Aqueous/Nonaqueous DBU Mixtures: Versatile Switching Media for Chemoselective Aldol, Baylis-Hillman, and Aldol Condensation Reactions

Abstract

Isophorone is a relatively small molecule with several neighboring reacting sites, making it susceptible to various competing reactions with aldehydes, including aldol, Baylis-Hillman (BH), aldol condensation, and Michael addition reactions. In the present work, we have designed a switchable 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU)-catalyzed procedure, where the reaction of isophorone with aldehydes is guided chemoselectively toward either aldol, BH, or aldol condensation reactions, depending on the use of water and/or heat. This controllable divergency likely stems from the ability to tune the dual nucleophilicity/basicity characters of the DBU/H₂O medium. In other words, the nucleophilicity of DBU plays a crucial role in directing the process toward the formation of the BH adducts in the absence of water. At the same time, the aldol pathway dominates when water is present. The conditions were amenable for tandem processes, as demonstrated for an aldol condensation/Diels-Alder sequence.