湖南大学陶忠林团队报道了酮与未活化卤化烷基的催化不对称α-烷基化反应。相关研究成果于2023年12月7日发表在《美国化学会杂志》。

通过在镍催化的C（sp3）–C（sp3）交叉偶联反应中使用α-可烯醇化酮，实现了酮与未活化的卤代烷基直接α-烷基化的催化对映选择性方法。该反应成功的关键在于一种独特的双金属配体。各种无环酮和未活化的烷基碘化物可以在温和的条件下作为合适的底物，以高产率和良好的对映选择性生成具有α-季碳立体中心的手性酮。

研究人员还证明了基于酮部分的一系列转化显示了该方法的潜在应用。初步的机理研究支持双镍催化的交叉偶联机制。

附：英文原文

Title: Catalytic Asymmetric α-Alkylation of Ketones with Unactivated Alkyl Halides

Author: Peigen Wang, Liangwei Zhu, Jingwen Wang, Zhonglin Tao

Issue&Volume: December 7, 2023

Abstract: A catalytic, enantioselective method for direct α-alkylation of ketones with unactivated alkyl halides is realized by employing an α-enolizable ketone in a nickel-catalyzed C(sp3)–C(sp3) cross-coupling reaction. The key to the success is attributed to a unique bimetallic ligand. A variety of acyclic ketones and unactivated alkyl iodides can serve as suitable substrates under mild conditions to generate chiral ketones with α-quaternary carbon stereocenters in high yields with good enantioselectivities. A range of transformations based on the ketone moiety are also demonstrated to show the potential application of this method. Preliminary mechanistic studies support a dinickel-catalyzed cross-coupling mechanism.

DOI: 10.1021/jacs.3c09614

Source: https://pubs.acs.org/doi/abs/10.1021/jacs.3c09614