Enantioselective synthesis of β-aryl-γ-lactam derivatives via Heck–Matsuda desymmetrization of N-protected 2,5-dihydro-1H-pyrroles

We report herein an enantioselective palladium-catalyzed Heck–Matsuda reaction for the desymmetrization of N -protected 2,5-dihydro-1 H -pyrroles with aryldiazonium salts, using the chiral N , N -ligand ( S )-PyraBox. This strategy has allowed straightforward access to a diversity of 4-aryl-γ-lactams via Heck arylation followed by a sequential Jones oxidation. The overall method displays a broad scope and good enantioselectivity, favoring the ( R ) enantiomer. The applicability of the protocol is highlighted by the efficient enantioselective syntheses of the selective phosphodiesterase-4-inhibitor rolipram and the commercial drug baclofen as hydrochloride.