Palladium-Catalyzed α-Arylation of Meyers’ Chiral Bicyclic Lactams and a Deprotonative Ring-Opening Sideline

Described is a deprotonative α-arylation reaction of Meyers’ chiral bicyclic lactams (MCBLs) under palladium catalysis, and a substrate-dependent post-transformation. When the bridgehead carbon of the MCBLs is substituted with a methyl or an ethyl group, the initial arylation product undergoes a further rearrangement reaction to give a conjugated framework. On the other hand, the substrates bearing a bridgehead-isopropyl or an aryl group are converted into the corresponding exo-arylation products. Preliminary studies indicated that the rearrangement pathway was promoted by deprotonation and was independent of palladium catalysis. In addition to mechanistic interests, this study demonstrates a modular and divergent synthesis of functionalized lactams.