New Domino Reactions For Enantioselective Synthesis

用于对映选择性合成的新多米诺反应

• 批准号: 7235852
• 负责人: Jeffrey S Johnson
• 金额: $ 3.97万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7235852
• 关键词: carbanion; catalyst; chemical addition; chemical bond; chemical reaction; chemical substitution; chemical synthesis; metal complex; method development; molecular rearrangement; silicon compounds; stereoisomer

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.

描述（由申请人提供）：具有有趣的生物特性的化合物的有效实验室制备是生物医学进步的必要组成部分。该提案的总体目标是实质性地增加可用于合成复杂有机分子的工具。具体研究将集中于基于酰基硅烷重排的新型催化多米诺骨牌反应的开发。酰基硅烷的亲核加成通常会引发硅的碳氧重排，并在异常温和的条件下产生以碳为中心的阴离子。这种简单的重排将作为各种对映选择性键结构的基础，这些结构的不同之处在于用于捕获原位生成的碳负离子的亲电子试剂（醛、亚胺、硝酮、环氧化物、卤代烷）的特性。从单一的常见中间体，可以合成多种结构多样的手性构件。在许多情况下，预计多米诺骨牌反应最终​​将再生亲核物质，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，并且为所提议的反应开发新催化剂是该研究计划的重要组成部分。快速获得非蛋白氨基酸、聚乙酸酯结构单元和各种其他有用的手性合成子是这项拟议研究的预期成果。