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，用于通过立体结合的镍催化苯甲酸电泳芳基化的镍催化芳基化，以合成手性日记藻。手性日粮是一类重要的有机结构，在包括舍曲林（ZoloftTM），Tolterodine（detroltm）和许多抗组胺药在内的商业化单对异构体药物中常见的有机结构。现有制备单一植物的方法依赖于晚期分辨率，在此过程中丢弃了一半的材料。我们计划应用从化学计量系统的模型研究获得的机械洞察力，以开发能够转化外星苯并苯基电力的催化，苯并芳基化反应，从而将外星苯二的电力转换为映射的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的C-C键形成化学，该化学已经开始证明其对合成生物活性天然产物的合成有机化学领域的价值，并证明了它的生物活性天然产物和与药物相关的核心结构。