Enantioselective Catalytic Chlorosilane Reactions

由刘易斯碱催化剂和氯硅烷产生的高价硅络合物 是非常活泼的中间体，并且仍然是 发展有机合成中的新化学方法学。独特的反应性 氯硅烷的特性、无毒性和易得性， 一系列化学方法和过程。该提案旨在创新能力， 氯硅烷在刘易斯碱催化条件下提供碳亲核试剂 通过综合实验和计算研究，并将其应用于 与容易获得的非活化的酮和酮亚胺的新的缩合反应。 这些具有挑战性的转化将通过以下方式呈现对映选择性： 开发概念上新型的手性刘易斯碱催化剂。的效用 所得到的方法将通过药物的不对称合成来证明。 和生物相关分子。研究计划的目标包括推进 氯代硅烷的刘易斯碱催化及其新反应 开发，将提供快速，有效地获得新的手性结构单元 带有氧和氮取代的四元立构中心。我们将专注于 可以提供手性合成中间体的转化， 用目前可用的方法无法获得或很难获得。结果 有望改变氯硅烷用于不对称合成的方式。

Hypervalent silicon complexes generated from Lewis base catalysts and chlorosilanes are very reactive intermediates and continue to be an important source for the development of new chemical methodologies in organic synthesis. The unique reactivity profiles, non-toxicity and ready availability of chlorosilanes have yielded an impressive array of chemical methods and processes. This proposal seeks to innovate the ability of chlorosilanes to deliver carbon nucleophiles under Lewis base catalysis conditions through integrated experimental and computational investigations, and to apply it to novel condensation reactions with readily available non-activated ketones and ketimines. These challenging transformations will be rendered enantioselective through the development of conceptually new classes of chiral Lewis base catalysts. The utility of the resulting methods will be demonstrated by the asymmetric synthesis of pharmaceuticals and biologically relevant molecules. Goals of the research program include advancing Lewis base catalysis of chlorosilanes at the fundamental level, and new reaction development that will provide rapid, efficient access to novel chiral building blocks bearing the oxygen- and nitrogen-substituted quaternary stereocenters. We will focus on the transformations that can provide chiral synthetic intermediates that are either inaccessible or very difficult to obtain with currently available methods. The results are expected to transform the way chlorosilanes are utilized in asymmetric synthesis.