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.

在过去十年中，通过硅烷化对醇进行非酶动力学拆分 (KR) 迅速成为普通酰化的替代方案。亚化学计量的手性咪唑型碱基与氯硅烷一起实现了 KR 以及各种 1,2- 和 1,3- 二醇基序的相关去对称化。迄今为止，解析一元醇（即简单的仲醇甚至叔醇）的尝试仅取得了有限的成功。最近，通过鉴定手性布朗斯台德酸作为催化剂，该领域得到进一步发展，其中一种首次允许使用六甲基二硅氮烷作为甲硅烷基化试剂对非官能化醇进行 KR。我们的立体选择性醇硅烷化方法基于过渡金属催化的醇和氢硅烷的硅氧偶联，释放出氢气作为唯一的废物。我们几年前开发了试剂控制和催化剂控制的 KR，但只有通过供体官能化和偏向醇才能实现高选择性因子。经过大量实验，我们发现了一种强大的催化剂/氢硅烷组合，可以高效地介导简单醇和市售氢硅烷之间的脱氢偶联。该项目旨在为这种新方法奠定良好的基础，包括广泛的底物范围和扩展到去对称反应。