Site-Specific and Degree-Controlled Alkyl Deuteration via Cu-Catalyzed Redox-Neutral Deacylation

作者：Xukai Zhou, Yu Tingting, Guangbin Dong · 发表于：Journal of the American Chemical Society · 年份：2022 · DOI：10.1021/jacs.2c04382 · 被引用次数：95 · 研究领域：Chemical Reactions and Isotopes、Asymmetric Hydrogenation and Catalysis、Chemical Synthesis and Analysis

Deuterated organic compounds have become increasingly important in many areas; however, it remains challenging to install deuterium site-selectively to unactivated aliphatic positions with control of the degree of deuteration. Here, we report a Cu-catalyzed degree-controlled deacylative deuteration of diverse alkyl groups with the methylketone (acetyl) moiety as a traceless activating group. The use of N -methylpicolino-hydrazonamide (MPHA) promotes efficient aromatization-driven C–C cleavage. Mono-, di-, and trideuteration at specific sites can be selectively achieved. The reaction is redox-neutral with broad functional group tolerance. The utility of this method has been demonstrated in forming a complete set of deuterated ethyl groups, merging with the Diels–Alder reaction, a net devinylative deuteration, and the synthesis of the d 2 -analogue of Austedo.