Shenzhen Grubbs Institute and Department of Chemistry, Guangdong Provincial Key Laboratory of Catalysis, Southern University of Science and Technology, Shenzhen518055, China.
Academy for Advanced Interdisciplinary Studies and Department of Chemistry, Southern University of Science and Technology, Shenzhen518055, China.
J Am Chem Soc. 2022 Sep 28;144(38):17319-17329. doi: 10.1021/jacs.2c06718. Epub 2022 Sep 1.
The enantioconvergent cross-coupling of racemic alkyl halides represents a powerful tool for the synthesis of enantioenriched molecules. In this regard, the first-row transition metal catalysis provides a suitable mechanism for stereoconvergence by converting racemic alkyl halides to prochiral radical intermediates owing to their good single-electron transfer ability. In contrast to the noble development of chiral nickel catalyst, copper-catalyzed enantioconvergent radical cross-coupling of alkyl halides is less studied. Besides the enantiocontrol issue, the major challenge arises from the weak reducing capability of copper that slows the reaction initiation. Recently, significant efforts have been dedicated to basic research aimed at developing chiral ligands for copper-catalyzed enantioconvergent radical cross-coupling of racemic alkyl halides. This perspective will discuss the advances in this burgeoning area with particular emphasis on the strategic chiral anionic ligand design to tune the reducing capability of copper for the reaction initiation under thermal conditions from our research group.
外消旋烷基卤化物的对映选择性交叉偶联反应是合成手性富集分子的有力工具。在这方面，第一过渡金属催化通过将外消旋烷基卤化物转化为前手性自由基中间体，为立体收敛提供了合适的机制，因为它们具有良好的单电子转移能力。与手性镍催化剂的发展相比，铜催化的烷基卤化物的对映选择性自由基交叉偶联反应研究较少。除了对映控制问题外，主要的挑战来自铜的还原能力较弱，这会减缓反应的引发。最近，人们致力于开展基础研究，旨在开发用于铜催化的外消旋烷基卤化物的对映选择性自由基交叉偶联反应的手性配体。本文将讨论这一新兴领域的进展，特别强调我们研究小组在战略手性阴离子配体设计方面的进展，以调节铜的还原能力，从而在手热条件下引发反应。
