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

催化剂控制的脱氢 Si-O 偶联对简单醇进行对映选择性硅烷化

• 批准号: 388204995
• 负责人: Professor Dr. Martin Oestreich
• 金额: --
• 依托单位: Institut für Chemie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2017
• 资助国家: 德国
• 起止时间: 2016-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/388204995?language=en
• 关键词: Enantioselective; Silylation; Simple; Alcohols; Catalyst

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.

在过去的十年中，通过硅烷化的醇的非酶动力学拆分（KR）迅速确立了自己作为常见酰化的替代方案。亚化学计量量的手性咪唑型碱与氯硅烷一起使KR和相关的广泛的1，2-和1，3-二醇基序的去对称化。尝试拆分一元醇，即，简单的仲醇或甚至叔醇，迄今为止只取得了有限的成功。该领域最近通过鉴定手性布朗斯台德酸作为催化剂而进一步发展，其中之一首次允许使用六甲基二硅氮烷作为甲硅烷基化试剂对未官能化的醇进行KR。我们的立体选择性醇硅烷化的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。我们几年前开发了试剂和催化剂控制的KRs，但高选择性因子仅用供体官能化的并且因此偏置的醇实现。经过大量的实验，我们发现了一个强大的催化剂/氢硅烷组合，介导简单的醇和市售氢硅烷之间的缩合偶联，具有高效率。该项目旨在将这种新方法建立在良好的基础上，包括广泛的底物范围和扩展到去对称化反应。