Convergent Synthesis via Asymmetric Catalysis

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DESCRIPTION (provided by applicant): The focus of this project is the development and application of nickel-catalyzed carbon-carbon bond-forming reactions for the synthesis of medicinally important organic molecules. Methods that we have developed will be utilized in the synthesis of several amphidinolide natural products, sieboldine A, and dioxepandehydrothyrsiferol. None of these has previously been prepared by total synthesis. Two new classes of nickel-catalyzed reactions will be developed. Both involve the coupling of unactivated alpha olefins, which are prepared in metric ton amounts annually. One new class of coupling reaction under development involves electrophiles with cumulated double bonds such as carbon dioxide, ketenes, and carbodiimides. Each of these unites readily available starting materials to make synthetically valuable compounds, acrylic acids, enones, and amidines, respectively. The reactions in the other class all involve conjugate addition reactions, with the advance in this case being that the alpha olefin, an alkene without any obvious activating group, functions as the nucleophile. The focus of this project is the development and application of nickel-catalyzed carbon- carbon bond-forming reactions for the synthesis of medicinally important organic molecules, including amphidinolides, sieboldine A, and dioxepandehydrothyrsiferol. In another part of this project, two new classes of nickel-catalyzed reactions will be developed, and each of these unites readily available starting materials to make synthetically valuable compounds.