Synthesis of a New N-Diaminophosphoryl-N′-[(2S)-2-pyrrolidinylmethyl]thiourea as a Chiral Organocatalyst for the Stereoselective Michael Addition of Cyclohexanone to Nitrostyrenes and Chalcones - Application in Cascade Processes for the Synthesis of Polycyclic Systems

A highly diastereoselective and enantioselective Michael addition of enolizable ketones such as cyclohexanone and acetophenone to a variety of substituted trans-beta-nitrostyrenes and chalcones was catalyzed by a novel chiral and unsymmetrical thiourea as organocatalyst in the presence of water or under neat reaction conditions. The anticipated Michael adducts, gamma-nitrocarbonyl adducts and 1,5-dicarbonyl derivatives, were obtained in up to 98:2 diastereomeric ratio and up to 96 % enantiomeric excess. The application of this new chiral organocatalyst was extended to an asymmetric Michael addition-proton transfer-aldol reaction cascade process, a formal [3+3] cyclization reaction of cyclohexanone with arylidenepyruvates, with high stereoselectivity. The organocatalyst reported here is one of the very few able to promote the above cascade process, providing the important bicyclic framework that is found in many natural products.