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

Abstract

A chiral benzodiazepine derivative 1 was synthesized starting from o-nitrobenzoyl chloride and methyl l-prolinate hydrochloride. Diastereomeric (1 R,2 R,1′ S)-(+)-2-[ N-methyl- N-(α-phenylethyl)amino]cyclohexanol 3a and (1 S,2 S,1′ S)-(+)-2-[ N-methyl- N-(α-phenylethyl)amino]cyclohexanol 3b were synthesized starting from ( S)-α-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% ee and 66% ee, respectively.