Catalytic C-C Bond Forming Hydrogenations

项目摘要：以维持一半人类生命的哈伯-博世反应为例 人口，和对映选择性氢化，这（超出了外消旋体的分辨率）是 用于生产手性药物和农用化学品成分的最重要的化学方法， 催化氢化对人类的影响比任何其他化学过程都大。 在我们的工作之前，“C-C键形成氢化”的唯一例子是氢化， 这是目前均相金属催化的最大应用。我的实验室 开创了一个广泛的，新的家庭金属催化羰基还原偶联，利用 原料亲核试剂与安全、廉价的原料还原剂（H2，2- PrOH，HCO 2 H）和相关的H2-自动转移过程（ROH =还原剂和亲电试剂）， 将低级醇直接转化为高级醇。这些转换绕过化学计量 有机金属试剂和与其相关的安全性，选择性和废物问题 使用，提供了一个无副产物的替代一系列经典的羰基或亚胺加成。在 在拟议的资助期内，这种反应模式将扩展到α-烯烃的偶联， C-X亲核试剂，利用胺亲电试剂，形成季铵型 立构中心和使用贱金属催化剂。我们的最终目标是发展 将廉价的化学原料转化为价值的环境友好方法- 用于制造药物和农用化学品的添加的结构单元 成分.

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.