Highly selective direct aldol reaction organocatalyzed by (S)-BINAM-L-prolinamide and benzoic acid using α-chalcogen-substituted ketones as donors

Recoverable (S)-BINAM-L-prolinamide in combination with benzoic acid catalyzes and accelerates the direct aldol reaction between several α-chalcogen-substituted ketones and pnitrobenzaldehyde in different solvents, including water. Choosing conveniently the aldol donor, solvent and conditions, it is possible to obtain mainly one of the two possible regioisomers with good diastero- and enantioselectivity. Thus, α-hydroxy and α-alkoxyacetones give mainly syn/anti regioisomers, whereas α-(methylsulphanyl)acetone affords the iso-aldol in 93% ee. In the case of α-hydroxy and α-methoxyacetone the anti diasteromer is obtained with up to 84% ee. However, α-benzyloxyacetone yields mainly the syn-diasteroisomer in 85% ee.This work was financially supported by the Dirección General de Investigación of the Ministerio de Educación y Ciencia of Spain (Grant CTQ2004-00808/BQU), the Generalitat Valenciana (Grant CTIOIB/2002/320, GRUPOS03/134 and GV05/157) and the University of Alicante