Cobalt-Catalyzed Dehydrogenative Coupling of Alcohols/Aldehydes and Amines: An Important Role for Imine Hydration

A cobalt and iodide co-catalyzed oxidative amidation reaction between alcohols or aldehydes and amines has been developed. The reactions proceeded smoothly under mild conditions using tert-butyl hydroperoxide solution in water as the terminal oxidant, with broad functional group tolerance. Mechanistic studies indicated that the tBuO/tBuOO radical generated insitu is the active species responsible for hydrogen abstraction in this catalytic process, and not IO^-/IO₂ ^-/IO₃ ^- ions. Investigation into the reaction mechanism also revealed the potential transiency of a hemiaminal and the important role of its regeneration by imine hydration. A good hyd-ing: A protocol for Co^II/I^-/tert-butyl hydroperoxide-catalyzed oxidative cross-coupling of alcohols or aldehydes with amines has been developed. tBuO/tBuOO rather than IO^-/IO₂ ^-/IO₃ ^- is the active hydrogen-abstraction species in this catalytic process. Investigation into the reaction mechanism also revealed the potential transiency of a hemiaminal and the important role of its regeneration by imine hydration.