Synthesis of novel chiral (thio)ureas and their application as organocatalysts and ligands in asymmetric synthesis

The synthesis of novel chiral (thio) ureas 1-10 and 14-26 is described. These (thio) ureas incorporate chiral auxiliaries derived from (R)- or (S)-alpha-phenylethylamine, (R)-phenylglycine, or (1R, 2S)-ephedrine. The phenylethyl group in compounds 1-10 and 21-24 adopts a particular orientation in the molecular structure as a consequence of 1,3-allylic strain with the (thio) carbonyl group. Ureas 1-10 were tested as Lewis basic organocatalysts in epoxide ring opening and in aldolic condensation, and it was found that the tetrasubstituted urea (R,R)-2 afforded the best results in terms of reaction yields. (Thio) ureas 20-26 were examined as ligands in the enantioselective diethylzinc addition to benzaldehyde, observing that C-2-symmetric chiral urea (R, S, R, S)-20 provides the expected carbinol in nearly quantitative yield and in up to 62% enantiomeric excess.