Synthesis of some new tertiary amines and their application as co-catalysts in combination with L-proline in enantioselective Baylis-Hillman reaction between o-nitrobenzaldehyde and methyl vinyl ketone

A chiral benzodiazepine derivative 1 was synthesized starting from o-nitrobenzoyl chloride and methyl L-prolinate hydrochloride. Diastereomeric (1R,2R,1'S)-(+)-2-[N-methyl-N-(alpha-phenylethyl)amino]cyclohexanol 3a and (1S,2S,1'S)-(+)-2-[N-methyl-N-(alpha-phenylethyl)amino]cyclohexanol 3b were synthesized starting from (S)-alpha-phenylethylamine and cyclohexene oxide via ring-opening, diastereomer separation and N-methylation. (S,S)-octahydrodipyrrolo[1,2-a:1',2'-d]pyrazin 5 was synthesized from methyl L-prolinate. Chiral tertiary amines 1, 3a, 3b and 5 almost cannot catalyze the Baylis-Hillman reaction between o-nitrobenzaldehyde and methyl vinyl ketone (MVK). However, they functioned as efficient catalysts for this reaction in the presence Of L-proline. The corresponding adducts were obtained in good yields with enantioselectivity of 83% ee, 81% ee, 51% ec and 66% ee, respectively. (c) 2006 Elsevier Ltd. All rights reserved.