Nowadays, Cinchona Squaramides have become a dominant core among hydrogen bond catalysts, thanks to their rigid-four-membered ring, the appropriate distance between the donor hydrogens.  A dual hydrogen bond donor moiety in the squaramide, can further increase the catalytic efficiency of Cinchona catalysts by forming additional hydrogen bonds between the catalyst and the substrate during the catalytic process. The squaramide can fix the corresponding substrate and the chiral Cinchona alkaloid skeleton is responsible for the chiral induction.

These alkaloid-based squaramides have found extensive application in several asymmetric catalytic reactions with high yields and extraordinary enantioselectivities.  Such reactions include  Additions, Aldol reaction, Atropisomer synthesis, Bromination, Cascade reactions, Cyclization, Cycloaddition, Friedel-Crafts reaction, Henry reaction, Lactonization, Mannich reaction, Michael Addition, Rauhut-Currier reaction, Spirocyclization, Strecker reaction, Sulfenylation.

Please review the outstanding versatility of these chiral organocatalysts in our free of charge Chiral Catalyst Search Data Base. 

Example from literature

Diastereo- and Enantioselective Michal Addition of 3-Substituted Oxindoles to Trifluoromethyl-Substituted Nitro Olefins Catalyzed by a Cinchona-Alkaloid-Derived Squaramide. (Zhao et al.; Eur. J. Org. Chem. 2014, 3, 644-653.)