Development of Novel Synthetic Approaches in Nickel-catalyzed Cross-coupling Reactions
Author: Takashi Tomioka
Publisher:
Published: 2004
Total Pages: 0
ISBN-13:
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Development of Nickel-catalyzed Stereospecific Cross-coupling Reactions
Author: Buck L. H. Taylor
Publisher:
Published: 2012
Total Pages: 171
ISBN-13: 9781267652379
DOWNLOAD EBOOKTransition-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.
Development of Nickel-Catalyzed Cross-Coupling Reactions
Author: Liana Hie
Publisher:
Published: 2016
Total Pages: 620
ISBN-13:
DOWNLOAD EBOOKTransition 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
Author: Yoshinao Tamaru
Publisher: John Wiley & Sons
Published: 2006-03-06
Total Pages: 346
ISBN-13: 3527604235
DOWNLOAD EBOOKOrganonickel 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.
Nickel Catalysis in Organic Synthesis
Author: Sensuke Ogoshi
Publisher: John Wiley & Sons
Published: 2020-03-09
Total Pages: 348
ISBN-13: 3527344071
DOWNLOAD EBOOKA 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 Novel Cross-Coupling Reactions Via Nickel-Catalyzed C-O/C-N Bond Activation and Nickel/Photoredox Dual Catalysis
Author: Huifeng Yue
Publisher:
Published: 2018
Total Pages: 128
ISBN-13:
DOWNLOAD EBOOKDevelopment of Nickel-Catalyzed Coupling Reactions
Author: Mikhail Olegovich Konev
Publisher:
Published: 2017
Total Pages: 503
ISBN-13: 9780355308976
DOWNLOAD EBOOKTransition 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.
The Development of New Catalytic Reactions
Author: Adisak Chatupheeraphat
Publisher:
Published: 2018
Total Pages:
ISBN-13:
DOWNLOAD EBOOKDevelopment of Stereospecific Nickel-Catalyzed Cross-Coupling Reactions
Author: Emily Jean Tollefson
Publisher:
Published: 2016
Total Pages: 575
ISBN-13: 9781369226966
DOWNLOAD EBOOKThe development of asymmetric transition-metal-catalyzed reactions has emerged as an important area of research in the past decade. Advances in the field are transforming the way chemists approach the construction of target compounds. This dissertation focuses on the expansion of stereospecific nickel-catalyzed reactions to synthesize small unnatural polyketide analogs, chiral long chain carboxylic acids, and highly substituted cyclopropanes. In the presence of an achiral nickel catalyst, a bidentate phosphine ligand, and a Grignard reagent, aryl-substituted tetrahydropyrans and tetrahydrofurans undergo a stereospecific ring-opening to afford acyclic polyketide analogs with complex stereoarrays and promising anti-cancer activity. Reactions proceed with inversion of stereochemistry at the benzylic position and are substrate controlled. Similarly, enantioenriched aryl-substituted lactones undergo a Negishi-type cross-coupling with dimethylzinc to afford enantioenriched carboxylic acids. The utility of this reaction was demonstrated in a two-step synthesis of an anti-dyslipidemia agent.The nickel catalyst system was employed to develop the first stereospecific reductive cross-coupling reaction. 2-Aryl-4-chlorotetrahydropyrans undergo an intramolecular ring contraction to afford highly substituted cyclopropanes. The reactions proceed with retention at the benzylic center and inversion at the alkyl halide position. Vinyl-substituted tetrahydropyrans are also amenable substrates for this transformation and afford vinylcyclopropane products with excellent control of stereochemistry. This is the first reported reductive coupling between alkyl ethers and alkyl halides and provides a new, mild synthetic route to both aryl- and vinyl-substituted cyclopropanes.
Development of Stereospecific Nickel-Catalyzed Cross-Coupling and Reductive Cross-Electrophile Coupling Reactions
Author: Lucas William Erickson
Publisher:
Published: 2017
Total Pages: 321
ISBN-13: 9780355307122
DOWNLOAD EBOOKIn recent years, the Jarvo lab has developed the field of stereospecific nickel-catalyzed cross-coupling reactions of benzylic electrophiles. This chemistry allows for straightforward synthesis of asymmetric C--C bonds. The focus of this dissertation is on the study of the mechanism of these transformations, and the development of reductive cross-electrophile coupling reactions.First, the mechanism of the nickel-catalyzed Kumada cross-coupling reaction was studied via a 13C kinetic isotope effect experiment. This experiment indicated that oxidative addition of the nickel catalyst into the C--O sigma bond was the rate limiting step. Combining this data with a rate law allowed us to propose a catalytic cycle for this reaction. Additionally, the nickel-catalyzed deoxygenation of benzylic ethers was optimized for the formation of diaryl methanes. Deoxygenation performed best with a proton-rich Grignard reagent. We demonstrated that these Grignard reagents act as the hydride source for the reduction reaction.Next, an intramolecular nickel-catalyzed reductive cross-electrophile coupling reaction of benzylic ethers and alkyl chlorides was developed. This reaction proceeds with a variety of extended aromatic and heteroaromatic groups to produce cyclopropane rings in great yields and diastereoselectivity. This is the first example of a stereospecific reductive cross-electrophile coupling reaction, as well as the first to employ alkyl ethers and alkyl halides as the electrophiles.Finally, the work on nickel-catalyzed reductive cross-electrophile coupling reactions was expanded to synthesize vinylcyclopropanes from allylic ethers and alkyl halides. This reaction occurs with both alkyl fluorides and alkyl chlorides. To the best of our knowledge, this is the first reported cross-electrophile coupling reaction of an alkyl fluoride. Ring contraction proceeds with high stereospecificity, providing selective synthesis of either diastereomer of di- and tri-substituted cyclopropanes. The utility of this methodology is demonstrated by several synthetic applications including the synthesis of the natural product dictyopterene A. 2-Vinyl-4-fluorotetrahydrofurans also undergo stereospecific ring contractions, providing access to synthetically useful hydroxymethyl cyclopropanes.
