Palladium-Catalyzed Reaction of Arenediazonium Tetrafluoroborates with Methyl 4-Hydroxy-2-butenoate: An Approach to 4-Aryl Butenolides and an Expeditious Synthesis of Rubrolide E

The palladium-catalyzed reaction of arenediazonium tetrafluoroborates with methyl 4-hydroxy-2-butenoate in MeOH under mild conditions gives 4-arylbutenolides usually in good to high yields through a domino vinylic substitution/cyclization process. The reaction tolerates a variety of useful substituents including the whole range of halogen substituents, nitro, ether, cyano, keto, and ester groups and can be performed as a one-pot process generating the arenediazonium salt in situ. By using this method, the marine antibiotic rubrolide E has been synthesized via an expeditious and efficient sequential protocol that omits the isolation of the butenolide intermediate (two operative steps, 52% overall yield).