Selective palladium-catalyzed functionalization of α-methylene butanolides

We describe an efficient and selective functionalization of α-methylene-γ-butyrolactone. The two-step sequence involves the preparation of bromomethylene butyrolactone 2 in good yield prior to a palladium-catalyzed coupling process. The latter allowed the installation of aryl, alkenyl, and alkynyl groups under Suzuki-Miyaura, Heck, and Sonogashira cross-coupling conditions. The reaction sequences involving Pd(dppf)Cl2-CsF, Pd(OAc)2-PPh3-Ag2CO3, Pd(PPh4)4-CuI-Et3N as the corresponding catalytic systems allow the preparation of an unprecedented panel of α-unsaturated substituted butyrolactones 4–16 ranging from moderate to excellent yields. In all cases, the E-configuration of the exo-double bond is retained from the starting materials to the targets, regardless of the nature of the substituent introduced.