The efficient laboratory preparation of compounds exhibiting interesting biological properties is a necessary component in biomedical advances. The broad objective of this proposal is to substantively add to the tools available for the synthesis of complex organic molecules. Specific research will focus on the development of new catalytic domino reactions based on rearrangements involving acylsilanes. Nucleophilic additions to acylsilanes often trigger carbon-to-oxygen rearrangement of silicon and generation of carbon-centered anions under exceptionally mild conditions. This facile rearrangement will serve as the basis for a variety of enantioselective bond constructions that differ in the identity of the electrophile (aldehyde, imine, nitrone, epoxide, alkyl halide) employed to trap the in situ-generated carbanion. From a single common intermediate, the synthesis of a broad range of structurally diverse chiral building blocks should be achieved. In many cases, it is anticipated that the domino reaction will ultimately regenerate the nucleophilic species, allowing for the development of new catalytic reactions. In the cases where the nucleophile is chiral, asymmetric variants will be possible and the development of new catalysts for the proposed reactions is an important component of this research plan. Rapid access to nonproteinogenic amino acids, polyacetate building blocks, and a variety of other useful chiral synthons is an expected outgrowth of this proposed research.
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