Thiourea organocatalysis


Within the area of organocatalysis, 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 urea. Unlike classical catalysts, these organocatalysts interact by non-covalent interactions, especially hydrogen bonding. The scope of these small-molecule H-bond donors termed urea organocatalysis covers both non-stereoselective and stereoselective applications.

History

Pioneering contributions were made by Kelly, Etter, Jorgensen, Hine, Curran, Göbel, and De Mendoza 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 ring
Hydrogen-bonding between thiourea derivatives and carbonyl substrates involve two hydrogen bonds provided by coplanar amino substituents in the urea.
Squaramides engage in double H-bonding interactions and are often superior to thioureas.

Advantages of thiourea organocatalysts

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 urea catalysts.

Catalysts

A broad variety of monofunctional and bifunctional chiral double hydrogen-bonding urea organocatalysts have been developed to accelerate various synthetically useful organic transformations