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

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.