Selective Methylation of Amides, N‑Heterocycles, Thiols, and Alcohols with Tetramethylammonium Fluoride

We herein disclose the use of tetramethylammonium fluoride (TMAF) as a direct and selective methylating agent of a variety of amides, indoles, pyrroles, imidazoles, alcohols, and thiols. The method is characterized by operational simplicity, wide scope, and ease of purification. Our computational studies suggest a concerted methylation–deprotonation as the preferred reaction pathway.