A palladium/Et3N·HI-catalyzed highly selective 7-endo alkyl-Heck-type reaction of epoxides and a DFT study on the mechanism

Abstract

A highly efficient 7-endo alkyl-Heck reaction was achieved via palladium catalyzed ring-opening of epoxides, providing a variety of 6-aryl-2,3,4,7-tetrahydro-1H-azepin-3-ols and 6-aryl-2,3,4,5-tetrahydrooxepin-3-ols. Pd(PPh₃)₄, a catalytic amount of Et₃N·HI and an additional ligand L4 are essential for this transformation. The methodology showed a broad substrate scope with excellent 7-endo selectivity. Preliminary mechanistic investigations provide evidence for the generation of alkyl radicals, indicating a hybrid palladium-radical process. DFT studies revealed that the C–C bond formation process proceeds through a rate-limiting concerted “epoxy ring opening and C–C coupling” step, which leads to a diradical species as a key resting state. A plausible mechanism initiated by an in situ generated HPd(II)I species is proposed based on the preliminary exploration by experiments and DFT calculations.