Stereoconvergent Nickel-Catalyzed Arylation of Benzylic Electrophiles

描述(由申请人提供)：本提案概述了一项研究计划，该计划旨在开发一种新的碳-碳键形成方法，用于通过立体聚合镍催化的苯基亲电试剂的芳基化反应来合成手性二芳基烷。手性二芳基烷是一类重要的有机结构，常见于商业化的单对映体药物中，包括舍曲林(ZoloftTM)、托特罗定(Detro TM)和许多抗组胺药物。现有的制备单一对映体二芳基烷的方法依赖于晚期拆分，在此过程中丢弃了一半的材料。我们计划将从化学计量体系模型研究中获得的机理洞察力应用于开发一种催化的苄基芳基化反应，该反应能够将外消旋的苯基亲电物质转化为对映体富含1，1-二芳基的烷烃。在此过程中，我们将推进相对较新的镍催化的C-C成键化学，该化学已经开始证明其在合成有机化学领域的价值，用于合成具有生物活性的天然产物和与药物相关的核心结构。

DESCRIPTION (provided by applicant): This proposal outlines a research program designed to develop new carbon-carbon bond-forming methodology for the synthesis of chiral diarylalkanes by stereoconvergent nickel- catalyzed arylation of benzylic electrophiles. Chiral diarylalkanes are an important class of organic structures commonly found in commercialized single-enantiomer pharmaceuticals including sertraline (ZoloftTM), tolterodine (DetrolTM), and many antihistamines. Existing methods for the preparation of single-enantiomer diarylalkanes rely on late-state resolution, discarding half of the material in the process. We plan to apply mechanistic insight gained from model studies on a stoichiometric system to the development of a catalytic, benzylic arylation reaction capable of converting racemic benzylic electrophiles to enantioenriched 1,1-diarylalkanes. In doing so, we will be advancing relatively new nickel-catalyzed C-C bond-forming chemistry which has already begun to prove its value to the field of synthetic organic chemistry for the synthesis of bio-active natural products and pharmaceutically-relevant core structures.