Transition Metal-Catalyzed, Asymmetric Allylic Borylation and Silylation

描述（由申请人提供）：本提案旨在开发用于制备手性支链烯丙基硼酸酯和烯丙基硅烷的区域选择性和对映选择性方法。具体目标包括：1）鉴定/开发促进高度区域选择性和对映选择性烯丙基硼化和甲硅烷基化的手性过渡金属催化剂; 2）开发通过不对称烯丙基取代合成对映体富集的支化烯丙基硼酸酯的直接的、广泛适用的方法; 3）基本理解反应机理和立体化学结果，当亲核试剂不是碳，氮，和氧用于不对称烯丙基取代;和4）将该烯丙基取代方法扩展到包括用于制备对映体富集的支化烯丙基硅烷的硅亲核试剂。实现该提案的具体目标具有更广泛的相关性。从单一方法或密切相关的方法获得各种手性支化烯丙基硼酸酯和烯丙基硅烷将是有价值的，这是由于这些小分子、手性结构单元的广泛合成应用。此外，烯丙基硼化和硅烷化方法的成功发展将代表一个根本性的转变，亲核试剂通常用于不对称烯丙基取代。更好地了解机制方面可能会导致实验设计的改进，并可能提供深入了解扩大额外的手性，烯丙基取代产品的可用性。公共卫生相关性小分子手性结构单元合成方法的开发对于生物相关化合物的制备仍然具有根本重要性。近年来，获得对映体富集和/或对映体纯形式的手性候选药物分子的能力变得越来越重要。因此，获得用于合成生物活性化合物的对映体富集的手性结构单元（例如支链烯丙基硼酸酯和烯丙基硅烷）的方法已经并将继续与公共健康相关。

DESCRIPTION (provided by applicant): This proposal aims to develop regio- and enantioselective methods for the preparation of chiral, branched allylboronates and allylsilanes. Specific aims include: 1) the identification/development of chiral transition metal catalysts that promote highly regio- and enantioselective allylic borylation and silylation; 2) development of a direct, broadly applicable method for synthesis of enantioenriched, branched allyboronates by asymmetric allylic substitution; 3) fundamental understanding of reaction mechanisms and stereochemical outcomes when nucleophiles other than carbon, nitrogen, and oxygen are employed in asymmetric allylic substitutions; and 4) extension of this allylic substitution methodology to include silicon nucleophiles for the preparation of enantioenriched, branched allylsilanes. Realization of the specific aims of the proposal has the potential for much broader relevance. Access to a variety of chiral, branched allylboronates and allylsilanes from a single method or closely related methods will be of value due to the broad synthetic application of these small molecules, chiral building blocks. Furthermore, successful development of allylic borylation and silylation methods will represent a fundamental shift in terms nucleophiles commonly employed in asymmetric allylic substitutions. Greater understanding of mechanistic aspects is likely to lead to improvements in experimental design and may provide insights into expanding the availability of additional chiral, allylic substitution products. PUBLIC HEALTH RELEVANCE Development of methods for the synthesis of small molecule, chiral building blocks continues to be of fundamental importance for the preparation of biologically relevant compounds. In recent years the ability to access chiral drug candidate molecules in enantioenriched and/or enantiopure form has become increasingly important. Thus, methods to access enantioenriched chiral building blocks, such as branched allylboronates and allylsilanes, used in the synthesis of biologically active compounds has been and will continue to be relevant to public health.