Asymmetric 1,3-Dipolar Cycloaddition Reactions of Azomethine Imines with Acrolein Catalyzed by L-Proline and Its Derivatives

Abstract

1,3-Dipolar cycloadditions between acrolein and various N,N'-cyclic azomethine imines in the presence of L-proline and its derivatives as organocatalysts were investigated. Reactions that were catalyzed by (S)-indline-2-carboxylic acid (30 mol%) in CHCl 3 /MeOH 97:3 (v/v) showed high exo-selectivities (exo/endo 91:9 ∼ 99:1) and enantioselectivities (75 ∼ 98% ee). In contrast, reactions catalyzed by L-proline (30 mol%) under similar conditions favored the endo-cycloadduct (83:27 ∼ 99:1) with modest to good enantioselectivities (31 ∼ 83% ee). Based on our studies, the diastereoselective mechanism of the L-proline-catalyzed reaction was found to involve the isomerization of the exo- to the endo-cycloadduct in the presence of L-proline.