Studies on Direct Stereoselective Aldol Reactions in Aqueous Media

The direct aldol reaction of 4‐nitrobenzaldehyde catalyzed by NaHCO 3 , with three different ketones, Znproline, NaHCO 3 /Znproline, and L ‐proline/Znproline in aqueous media, was studied to explore the selectivity of this environmentally benign type of reaction. Amazingly, NaHCO 3 proper was found to be an efficient catalyst for the selective synthesis of β ‐hydroxy ketones, showing good regio‐ and diastereoselectivity, with all reactions being completed within 9 h. Cyclopentanone and cyclohexanone were found to give rise to reversed diastereoisomer ratios, the syn and anti isomers being the major products, respectively – an unprecedented result. Also, the observed syn diastereoselectivity of aldol reactions catalyzed by L ‐proline and Znproline is remarkable. The corresponding condensation products 7 and 8 were characterized by 1 H‐NMR and single‐crystal X‐ray analyses. Finally, a chelate‐ vs. nonchelate‐type transition state is proposed to account for the differential diastereoselectivities.