We report an enantioselective aza-Michael addition reaction that is organocatalyzed by cinchonine-functionalized crown-ether-strapped calix4arene, 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 (R)-sitagliptin and evogliptin, further demonstrates its feasibility.
Antil et al. (Mon,) studied this question.