Catalytic C-C Bond Forming Hydrogenations

项目概述：哈伯-博施反应就是一个例子，它支撑着一半的人类 种群，以及对映体选择性氢化，这(外消旋体的拆分)是 用来制造手性药物和农用化学成分的最重要的化学方法， 催化加氢对人类的影响比任何其他化学过程都要大。 在我们的工作之前，“C-C键形成氢化”的唯一例子是氢甲酰化， 这是目前应用最多的均相金属催化。我的实验室有 开创了一系列广泛的、新的金属催化的羰基还原偶联剂 原料亲核试剂与安全、廉价的原料还原剂(H2，2- PRH、HCO2H)和相关的氢自动转移过程(ROH=还原剂和亲电泳剂)， 将低级醇直接转化为高级醇。这些转换绕过了化学计量学 有机金属试剂及其相关的安全、选择性和废物问题 用途，为一系列经典的羰基或亚胺加成提供了一种不含副产品的替代品。在……里面 在拟议的资助期内，这一反应性模式将扩展到α-烯烃和 C-X亲核原、使用胺亲电体、形成季铵盐 立体中心和贱金属催化剂的使用。我们的最终目标是发展 将廉价的化学原料转化为价值的无害环境的方法- 添加了用于制药和农用化学品制造的积木 配料。

Project Summary: As exemplified by the Haber-Bosch reaction, which sustains half the human population, and enantioselective hydrogenation, which (beyond resolution of racemates) is the foremost chemical method used to create chiral pharmaceutical and agrochemical ingredients, catalytic hydrogenation has had a greater impact on humanity than any other chemical process. Prior to our work, the sole example of a “C-C bond forming hydrogenation” was hydroformylation, which is now the largest application of homogenous metal catalysis. My laboratory has pioneered a broad, new family of metal-catalyzed carbonyl reductive couplings that exploit feedstock pronucleophiles in combination with safe, inexpensive feedstock reductants (H2, 2- PrOH, HCO2H), and related H2-autotransfer processes (ROH = reductant & proelectrophile) that directly convert lower alcohols to higher alcohols. These transformations bypass stoichiometric organometallic reagents and the issues of safety, selectivity, and waste associated with their use, offering a byproduct-free alternative to a range of classical carbonyl or imine additions. In the proposed funding period, this reactivity pattern will be extended to couplings of α-olefins and C-X pronucleophiles, the use of amine proelectrophiles, the formation of quaternary stereocenters and use of base metal catalysts. Our ultimate objective is to develop environmentally benign methods for the conversion of inexpensive chemical feedstocks to value- added building blocks for use in the manufacture of pharmaceutical and agrochemical ingredients.