Enantioselective Silylation of Simple Alcohols by Catalyst-Controlled Dehydrogenative Si-O Coupling

在过去的十年里，通过硅基化的醇的非酶动力学分解（KR）迅速确立了自己作为一种替代常见的酰化。亚化学计量量的手性咪唑型碱基与氯硅烷一起使KR和相关的1,2-和1,3-二醇基序的脱对称成为可能。迄今为止，试图解决单醇，即简单的仲醇甚至叔醇，只取得了有限的成功。最近，手性Brønsted酸作为催化剂的鉴定进一步推进了这一领域的发展，其中一种催化剂首次允许以六甲基二矽氮烷作为硅基化试剂的非官能化醇的KR。我们的立体选择性醇硅基化方法是基于过渡金属催化的醇和氢硅烷的硅氧偶联，释放二氢作为唯一的废物。试剂控制和催化剂控制的KRs在几年前就被我们开发出来了，但高选择性因子只在供体功能化和偏倚醇上实现。经过大量的实验，我们发现了一种强大的催化剂/氢硅烷组合，它可以高效地介导简单醇和市售氢硅烷之间的脱氢偶联。该项目的目的是使这种新方法有一个良好的基础，包括广泛的底物范围和扩展到不对称反应。

Non-enzymatic kinetic resolution (KR) of alcohols through silylation rapidly established itself as an alternative to the common acylation in the last ten years. Substoichiometric amounts of chiral imidazole-type bases together with chlorosilanes enabled the KR and the related desymmetrization of a broad range of 1,2- and 1,3-diol motifs. Attempts to resolve monools, i.e., simple secondary or even tertiary alcohols, have only been met with limited success so far. The field was recently further advanced by the identification of chiral Brønsted acids as catalysts, and one of them, for the first time, allowed for the KR of unfunctionalized alcohols using hexamethyldisilazane as silylation reagent. Our approach to stereoselective alcohol silylation is based on transition-metal-catalyzed silicon-oxygen coupling of alcohols and hydrosilanes, liberating dihydrogen as the sole waste. Both reagent- and catalyst-controlled KRs were developed by us a few years ago but high selectivity factors were only achieved with donor-functionalized and as such biased alcohols. After considerable experimentation, we found a powerful catalyst/hydrosilane combination that mediates the dehydrogenative coupling between simple alcohol and commercially available hydrosilanes with high efficiency. The project aims at putting this new method on a sound basis, including broad substrate scope and extension to desymmetrization reactions.