Cobalt(II)/N,N′,N′′-Trihydroxyisocyanuric Acid Catalyzed Aerobic Oxidative Esterification and Amidation of Aldehydes

A protocol for a Co^II/N,N′,N′′-trihydroxyisocyanuric acid (THICA)-catalyzed aerobic oxidative esterification and amidation of aldehydes has been developed. Preliminary insight into the mechanism indicates that such an oxidative C−O/N cross-coupling reaction proceeds by masking the aldehyde in a nucleophilic addition reaction with an alkoxy/amino source, thereby keeping the highly reactive formyl group from undesired oxidation. This protocol for the oxidative esterification and amidation of aldehydes proceeds through two different pathways that are characterized by the intrinsic nucleophilicity of the alkanol and amine substrates The former occurs in the presence of p-CH₃C₆H₄SO₃H as a cocatalyst and orthoformates as the alkoxy sources, instead of alkanols, to efficiently afford the transient acetals. In contrast, the coupling of the more nucleophilic amines with aldehydes renders a readily accessible cross-coupling reaction that occurs without any cocatalyst but is limited by the potential inhibition of THICA upon nucleophilic substitution by an amine. Consequently, only sterically hindered amines were tolerated in this catalytic system, whereas further condensation occurred in the presence of primary amines to lead to imines.