Progress Towards The Total Synthesis Of Citrinadin A

Author : Jacob Edward Dander
Publisher :
ISBN 13 :
Total Pages : 419 pages
Book Rating : 4.:/5 (116 download)

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Download or read book Nickel-Catalyzed Amide Carbon-Nitrogen Bond Activation Methodologies and Progress Toward the Total Synthesis of Dodecahedrane written by Jacob Edward Dander and published by . This book was released on 2020 with total page 419 pages. Available in PDF, EPUB and Kindle. Book excerpt: This dissertation describes efforts in the field of nickel-catalyzed amide C-N bond activations and studies toward the total synthesis of dodecahedrane. Although amide C-N bonds are generally considered inert, recent progress in the activation of these bonds has allowed for their use as synthetic building blocks. Herein, several nickel-catalyzed transformations of amides and strategies to improve the practicality of these reactions are outlined. Each of these studies highlights the utility of nickel catalysis and amides in the context of organic synthesis. Furthermore, a synthetic strategy for and experimental progress toward the synthesis of dodecahedrane are reported. The realization of this total synthesis is expected to push our understanding of molecular reactivity and represent a milestone in the field of total synthesis. Chapters one, two, and three describe the development of transformations and experimental techniques that improve the scope and practicality of nickel-catalyzed activations of aryl amide C-N bonds. More specifically, chapter one describes a nickel-catalyzed alkylation of amides to access aryl-alkyl ketone products. This catalytic methodology represents a mild approach to synthesizing these products that is complementary to the Weinreb ketone synthesis. Chapter two details a strategy for the benchtop delivery of Ni(cod)2. The air- and moisture-sensitivity of this important nickel precatalyst limits its general utility. By utilizing paraffin-Ni(cod)2 capsules, a variety of nickel-catalyzed transformations, including aryl amide cross-couplings, can be performed outside of a glovebox. Chapter three outlines efforts to deploy paraffin-Ni(cod)2 capsules in an undergraduate organic chemistry laboratory. Through the use of these reagents in an esterification of an aryl amide, students gain meaningful insights into frontiers in cross-coupling research, nickel catalysis, and the use of amides in synthetic organic chemistry. Chapters four and five are concerned with the development of nickel-catalyzed transformations of aliphatic amides. Chapter four specifically details efforts to develop a nickel-catalyzed transamidation of aliphatic secondary amides. Through the use of a two-step activation-cross-coupling approach, we have achieved a mild and general solution to this long-standing problem in organic chemistry. Chapter five describes a method for performing arylations of aliphatic amides on the benchtop. By employing paraffin-Ni(cod)2/Benz-ICy[TM]HCl capsules, Suzuki-Miyaura cross-couplings of aliphatic amides to generate aryl-alkyl ketones can be achieved without the need for glovebox manipulations. Both of these studies expand the field of nickel-catalyzed amide C-N bond activations and promote amides as useful synthetic building blocks. Chapter six illustrates a chemoenzymatic approach to enantioselective transformations of amides. The development of a one-pot Suzuki-Miyaura cross-coupling and ketoreductase-mediated reduction allows for rapid, selective access to enantioenriched alcohol products from amides. This methodology represents the first enantioselective transformation of amides that relies on amide C-N bond activation and is expected to guide the development of other asymmetric transformations of amides. Finally, chapter seven details a strategy for the total synthesis of the complex hydrocarbon dodecahedrane. Our proposed symmetry-based approach to this fascinating icosahedral molecule relies on an ambitious [2+2+2+2+2] cyclization to assemble five key C-C bonds in a single synthetic operation. Current efforts to synthesize the necessary substrate for the [2+2+2+2+2] cyclization are detailed. If successful, these studies should provide efficient access to dodecahedrane and are expected to lead to insights into new modes of reactivity.