[PDF] Amide Bond Activation eBook

Author : Michal Szostak
Publisher : MDPI
Page : 466 pages
File Size : 30,57 MB
Release : 2019-07-12
Category : Science
ISBN : 3039212036

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The amide bond represents a privileged motif in chemistry. The recent years have witnessed an explosion of interest in the development of new chemical transformations of amides. These developments cover an impressive range of catalytic N–C bond activation in electrophilic, Lewis acid, radical, and nucleophilic reaction pathways, among other transformations. Equally relevant are structural and theoretical studies that provide the basis for chemoselective manipulation of amidic resonance. This monograph on amide bonds offers a broad survey of recent advances in activation of amides and addresses various approaches in the field.

Author : Michal Szostak
Publisher : John Wiley & Sons
Page : 533 pages
File Size : 31,30 MB
Release : 2022-10-10
Category : Science
ISBN : 352734831X

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Amide Bond Activation Comprehensive resource on the pivotal role of the amide bond in organic synthesis This book provides the reader with insight into the advances that have taken place in the field of amide bond activation. It focuses on both the fundamental structural properties of the amide bond and the synthetic reactions mediated by transition-metals. By discussing amide bond activation in terms of modern organic synthesis, the reader is provided with a thorough overview of the area and its crucial role in forging carbon-carbon and carbon-heteroatom bonds. Sample topics discussed within the work include: Cross-coupling of amides Amide bond activation by twisting and nitrogen pyramidalization Electrophilic amide bond functionalization Transition metal-catalyzed radical reactions of amides Amide bond esterification, hydrolysis and transamidation Classical bridged lactams and anomeric amides Computational studies of amide C-N bond activation Cross-coupling of esters by C-O activation The book is immensely valuable to synthetic chemists in academia and the pharmaceutical industry who wish to gain an in-depth understanding of the concept of amide bond activation.

Author : Michal Szostak
Publisher : John Wiley & Sons
Page : 533 pages
File Size : 38,98 MB
Release : 2022-10-18
Category : Science
ISBN : 352783026X

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Amide Bond Activation Comprehensive resource on the pivotal role of the amide bond in organic synthesis This book provides the reader with insight into the advances that have taken place in the field of amide bond activation. It focuses on both the fundamental structural properties of the amide bond and the synthetic reactions mediated by transition-metals. By discussing amide bond activation in terms of modern organic synthesis, the reader is provided with a thorough overview of the area and its crucial role in forging carbon-carbon and carbon-heteroatom bonds. Sample topics discussed within the work include: Cross-coupling of amides Amide bond activation by twisting and nitrogen pyramidalization Electrophilic amide bond functionalization Transition metal-catalyzed radical reactions of amides Amide bond esterification, hydrolysis and transamidation Classical bridged lactams and anomeric amides Computational studies of amide C-N bond activation Cross-coupling of esters by C-O activation The book is immensely valuable to synthetic chemists in academia and the pharmaceutical industry who wish to gain an in-depth understanding of the concept of amide bond activation.

Author : Michal Szostak
Publisher :
Page : 466 pages
File Size : 41,32 MB
Release : 2019
Category : Chemistry
ISBN : 9783039212040

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The amide bond represents a privileged motif in chemistry. The recent years have witnessed an explosion of interest in the development of new chemical transformations of amides. These developments cover an impressive range of catalytic N-C bond activation in electrophilic, Lewis acid, radical, and nucleophilic reaction pathways, among other transformations. Equally relevant are structural and theoretical studies that provide the basis for chemoselective manipulation of amidic resonance. This monograph on amide bonds offers a broad survey of recent advances in activation of amides and addresses various approaches in the field.

Author : Rachel Knapp
Publisher :
Page : 510 pages
File Size : 44,9 MB
Release : 2022
Category :
ISBN :

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This dissertation describes the development of reaction methodologies that utilize unconventional building blocks in chemical synthesis. One major effort involves the nickel-catalyzed net hydrolysis of traditionally inert amide C-N bonds to give carboxylic acids. Additionally, the development of synthetic routes to afford structurally complex bioactive compounds are reported. Specifically, these include the synthesis of a small library of furanoindoline compounds for structure-activity relationship studies related to the treatment of Alzheimer's disease and an alternative synthesis of the nucleobase found in the FDA-approved COVID-19 antiviral remdesivir. Finally, investigations into strained heterocyclic allenes are described. These studies have allowed for highly reactive cyclic allene intermediates to be utilized strategically in the regioselective and enantiospecific synthesis of a diverse array of densely functionalized heterocycles. Furthermore, a synthetic approach toward the synthesis of alstilobanine A is reported, where the key step hinges on a cycloaddition of an azacyclic allene intermediate. Each of the new strategies presented are expected to expand the synthetic toolbox by leveraging unique reactivity. Chapter one describes the development of a nickel-catalyzed net hydrolysis of amides. The methodology strategically employs a nickel-catalyzed esterification using 2-(trimethylsilyl)-ethanol, followed by a fluoride-mediated deprotection in a single-pot operation. The selectivity and mildness of this transformation are demonstrated through competition experiments and the net-hydrolysis of a complex valine-derived substrate. This strategy addresses a limitation in the field with regard to functional groups accessible from amides using transition metal-catalyzed C-N bond activation. Chapters two and three detail the synthesis of bioactive compounds. Chapter two specifically describes the synthesis of a small library of furanoindoline analogs for structure-activity relationship studies on the inhibition of neutral sphingomyelinase-2 and acetylcholinesterase, enzymes implicated in Alzheimer's disease. The syntheses employ a key interrupted Fischer indolization reaction where the furanoindoline product is elaborated to generate a number of analogs. Identification of the dual inhibitors represents a promising new therapeutic approach to Alzheimer's disease. Chapter three describes an alternative approach to the unnatural nucleobase fragment found in remdesivir (Veklury®), an FDA-approved antiviral for the treatment of COVID-19. The route relies on the formation of a cyanoamidine intermediate, which undergoes a Lewis acid-mediated cyclization to yield the desired nucleobase. The approach is strategically distinct from prior routes and could further enable the synthesis of remdesivir and other small-molecule therapeutics. Chapters four and five are concerned with the investigation of cyclic allene intermediates. Chapter four describes an experimental and computational study of azacyclic allenes, including the synthesis of several substituted azacyclic allene precursors, subsequent allene generation, and trapping in cycloadditions. Additionally, the computational studies performed provide insight into the underlying reasons for the observed regioselectivities and enantiospecificities. Chapter five details experimental studies of oxacyclic. Specifically, the development of a precursor to 3,4-oxacyclohexadiene and subsequent allene trapping in (4+2), (3+2), and (2+2) cycloadditions is disclosed. Additionally, the first asymmetric synthesis of a silyl triflate cyclic allene precursor was achieved, as well as enantiospecific trapping of the allene. These studies highlighted the potential for cyclic allenes to be valuable building blocks the asymmetric synthesis of heterocycles. Chapter six illustrates the development of an alternative precursor toward strained cyclic allenes and alkynes. Our studies of strained cyclic allenes revealed that, in some cases, silyl triflate precursors were inaccessible. This study shows that silyl tosylates can serve as alternative precursors to strained cyclic allenes and alkynes. Chapter seven details a strategy for the total synthesis of alstilobanine A, a monoterpene indole alkaloid. Our approach hinges on a key (4+2) Diels-Alder reaction between an acetoxy-substituted azacyclic allene intermediate and a pyrone. This cycloaddition forms two key C-C bonds and sets three of the four stereocenters found in the natural product. Current efforts to synthesize the natural product are detailed. If successful, these studies should provide efficient access to alstilobanine A and demonstrate the utility of cyclic allenes in complex molecule synthesis. Finally, chapter eight is a contribution to chemical education. The chapter outlines a new course centered around transition-metal catalysis in modern drug discovery. The course was designed to illustrate the central role of organic chemistry in driving small-molecule drug development and was taught by graduate students with mentorship from a faculty member. Additionally, experts in the fields of catalysis and drug discovery served as guest lecturers throughout the duration of the course. This chapter reflects on the experience of creating and developing the course, and aims to motivate the creation of future courses that unify fundamental concepts with applications and career outcomes.

Author : Arthur Greenberg
Publisher : John Wiley & Sons
Page : 672 pages
File Size : 23,66 MB
Release : 2002-11-11
Category : Science
ISBN : 9780471420255

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An authoritative reference to an important and ubiquitous chemical linkage The amide linkage is one of the most fundamental and widespread chemical bonds in nature, underlying the properties of a vast array of organic molecules, polymers, and materials, including peptides and proteins. Arthur Greenberg, Curt Breneman, and Joel Liebman's peerless text provides comprehensive coverage of the experimental, structural, and computational findings that shed light on the chemical and physical properties of the amide linkage, as well as its emerging applications in materials and biotechnology. Chapters in The Amide Linkage highlight how this chemical bond factors in the design of enzyme inhibitors, cyclic peptides, antibacterial agents, and emerging nanotechnology applications. This one-of-a-kind study also: * Discusses selected aspects of chemical reactions, structure, bonding, and energetics of the amide bond, including amide rotational barriers, stereochemistry, complexation, spectroscopy, and thermochemistry * Presents specific applications to supramolecular and stereospecific synthesis * Discusses key aspects of peptide and protein chemistry-such as molecular recognition, conformation, and folding-in terms of the amide linkage * Includes chapters contributed by numerous eminent chemists and biochemists Organic, medicinal, polymer, and physical chemists, as well as biochemists and materials scientists, will find The Amide Linkage to be an invaluable addition to their professional libraries.

Author : Lukas J. Gooßen
Publisher : Springer
Page : 345 pages
File Size : 13,35 MB
Release : 2012-10-30
Category : Science
ISBN : 3642342868

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Barry Trost: Transition metal catalyzed allylic alkylation.- Jeffrey W. Bode: Reinventing Amide Bond Formation.- Naoto Chatani and Mamoru Tobisu: Catalytic Transformations Involving the Cleavage of C-OMe Bonds.- Gregory L. Beutner and Scott E. Denmark: The Interplay of Invention, Observation and Discovery in the Development of Lewis Base Activation of Lewis Acids for Catalytic Enantioselective Synthesis.- David R. Stuart and Keith Fagnou: The Discovery and Development of a Palladium(II)-Catalyzed Oxidative Cross-Coupling of Two Unactivated Arenes.- Lukas Gooßen and Käthe Gooßen: Decarboxylative Cross-Coupling Reactions.- A. Stephen K. Hashmi: Gold-Catalyzed Organic Reactions.- Ben List: Developing Catalytic Asymmetric Acetalizations.- Steven M. Bischof, Brian G. Hashiguchi, Michael M. Konnick, and Roy A. Periana: The De NovoDesign of CH Bond Hydroxylation Catalysts.- Benoit Cardinal-David, Karl A. Scheidt: Carbene Catalysis: Beyond the Benzoin and Stetter Reactions.- Kenso Soai and Tsuneomi Kawasaki: Asymmetric autocatalysis of pyrimidyl alkanol.- Douglas C. Behenna and Brian M. Stoltz: Natural Products as Inspiration for Reaction Development: Catalytic Enantioselective Decarboxylative Reactions of Prochiral Enolate Equivalents. Hisashi Yamamoto: Acid Catalysis in Organic Synthesis.

Author : Milauni Mehta
Publisher :
Page : 0 pages
File Size : 30,18 MB
Release : 2023
Category :
ISBN :

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This dissertation describes the development of reaction methodologies that utilize unconventional building blocks. One major effort involves the development of a strategy to improve the practicality of the nickel-catalyzed Suzuki-Miyaura cross-coupling of amide electrophiles and a strategy for a base-mediated reduction of ketones to secondary alcohols. Furthermore, a one-pot reductive arylation of amides wherein two different nucleophiles are added to the amide carbonyl carbon is reported. This reaction, which proceeds by way of a sequential nickel-catalyzed Suzuki-Miyaura coupling and base-catalyzed reduction cascade process, directly converts amide starting materials to chiral secondary alkyl-aryl alcohol products. Finally, investigations into strained heterocyclic allenes are described. These studies detail the cyclic allene approach to the core of the manzamine alkaloid keramaphidin B, where the key step hinges on a cycloaddition of an azacyclic allene intermediate. Furthermore, the parameters controlling the regioselectivity of the Diels-Alder cycloaddition of heterocyclic allenes with a-pyrones is reported. Each of the methodologies presented is expected to expand the synthetic toolbox by leveraging unique reactivity.