Thiourea organocatalysis

Within the area of organocatalysis, (thio)urea organocatalysis describes the use of ureas and thioureas to accelerate and stereochemically alter organic transformations. The effects arise through hydrogen-bonding interactions between the substrate and the (thio)urea. Unlike classical catalysts, these organocatalysts interact by non-covalent interactions, especially hydrogen bonding ('partial protonation'). The scope of these small-molecule H-bond donors termed (thio)urea organocatalysis covers both non-stereoselective and stereoselective applications. 1998: Jacobsen's chiral (polymer-bound) Schiff base thiourea derivative for asymmetric Strecker reactions.2003: Takemoto's bifunctional chiral thiourea derivative, catalysis of asymmetric Michael- and Aza-Henry reactions.2004: Nagasawa's chiral bis-thiourea organocatalyst, catalysis of asymmetric Baylis-Hillman reactions.2005: Nagasawa's bifunctional thiourea functionalized guanidine, asymmetric catalysis of Henry(Nitroaldol)reactions.2005: Ricci's chiral thiourea derivative with additional hydroxy-group, enantioselective Friedel-Crafts alkylation of indols with nitroalkenes.2005: Wei Wang's bifunctional binaphthyl-thiourea derivative, asymmetric catalysis of Morita-Baylis-Hillman reactions.2005: Soos's, Connon and Dobson's bifunctional thiourea functionalized Cinchona alkaloid, asymmetric additions of nitroalkanes to chalcones as well as malonates to nitroalkenes 2006: Yong Tang's chiral bifunctional pyrrolidine-thiourea, enantioselective Michael additions of cyclohexanone to nitroolefins.2006': Berkessel's chiral isophoronediamine-derived bisthiourea derivative, catalysis of asymmetric Morita-Baylis-Hillman reactions.2006: Takemoto's PEG-bound chiral thiourea, asymmetric catalysis of (tandem-) Michael reactions of trans-β-nitrostyrene, aza-Henry reactions.2007: Kotke/Schreiner, polystyrene-bound, recoverable and reusable thiourea derivative for organocatalytic tetrahydropyranylation of alcohols.2007: Wanka/Schreiner, chiral peptidic adamantane-based thiourea, catalysis of Morita-Baylis-Hillman reactions.2007: Takemoto's chelating bifunctional hydroxy-thiourea for enantioselective Petasis-type reaction of quinolines.2007: Ma Jun-An's Chiral Bifunctional Primary and tertiary Amine-thiourea Catalysts Based on Saccharides. Within the area of organocatalysis, (thio)urea organocatalysis describes the use of ureas and thioureas to accelerate and stereochemically alter organic transformations. The effects arise through hydrogen-bonding interactions between the substrate and the (thio)urea. Unlike classical catalysts, these organocatalysts interact by non-covalent interactions, especially hydrogen bonding ('partial protonation'). The scope of these small-molecule H-bond donors termed (thio)urea organocatalysis covers both non-stereoselective and stereoselective applications. Pioneering contributions were made by Kelly, Etter, Jorgensen, Hine, Curran, Göbel, and De Mendoza (see review articles cited below) on hydrogen bonding interactions of small, metal-free compounds with electron-rich binding sites. Peter R. Schreiner and co-workers identified and introduced electron-poor thiourea derivatives as hydrogen-bonding organocatalysts. Schreiner's thiourea, N,N'-bis[[3,5-bis(trifluormethyl)phenyl thiourea, combines all structural features for double H-bonding mediated organocatalysis: Hydrogen-bonding between thiourea derivatives and carbonyl substrates involve two hydrogen bonds provided by coplanar amino substituents in the (thio)urea. Squaramides engage in double H-bonding interactions and are often superior to thioureas. Thio)ureas are green and sustainable catalysts. When effective, they can offer these advantages: H-bond accepting substrates include carbonyl compounds, imines, nitroalkenes. The Diels-Alder reaction is one process that can benefit from (thio)urea catalysts.