Transition‐Metal‐Free Methylation of Arylboronates with Tuneable Deuterium Incorporation

Comprehensive Summary The “magic methyl” effect underscores the profound impact of methyl group on improving the pharmacokinetic and pharmacodynamic properties of drug candidates. Conventional methods for methylating arenes, however, predominantly rely on transition‐metal catalysts and frequently lack the versatility for deuteromethylation, a strategy gaining traction for fine‐tuning the metabolic stability of molecules. In this study, we present a transition‐metal‐free methodology for the methylation of arylboronates, which allows for precise control over the degree of deuteration in the introduced methyl group. This method utilizes a commercially available diphenyl sulfonium salt as a methyl source. The proposed process involves the in situ formation of the sulfonium ylide, followed by a Matteson‐type 1,2‐metallate shift for single‐carbon homologation, and ends with a protodeboronation or deuterodeboronation step to reveal the Me group. This one‐pot transformation readily converts aryl‐Bpin compounds into the corresponding CH 3 , CH 2 D, CHD 3 , or CD 3 analogues using readily accessible deuterium sources. By unifying methylation and tunable isotopic labeling in a single, practical operation, this strategy offers a versatile tool for drug discovery and development, enabling substrates beyond the scope of existing methodologies.