Catalytic Method for the Synthesis of Deuterium-Labeled <i>N</i>-Heterocyclic Carbenes Enabled by a Coordinatively Unsaturated Ruthenium <i>N</i>-Heterocyclic Carbene Catalyst
Qi Chen, Qing Liu, Jie Xiao, Xuebing Leng, Liang Deng
Abstract
The wide usage of N-heterocyclic carbenes (NHCs) has raised the quest for their deuterated molecules. Effective synthesis method to obtain them, however, has remained elusive. We present here a catalytic method for the preparation of deuterated NHCs, namely, the catalytic hydrogen–deuterium exchange reaction between NHCs and deuterated benzene using a coordinatively unsaturated Ru NHC catalyst. The catalytic system enables selective deuteration of the C(sp3)–H bonds of the alkyl groups on N-substituents, as well as the sterically nonhindered C(sp2)–H bonds of NHCs as demonstrated by the preparation of 16 deuterium-labeled NHCs that have a deuteration ratio on specified sites higher than 90%. The gram-scale synthesis of deuterated IMes indicated the applicability of this catalytic method. Mechanistic studies revealed that the high regio-selectivity toward those C(sp3)–H bonds on NHCs originates from the regio-selectivity of cyclometalation reactions of coordinatively unsaturated Ru NHC species.