Department of Chemistry, Lancaster University, Lancaster LA1 4YB, U.K.
J Org Chem. 2022 Aug 5;87(15):10256-10276. doi: 10.1021/acs.joc.2c01240. Epub 2022 Jul 8.
As saturated heterocyclic building blocks become increasingly popular in medicinal chemistry and drug discovery programs, expansion of the synthetic toolkit to novel stereofunctionalized heterocycles is a priority. Herein, we report the development of a palladium-catalyzed decarboxylative asymmetric allylic alkylation reaction to access a broad range of enantioenriched α-difunctionalized 5- and 6-membered sulfones from easily accessible racemic starting materials. The allylic alkylation step was found to occur with high levels of enantioselectivity as a result of a palladium-mediated dynamic kinetic resolution of / enolate intermediates. This methodology paves the way to hitherto unexplored stereodefined cyclic sulfones for medicinal chemistry applications.
随着饱和杂环砌块在药物化学和新药研发项目中变得越来越受欢迎，将合成工具包扩展到新型立体官能化杂环是当务之急。在此，我们报告了钯催化的脱羧不对称烯丙基烷基化反应的发展，该反应可从易得的外消旋起始原料中获得广泛的对映体富集的α-二官能化 5-和 6-元砜。烯丙基烷基化步骤发生了高对映选择性，这是由于钯介导的 / 烯醇化物中间体的动态动力学拆分。该方法为药物化学应用开辟了 hitherto 尚未探索的具有立体定义的环状砜。
