DBU/H2O: a tunable organocatalytic medium to control the reaction of isophorone with aldehydes at vinylogous aldol addition stage

Abstract

A tunable DBU/H₂O medium was employed to investigate the reaction of isophorone 1 with a variety of aromatic aldehydes 2. One hour mixing of the two components in the medium at room temperature selectively afforded substitution products 3 through activation of the methyl group γ to the carbonyl functionality of isophorone. When the same mixtures were heated at 60 °C for two hours, vinylogous aldol condensation products 4 were obtained instead. This temperature-dependent reactivity demonstrates the switchable behavior of the DBU/H₂O system, allowing precise control over the formation of either aldol addition or condensation products. The versatility of this approach was demonstrated by the synthesis of a wide range of derivatives, highlighting the efficiency and selectivity of this organocatalytic method. Structural characterization of the newly formed compounds was achieved by NMR spectroscopy and single-crystal X-ray diffraction, verifying the proposed molecular architectures. Overall, this work presents DBU/H₂O as a simple, green, and tunable medium to control the selectivity of vinylogous aldol-type reactions in the isophorone system.