Palladium-Catalyzed Direct α-Arylation of p-Methoxybenzyl-Protected S,S-Dimethylsulfoximine

Sulfoximines have recently gained considerable recognition as an important structural motif in the life sciences. This is especially true for (hetero)aryl-substituted S,S-dimethylsulfoximine derivatives, such as the marketed insecticide sulfoxaflor, as well as the clinical candidates­ PTEFb inhibitor BAY 1143572 and ATR inhibitor AZD 6738 for the treatment of cancer. Herein, the first palladium-catalyzed direct α-arylation of p-methoxybenzyl-protected S,S-dimethylsulfoximine using readily available (hetero)aryl bromides is reported. This new method provides a safe, short, and efficient approach to (hetero)aryl-substituted­ S,S-dimethylsulfoximine derivatives, an important class of bioactive compounds, demonstrated by application of this methodology to an improved synthesis of PTEFb inhibitor BAY 1143572.