Pfizer Global Research and Development, Groton Laboratories, Eastern Point Road, Groton, Connecticut 06340, USA.
J Org Chem. 2012 Mar 16;77(6):2999-3004. doi: 10.1021/jo3001063. Epub 2012 Feb 29.
2,2,2-Trichloromethylcarbinols are 1 are valuable synthetic intermediates with a multitude of uses. A scalable procedure for the synthesis of TMS-protected-2,2,2-trichloromethylcarbinols and 2,2,2-trichloromethylcarbinols 1 was developed that employs the in situ generation and reaction of trimethyl(trichloromethyl)silane (CCl(3)-TMS). The procedure avoids the exposure of the carbonyl compounds to the strongly basic conditions typically used for this transformation and also avoids isolation of the difficult-to-handle CCl(3)-TMS. This procedure was applied to diastereoselective trichloromethyl additions to 2-substituted 4-piperidinones and to reactions with a variety of structurally diverse aldehydes and ketones.
2,2,2-三氯甲基甲醇 1 是一种具有多种用途的有价值的合成中间体。本研究开发了一种可规模化的 TMS-保护-2,2,2-三氯甲基甲醇和 2,2,2-三氯甲基甲醇 1 的合成方法，该方法采用三甲基（三氯甲基）硅烷（CCl(3)-TMS）的原位生成和反应。该方法避免了羰基化合物暴露于通常用于该转化的强碱性条件下，也避免了难以处理的 CCl(3)-TMS 的分离。该方法应用于 2-取代的 4-哌啶酮的立体选择性三氯甲基加成反应，以及与各种结构多样的醛和酮的反应。
