Developing an Understanding of Asymmetric Induction

描述(由申请人提供)：这项提案的广泛、长期目标是开发新的合成方法，使其能够制备有机和药物化学的重要中间体。我们的方法首次使从芳基溴化物中大规模合成对映体富集二芳基甲醇成为可能。该方法将应用于合成具有重要药效团的富含对映体的杂环化合物，如呋喃和吡啶。我们还开发了几条合成吡喃酮、呋喃糖醛、呋喃和吡咯的新路线。使用我们的方法可以制备具有高对映体选择性的医药上重要的杂环化合物。我们以一种用途广泛的1-烯基-1，1-双金属中间体为原料，一锅法合成了α-羟基酮、烯丙醇和取代环丙烷。这些方法将在复杂分子合成中发挥重要作用。这项建议的具体目标是：1.开发将芳基、乙烯基和烷基溴化物直接转化为对映体浓缩醇的方法。二、杂环合成新方法介绍。用于合成复杂分子的1-烯基-1，1-双金属试剂的开发。该项目介绍了合成重要的手性构建块的新方法，这些构建块不易获得，但在与健康相关的应用中有实用价值，特别是在合成对映体富集型药物方面。

DESCRIPTION (provided by applicant): The broad, long-term objectives of this proposal are to develop new synthetic methods that enable the preparation of important intermediates for organic and medicinal chemistry. Our methods make possible, for the first time, the large-scale synthesis of enantioenriched diarylmethanols from aryl bromides. This method will be applied to the synthesis of enantiomerically enriched heterocycles bearing important pharmacophores, such as furans and pyridines. We have also developed several new routes to pyranones, furanosidic aldehydes, furans, and pyrroles. These medicinally important heterocycles can be prepared with high enantioselectivities using our methods. We have developed one-pot synthesis of a-hydroxy ketones, allylic alcohols, and substituted cyclopropanes from a versatile 1-alkenyl-1,1-bimetallic intermediate. These methods will be useful in complex molecule synthesis. The Specific Aims of this proposal are: I. Development of Direct Methods for Conversion of Aryl, Vinyl, and Alkyl Bromides to Enantioenriched Alcohols. II. Introduction of New Methods For Heterocycle Syntheses. III: Development of 1-Alkenyl-1,1-Bimetallic Reagents for Complex Molecule Synthesis. This project presents new methods to synthesize important chiral building blocks that were not easily accessible, but find utility in health-related applications, particularly in the synthesis of enantioenriched pharmaceutical agents.