中国科学院上海有机化学研究所施世良团队报道了酮的动态动力学不对称芳基化和烯基化。相关研究成果发表在2023年2月17日出版的《科学》。

尽管富含对映体的醇在药物化学、全合成和材料科学中具有重要意义，但高效和选择性地构建具有两个相邻立体中心的富含对映物的叔醇仍然是一个重大挑战。

研究人员报道了一种通过对映异构、镍催化的有机硼酸酯与外消旋、非活化酮的加成来制备它们的平台。通过芳基和烯基亲核试剂的动态动力学不对称加成，在一个步骤中制备了几类重要的α，β-手性叔醇，具有高水平的非对映选择性和对映选择性。应用这一方案来修饰几种专业药物，并快速合成生物相关分子。研究人员预计这种镍催化的无碱酮外消旋化工艺将是开发动态动力学过程的一种广泛适用的策略。

附：英文原文

Title: Dynamic kinetic asymmetric arylation and alkenylation of ketones

Author: Lin-Xin Ruan, Bo Sun, Jia-Ming Liu, Shi-Liang Shi

Issue&Volume: 2023-02-17

Abstract: Despite the importance of enantioenriched alcohols in medicinal chemistry, total synthesis, and materials science, the efficient and selective construction of enantioenriched tertiary alcohols bearing two contiguous stereocenters has remained a substantial challenge. We report a platform for their preparation through the enantioconvergent, nickel-catalyzed addition of organoboronates to racemic, nonactivated ketones. We prepared several important classes of α,β-chiral tertiary alcohols in a single step with high levels of diastereo- and enantioselectivity through a dynamic kinetic asymmetric addition of aryl and alkenyl nucleophiles. We applied this protocol to modify several profen drugs and to rapidly synthesize biologically relevant molecules. We expect this nickel-catalyzed, base-free ketone racemization process to be a widely applicable strategy for the development of dynamic kinetic processes.

DOI: ade0760

Source: https://www.science.org/doi/10.1126/science.ade0760