Cinchona cinchonine-derived squaramide

As described above, cinchona-based (thio)ureas have proven to be highly efficient H-bond donor catalysts. In 2008, Rawal and coworkers developed a highly promising new family of cinchona-based H-bond donor catalysts such as 157 by replacing the thiourea moiety of cinchona-based thiourea catalysts with the squaramide unit [47]. The squaramide moiety of 157 is able to form two H-bonds to a reactant due to the more accessible reaction site and fixed syn-orientation of the NH-protons. Using only 0.5 mol% of the cinchonine-derived squaramide catalyst 157, various Michael donors 158 and nitroalkenes 130 were smoothly converted to the desired adducts 159 in excellent yield and ee values (up to 99% ee) (Scheme 9.54). 

Rawal and coworkers prepared a squaramide derivative of cinchonine (30) and proved this cinchona alkaloid analog to be an efficient catalyst for the conjugate addition of 2,4-pentadione to P-nitrostyrene [59] (Scheme 6.39). With sub-shtuted 2,4-pentadiones, the diastereoselectivity was low, except for the methyl ester of 2-oxocyclopentanecarboxylic acid, which gave rise to a raho of 50 1 for the diastereoisomers. 

The extension of the thiourea-tertiary amine concept to the cinchona alkaloids was reported by several groups independently in 2005. The general usefulness of cinchona alkaloids as bifunctional catalysts was recognized by several groups even before this date [9]. The focus herein is on (thio)urea and squaramide catalysts since they are prototypes of more efficient catalysts. The Chen and the Dixon groups screened cinchonine and cinchonidine-derived thiourea catalysts for conjugate... 

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