Chiral Squaramides as Hydrogen-Bond Donor Catalysts

Chiral Squaramides as Hydrogen-Bond Donor Catalysts 

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Chiral Squaramides as Hydrogen-Bond Donor Catalysts 253... 

The first report on the development and use of chiral squaramide derivatives as hydrogen-bond donor catalysts appeared in 2008 by Rawal and coworkers [78]. The authors showcased the usefulness of this new scaffold by evaluating the Michael addihon of 1,3-dicarbonyl compounds to nitroalkenes, the same reaction that was used to illustrate the capabilily of a thiourea catalyst by Takemoto [45]. Of the catalysts examined, the cinchonine-derived squaramide 13 functioned well as a bifunctional catalyst and provided the conjugate addition product in high yield and excellent enanhoselectivity (Scheme 10.12). Less reactive substrates such as a-substituted 1,3-dicarbonyl compounds also participate in the desired reaction. 

N-Boc-protected ethyl trifluoropyruvate imine was effectively used in a F-C reaction with indole derivatives for synthesizing, in high selectivities, quaternary a-amino acids via catalysis with chiral phosphoric acid 26e [64]. A binaphthyl-based chiral sulfonimide [42c] and a chiral squaramide-based hydrogen bond donor [42a] were used as effective catalysts for promoting F-C reaction of indoles with imines. Recently, the F-C alkylation of arenes with glyoxylate imine was described via a chiral phosphoric add (Scheme 35.11) [34]. 

A chiral quinine-derived squaramide catalysed the highly enantioselective Michael addition of malononitrile to chalcones. The reactions take place at a very low catalyst loading (0.5 mol%) and provide the Michael adducts with high yields and good enan-tioselectivities (up to 96% ee). Chiral bifunctional squaramides have also been used as multiple hydrogen-bond donor-acceptor organocatalysts for the asymmetric Michael addition of nitroolefins to 1,3-dicarbonyl compounds. ... 

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