Design and Synthesis of Oxazoline-Based Scaffolds for Hybrid Lewis Acid/Lewis Base Catalysis of Carbon–Carbon Bond Formation

A new class of hybrid Lewis acid/Lewis base catalysts has been designed and prepared with an initial objective of promoting stereoselective direct aldol reactions. Several scaffolds were synthesized that contain amine moieties capable of enamine catalysis, connected to heterocyclic metal-chelating sections composed of an oxazole–oxazoline or thiazole–oxazoline. Early screening results have identified oxa­zole–oxazoline-based systems capable of promoting a highly diastereo- and enantioselective direct aldol reaction of propionaldehyde with 4-nitrobenzaldehyde, when combined with Lewis acids such as zinc triflate.