N-Heterocyclic Carbene/Carboxylic Acid Co-Catalysis Enables Oxidative Esterification Of Demanding Aldehydes/Enals, At Low Catalyst Loading

We report the discovery that simple carboxylic acids, such as benzoic acid, boost the activity of N-heterocyclic carbene (NHC) catalysts in the oxidative esterification of aldehydes. A simple and efficient protocol for the transformation of a wide range of sterically hindered alpha- and beta-substituted aliphatic aldehydes/enals, catalyzed by a novel and readily accessible N-Mes-/N-2,4,6-trichlorophenyl 1,2,4-triazolium salt, and benzoic acid as co-catalyst, was developed. A whole series of alpha/beta-substituted aliphatic aldehydes/enals hitherto not amenable to NHC-catalyzed esterification could be reacted at typical catalyst loadings of 0.02-1.0 mol %. For benzaldehyde, even 0.005 mol % of NHC catalyst proved sufficient: the lowest value ever achieved in NHC catalysis. Preliminary studies point to carboxylic acid-induced acceleration of acyl transfer from azolium enolate intermediates as the mechanistic basis of the observed effect.