New Domino Reactions For Enantioselective Synthesis

描述(由申请人提供)：高效的实验室制备具有有趣的生物学特性的化合物是生物医学进步中的一个必要组成部分。这项提议的广泛目标是实质性地增加可用于合成复杂有机分子的工具。具体的研究将集中在开发基于涉及酰基硅烷重排的新的催化多米诺反应。在异常温和的条件下，酰基硅烷的亲核加成通常会引发硅的碳氧重排和碳中心阴离子的生成。这种简单的重排将作为各种对映选择性键结构的基础，这些结构在捕获原位生成的碳负离子所用的亲电体(醛、亚胺、硝酮、环氧化物、卤代烷)的同一性上有所不同。从单一的普通中间体出发，可以合成多种结构不同的手性构筑块。在许多情况下，预计多米诺骨牌反应最终将再生亲核物种，从而允许开发新的催化反应。在亲核试剂是手性的情况下，不对称变体将是可能的，为拟议的反应开发新的催化剂是这一研究计划的重要组成部分。快速获得非蛋白来源的氨基酸、聚醋酸酯构建块和各种其他有用的手性合成子是这项拟议研究的预期结果。

DESCRIPTION (provided by applicant): 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.