Direct asymmetric aldol reaction co-catalyzed by L-proline and isothiouronium salts

An efficient, simple, and highly selective protocol for the direct asymmetric aldol reaction between cyclohexanone and aromatic aldehydes using L-proline as a chiral catalyst is reported. Catalytic amounts of achiral isothiouronium iodide salt Id have been used for the first time as a co-catalyst for this reaction, which proved to be an excellent catalyst, producing good to excellent yields (up to 93%) with good stereoselectivities (up to 93:7 dr and 99% ee). These aldols are formed under solvent-free catalytic system, inside a standard laboratory refrigerator, and without stirring. (C) 2014 Elsevier Ltd. All rights reserved.