EaStChem, School of Chemistry, University of St Andrews, North Haugh, St Andrews, Fife, KY16 9ST, UK.
Angew Chem Int Ed Engl. 2020 Sep 14;59(38):16572-16578. doi: 10.1002/anie.202004354. Epub 2020 Jul 16.
A highly enantioselective isothiourea-catalyzed acylative kinetic resolution (KR) of acyclic tertiary alcohols has been developed. Selectivity factors of up to 200 were achieved for the KR of tertiary alcohols bearing an adjacent ester substituent, with both reaction conversion and enantioselectivity found to be sensitive to the steric and electronic environment at the stereogenic tertiary carbinol centre. For more sterically congested alcohols, the use of a recently-developed isoselenourea catalyst was optimal, with equivalent enantioselectivity but higher conversion achieved in comparison to the isothiourea HyperBTM. Diastereomeric acylation transition state models are proposed to rationalize the origins of enantiodiscrimination in this process. This KR procedure was also translated to a continuous-flow process using a polymer-supported variant of the catalyst.
已开发出一种对非环叔醇进行高对映选择性异硫脲催化酰基动力学拆分 (KR) 的方法。带有相邻酯取代基的叔醇的 KR 可达到高达 200 的选择性因子，反应转化率和对映选择性都发现对立体中心的立体叔醇碳原子的空间和电子环境敏感。对于更具空间位阻的醇，最近开发的异硒脲催化剂的使用是最佳的，与 HyperBTM 异硫脲相比，实现了等效的对映选择性，但转化率更高。提出了非对映选择性酰化过渡态模型，以合理说明该过程中对映体选择性的起源。该 KR 程序也使用催化剂的聚合物负载变体转化为连续流过程。
