中国科学院上海有机化学研究所储玲玲团队报道了，镍催化氢原子和基团转移选择性加氢官能化烯基氟化物的反应进展和机理研究。相关研究成果发表在2024年4月15日出版的《美国化学会杂志》。

由于氟原子的独特作用，高效构建高价值烷基氟化物在现代药物开发中引起了极大的兴趣。然而，从简单的起始材料高效组装高度功能化的，手性C（sp³）-F支架的对映选择性催化策略尚未得到充分利用。

该文中，研究人员展示了一种镍催化的自由基转移策略，用于在温和条件下烯基氟化物与伯、仲和叔烷基卤化物的高效、模块化、不对称氢化和加氢烷基化。该转化提供了从易于获得的起始材料以优异的底物相容性和独特的选择性，容易获得各种结构复杂的仲和叔α-氟酰胺产物的途径。

此外，该方法的实用性通过后期修改和产物衍生得到了证明。研究人员进行了详细的机理研究和DFT计算，表明不对称氢化反应的速率决定步骤是对烯基氟化物的NiH-HAT，立体决定步骤是与Ni烯醇化物的醇配位，然后进行无障碍质子化。该研究还介绍了不对称加氢烷基化反应的机理。

附：英文原文

Title: Selective Hydrofunctionalization of Alkenyl Fluorides Enabled by Nickel-Catalyzed Hydrogen Atoms and Group Transfer: Reaction Development and Mechanistic Study

Author: Fan Chen, Qianwei Zhang, Yingying Li, Zhi-Xiang Yu, Lingling Chu

Issue&Volume: April 15, 2024

Abstract: Due to the unique effect of fluorine atoms, the efficient construction of high-value alkyl fluorides has attracted significant interest in modern drug development. However, enantioselective catalytic strategies for the efficient assembly of highly functionalized chiral C(sp3)-F scaffolds from simple starting materials have been underutilized. Herein, we demonstrate a nickel-catalyzed radical transfer strategy for the efficient, modular, asymmetric hydrogenation and hydroalkylation of alkenyl fluorides with primary, secondary, and tertiary alkyl halides under mild conditions. The transformation provides facile access to various structurally complex secondary and tertiary α-fluoro amide products from readily available starting materials with excellent substrate compatibility and distinct selectivity. Furthermore, the utility of this method is demonstrated by late-stage modifications and product derivatizations. Detailed mechanistic studies and DFT calculations have been conducted, showing that the rate-determining step for asymmetric hydrogenation reaction is NiH-HAT toward alkenyl fluorides and the stereo-determining step is alcohol coordination to Ni-enolates followed by a barrierless protonation. The mechanism for the asymmetric hydroalkylation reaction is also delivered in this investigation.

DOI: 10.1021/jacs.4c01506

Source: https://pubs.acs.org/doi/abs/10.1021/jacs.4c01506