title: Origin of the superior performance of (thio)squaramides over (thio)ureas in organocatalysis.
abstract: The Diels-Alder cycloaddition of anthracene and nitrostyrene catalyzed by the squaramide-derived aminocatalysts (Sq) recently reported by Jørgensen and co-workers (Angew. Chem. 2012, 124, 10417; Angew. Chem. Int. Ed. 2012, 51, 10271) has been studied by using modern tools of computational quantum chemistry. This catalyst is compared with analogous urea-, thiourea-, and thiosquaramide-derived aminocatalysts. Ultimately, a thiosquar-amide-derived catalyst is predicted to result in the lowest free-energy barrier, while retaining the same high degree of enantioselectivity as Sq. This stems in part from the superior hydrogen-bonding ability of thiosquaramides, compared to squaramides and (thio)ureas. We also examine the hydrogen-bonding ability of (thio)ureas and (thio)-squaramides in model complexes. In contrast to previous work, we show that aromaticity does not contribute significantly to the enhanced hydrogen-bonding interactions of squaramides. Overall, thiosquaramide, which has not been explored in the context of either organocatalysis or molecular recognition, is predicted to lead to strong, co-planar hydrogen bonds, and should serve as a potent hydrogen-bonding element in a myriad of applications.
authors.affiliation: Department of Chemistry, Texas A&M University, College Station, TX 77842 (USA), Fax: (+1) 979-845-4719.
authors.forename: Tongxiang
authors.initials: T
authors.lastname: Lu
authors.forename: Steven E
authors.initials: SE
authors.lastname: Wheeler
keywords: Diels-Alder reactions; bifunctional catalysts; density functional calculations; organocatalysis