Catalytic Enantioselective Allyic Amination and Etherification

本项目的重点是开发一系列实用和机械定义的与胺、氨、氨等价物、酚和脂肪醇的烯丙基胺化和醚化工艺，包括通过分子内烯丙基胺化和醚化以及分子间胺化和醚化形成氧和氮杂环的反应，然后进行合环复分解。这些反应将在一定程度上用新的含更少立体化学复杂性和更少供电子取代基的磷酰胺进行探索。为了揭示区域和对映体选择性的起源，将分离催化过程中的中间体烯丙基配合物并进行结构表征。探讨反应的机理，探讨非对映异构体烯丙基配合物的重排或亲核试剂对烯丙基中间体的攻击是否更快。该奖项来自有机和大分子化学项目，支持耶鲁大学化学系John F. Hartwig教授的研究。Hartwig教授正在研究合成含氮和氧分子的新方法。这类分子在天然产物和候选药物中无处不在，开发有效的方法来形成它们并高度控制三维结构是必不可少的。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、快速率、低催化剂负载和宽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.