Catalytic Enantioselective Allyic Amination and Etherification

该项目的重点是开发一系列实用的和机械定义的烯丙基胺化和醚化工艺与胺，氨，氨等价物，酚和脂肪醇，包括反应，形成氧和氮杂环通过分子内烯丙基胺化和醚化和分子间胺化和醚化，然后闭环复分解。这些反应将被探索，部分，与新的亚磷酰胺含有较少的立体化学复杂性和较少的供电子取代基。为了揭示区域和对映体选择性的起源，烯丙基络合物，在催化过程中的中间体将被分离和结构表征。反应的机理将被探索，探索非对映体烯丙基络合物的重排或亲核试剂对烯丙基中间体的攻击是否更快。耶鲁大学化学系的哈特维希说。哈特维希教授正在研究合成含氮和氧分子的新方法。这些分子在天然产物和药物候选物中普遍存在，并且开发具有高度控制三维结构的有效方法来形成它们是必不可少的。通过对形成这些分子的反应进行基本的分子水平的理解，Hartig教授的研究有望在设计具有高选择性，快速，低催化剂负载和广泛范围的新型有效催化剂方面取得重要进展。

This project is focused on the development of a series of practical and mechanistically defined allylic amination and etherification processes with amines, ammonia, ammonia equivalents, phenols and aliphatic alcohols, including reactions to form oxygen and nitrogen heterocycles by intramolecular allylic amination and etherification and intermolecular amination and etherification followed by ring-closing metathesis. These reactions will be explored, in part, with new phosphoramidites containing less stereochemical complexity and fewer electron-donating substituents. To uncover the origin of regio- and enantioselectivity, allyl complexes that are intermediates in the catalytic process will be isolated and structurally characterized. The mechanism of the reactions will be probed, exploring whether rearrangements of diastereomeric allyl complexes or attack of nucleophiles on the allyl intermediates is faster.This award from the Organic and Macromolecular Chemistry Program supports the research of Professor John F. Hartwig, of the Department of Chemistry at Yale University. Professor Hartwig is developing new methods for the synthesis of molecules containing nitrogen and oxygen. Such molecules are ubiquitous in natural products and in pharmaceutical candidates, and the development of effective methods for their formation with high control of three-dimensional structure is essential. By pursuing a fundamental, molecular-level understanding of the reactions forming such molecules, Professor Hartig's research is expected to lead to important advances in the design of new and effective catalysts with high selectivity, fast rates, low catalyst loadings, and broad scope.