Department of Chemistry, Yale University, P.O. Box 208107, New Haven, Connecticut 06520-8107, United States.
J Org Chem. 2022 Aug 5;87(15):10250-10255. doi: 10.1021/acs.joc.2c01231. Epub 2022 Jul 13.
Noncanonical amino acids (NCAAs) are imperative to many facets of chemistry and biology. Herein, we report a method for the reductive hydrodifluoroalkylation of olefins that utilizes triethylamine base as the terminal reductant. The alkene acceptors include a range of electronically diverse alkenes, chief among them, dehydroalanine in variously protected forms, which provides access to synthetically relevant NCAA scaffolds under mild and general reaction conditions. We have demonstrated that a chiral auxiliary may be incorporated to provide diastereocontrol for pro-stereogenic substrates. Mechanistically motivated experiments provide some insight into the reaction mechanism, which supports a terminal step involving proton transfer for electron-poor olefins, while H atom transfer assisted by a thiol cocatalyst may complete the catalytic cycle for electron-rich olefins. The protocol is found to be compatible with additions to complex molecules, including the natural product thiostrepton.
非天然氨基酸（NCAA）在化学和生物学的许多方面都至关重要。在此，我们报告了一种利用三乙胺作为末端还原剂还原氢二氟烷基化烯烃的方法。烯烃受体包括一系列电子不同的烯烃，其中主要包括各种保护形式的脱氢丙氨酸，该方法在温和且通用的反应条件下为合成相关 NCAA 支架提供了途径。我们已经证明，可以引入手性助剂来为立体中心底物提供非对映体控制。受反应机制启发的实验提供了一些关于反应机制的见解，该机制支持涉及缺电子烯烃的末端质子转移步骤，而含硫辅催化剂辅助的氢原子转移则可能完成富电子烯烃的催化循环。该方案被发现与复杂分子的加成兼容，包括天然产物硫链丝菌素。
