C2-Selective C–H Methylation of Heterocyclic <i>N</i>-Oxides with Sulfonium Ylides
Won Gun An, Su Bin Choi, Nam Hoon Kim, Na Yeon Kwon, Prithwish Ghosh, Sang Hoon Han, Sang Hoon Han, Neeraj Kumar Mishra, Sangil Han, Sangil Han, Sungwoo Hong, In Su Kim
Abstract
A redox-neutral C2-selective methylation of heterocyclic N-oxides with sulfonium ylides is described herein. This report presents unprecedented findings for the utility of sulfonium ylides as the methylation source of N-heterocycles beyond the Corey–Chaykovsky reaction. Intriguingly, pyrrolidine plays a significant role in minimizing the reductive C2-methylation process. This method is characterized by its mild conditions, simplicity, and excellent site selectivity. The applicability of the developed protocol is showcased by the late-stage methylation and sequential transformations of complex drug molecules.