reaction, this book highlights the subject of the 2010 Nobel Prize in Chemistry for palladium-catalyzed cross couplings in organic synthesis, and includes a foreword from Nobel Prize winner Richard F. Heck. The Mizoroki-Heck reaction is a palladium-catalyzed carbon–carbon bond forming process which is widely used in organic and organometallic synthesis. It has seen increasing use in the past decade as chemists look for strategies enabling the controlled construction of complex carbon skeletons. The Mizoroki-Heck Reaction is the first dedicated volume on this important reaction, including topics on: mechanisms of the Mizoroki-Heck reaction intermolecular Mizoroki-Heck reactions focus on regioselectivity and product outcome in organic synthesis waste-minimized Mizoroki-Heck reactions intramolecular Mizoroki-Heck reactions formation of heterocycles chelation-controlled Mizoroki-Heck reactions the Mizoroki-Heck reaction in domino processes oxidative heck-type reactions (Fujiwara-Moritani reactions) Mizoroki-Heck reactions with metals other than palladium ligand design for intermolecular asymmetric Mizoroki-Heck reactions intramolecular enantioselective Mizoroki-Heck reactions desymmetrizing Mizoroki-Heck reactions applications in combinatorial and solid phase syntheses, and the development of modern solvent systems and reaction techniques the asymmetric intramolecular Mizoroki-Heck reaction in natural product total synthesis Several chapters are devoted to asymmetric Heck reactions with particular focus on the construction of otherwise difficult-to-obtain sterically congested tertiary and quaternary carbons. Industrial and academic applications are highlighted in the final section. The Mizoroki-Heck Reaction will find a place on the bookshelves of any organic or organometallic chemist. “I am convinced that this book will rapidly become the most important reference text for research chemists in academia and industry who seek orientation in the rapidly growing and – for the layman – confusing field described as the “’Mizoroki–Heck reaction’.” (Synthesis, March 2010)

Ni- and Fe-Based Cross-Coupling Reactions
Ni- and Fe-Based Cross-Coupling Reactions

Author: Arkaitz Correa

Publisher: Springer

Published: 2016-11-26

Total Pages: 342

ISBN-13: 3319497847

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The series Topics in Current Chemistry Collections presents critical reviews from the journal Topics in Current Chemistry organized in topical volumes. The scope of coverage is all areas of chemical science including the interfaces with related disciplines such as biology, medicine and materials science. The goal of each thematic volume is to give the non-specialist reader, whether in academia or industry, a comprehensive insight into an area where new research is emerging which is of interest to a larger scientific audience. Each review within the volume critically surveys one aspect of that topic and places it within the context of the volume as a whole. The most significant developments of the last 5 to 10 years are presented using selected examples to illustrate the principles discussed. The coverage is not intended to be an exhaustive summary of the field or include large quantities of data, but should rather be conceptual, concentrating on the methodological thinking that will allow the non-specialist reader to understand the information presented. Contributions also offer an outlook on potential future developments in the field.

Nickel- and Palladium-Catalyzed Cross Coupling Reactions
Nickel- and Palladium-Catalyzed Cross Coupling Reactions

Author: Rebecca Green

Publisher:

Published: 2016

Total Pages: 183

ISBN-13:

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The following dissertation discusses the development of a nickel catalyst for the synthesis of Csp2-Csp bonds in addition to the development and mechanistic studies of nickel and palladium catalysts for the synthesis of Csp2-N bonds. The first chapter is a review of the cross-coupling reactions discussed in this dissertation. Nickel and palladium will be compared with respect to physical properties and reactivity differences. The challenges associated with nickel-catalyzed cross coupling will be illustrated, while drawing analogies to analogous palladium-catalyzed reactions. The literature background for the synthesis of Csp2-Csp bonds, catalyzed by palladium and palladium/copper catalytic systems, will be reviewed, while highlighting the challenges and limitations of the field. The field of Csp2-N bond-forming reactions will be examined, as the differences in reactivity between nickel and palladium will be emphasized. Chapter 2 discusses our efforts towards the development of a nickel catalyst for the development of a Csp2-Csp bond forming reaction, performed in the absence of a copper co-catalyst. Chapter 3 describes the development of a single-component nickel complex that catalyzes the coupling of aryl chlorides with primary alkylamines. A series of mechanistic experiments, including synthesis of catalytic intermediates and kinetic experiments, were performed to elucidate the mechanism of the reaction. Chapter 4 discusses our report the palladium-catalyzed coupling of aryl halides withammonia and gaseous amines as their ammonium salts. A difference in selectivity between reactions of aryl chlorides and aryl bromides was discovered and investigated. Chapter 5 describes the development of a single-component nickel catalyst for the coupling of aryl chlorides with ammonia and ammonium sulfate to form the corresponding primary arylamines. The application of ammonium salts was extended to the coupling of gaseous amines, such as methylamine and ethylamine, which were subjected to the reaction conditions as their hydrochloride salt.