Stereoconvergent Nickel-Catalyzed Arylation of Benzylic Electrophiles

苯甲基亲电子试剂的立体会聚镍催化芳基化

• 批准号: 8455650
• 负责人: Nathan David Schley
• 金额: $ 4.71万
• 依托单位: CALIFORNIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-02-01 至 2016-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8455650
• 关键词: Antihistamines; Biological; Biological Factors; Biological Models; Carbon; Carbonates; Catalysis; Chemistry; Complex; Coupling; Development; Electron Transport; Electrons; Human body; Image; Investigation; Kinetics; Left; Ligands; Methodology; Methods; Nickel; Organic Chemistry; Oxygen; Pharmaceutical Preparations; Pharmacologic Substance; Preparation; Process; Property; Reaction; Reagent; Research; Resolution; Sertraline; Structure; Study models; System; Tolterodine; United States Food and Drug Administration; aryl halide; catalyst; cost; design; enantiomer; improved; insight; programs; public health relevance

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.

描述（由申请人提供）：该提案概述了一项研究计划，旨在开发新的碳-碳键形成方法，用于通过苄基亲电试剂的立体会聚镍催化芳基化合成手性二芳基烷烃。手性二芳基烷烃是一类重要的有机结构，通常存在于商业化的单一对映体药物中，包括舍曲林（ZoloftTM）、托特罗定（DetrolTM）和许多抗组胺药。制备单一对映体二芳基烷烃的现有方法依赖于后期拆分，在该过程中丢弃一半的材料。我们计划将从化学计量体系的模型研究中获得的机理见解应用于催化，苄基芳基化反应的发展，该反应能够将外消旋苄基亲电试剂转化为对映体富集的1，1-二芳基烷烃。在此过程中，我们将推进相对较新的镍催化C-C键形成化学，该化学已经开始证明其在合成有机化学领域的价值，用于合成生物活性天然产物和药物相关核心结构。