Acylation of trans-2-substituted cyclohexanols: Reversal of diastereoselectivity depends on scaffold substitution and achiral amine catalyst

We report progress in the investigation of previously observed amine-induced changes in diastereoselectivity during acylations of several chiral templates. The presence of simple achiral amines during acylation of racemic trans-1,2-substituted cyclohexanols with racemic 2-chloro-propionyl chloride affected the diastereomeric ratio (dr) of the products. The linear load-dependence on the dr in the case of pyridine and DMAP led to reversal of diastereoselectivity overall. The reaction kinetics were investigated by NMR spectroscopy, and computational results supporting a proposed mechanism are presented