Transition Metal-Catalyzed, Asymmetric Allylic Borylation and Silylation

描述（由申请人提供）：本提案旨在开发区域和对映选择性方法，用于制备手性，支化的烯丙基硼酸盐和烯丙基硅烷。具体目标包括：1)鉴定/开发手性过渡金属催化剂，促进高区域和对映选择性的烯丙基硼化和硅化；2)通过不对称烯丙基取代合成对映体富集的支链烯丙基硼酸酯的直接、广泛适用的方法；3)对非对称烯丙基取代中除碳、氮和氧以外的亲核试剂的反应机理和立体化学结果的基本理解；4)扩展这种烯丙基取代方法，包括硅亲核试剂，用于制备对映体富集的支化烯丙基硅烷。实现该建议的具体目标可能具有更广泛的相关性。由于这些小分子，手性构建块的广泛合成应用，从单一方法或密切相关的方法获得各种手性，支化烯丙基硼酸盐和烯丙基硅烷将具有价值。此外，烯丙基硼化和硅基化方法的成功发展将代表不对称烯丙基取代中常用的亲核试剂的根本转变。对机理方面的更深入了解可能会导致实验设计的改进，并可能为扩大其他手性，烯丙基替代产品的可用性提供见解。开发小分子手性构建块的合成方法对于制备与生物相关的化合物仍然具有根本性的重要性。近年来，以对映体富集和/或对映体纯形式获得手性候选药物分子的能力变得越来越重要。因此，获取用于合成生物活性化合物的富集对映体的手性构件（如支化烯丙基硼酸盐和烯丙基硅烷）的方法已经并将继续与公共卫生相关。

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.