Three-Component Palladium-Catalyzed Tandem Suzuki-Miyaura/Allylic Substitution: A Regioselective Synthesis of (2-Arylallyl) Aryl Sulfones

Abstract

A one-pot Pd-catalyzed tandem process to prepare (2-arylallyl) aryl sulfones has been developed. This strategy is based on the modular assembly of a boronic acid, a sodium sulfinate and 2-bromoallyl acetate. The reaction is completely regioselective towards the terminal alkene, yielding (2-arylallyl) aryl (or alkyl) sulfones with yields ranging from 56 to 93%. Control experiments together with DFT calculations allowed to propose a plausible reaction mechanism of the tandem reaction. The usefulness of this methodology has been demonstrated with the formal synthesis of the marketed drug Apremilast and of several natural products by asymmetric hydrogenation. Using the commercially available UbaPHOX iridium complex, chiral ?-methyl sulfones with up to 98% ee were obtained.