Higher Enantioselectivity with Less Catalyst Loading

Significance

The authors report the intrinsic problem of bifunctional organocatalysts containing acid-base functionalities in one molecule. The enantioselectivity of catalyst 3 for the desymmetrization of anhydride 1 could be increased from 55.5:45.5 er to 97.5:2.5 er by optimizing the reaction conditions. Self-association phenomenon of catalysts 3 and 7 can be prevented by installing a bulky substituent with squaramide catalyst 10. ­Also, the authors attempted to quantify the degree of self-association by DOSY NMR.