Cinchona-Functionalized Crown-Ether-Pinioned Calix[4]arene for a Scalable Asymmetric Organocatalytic Aza-Michael Addition Reaction

We report an enantioselective aza-Michael addition reaction that is organocatalyzed by cinchonine-functionalized crown-ether-strapped calix[4]arene, which yields the aza-Michael adduct in a high yield (99%) with exceptional enantioselectivity (99.8%). The catalyst could be recycled up to 25 test cycles without any significant waning in the yield and selectivity. The synthetic application of this approach to DPP-4 inhibitor drugs, such as (<i>R</i>)-sitagliptin and evogliptin, further demonstrates its feasibility.