Synthesis of Methyl 4,6-Di-O-ethyl-α-d-glucopyranoside-Based Azacrown Ethers and Their Effects in Asymmetric Reactions

Abstract

Carbohydrate-based crown ethers have been reported to be able to generate asymmetric induction in certain reactions. Previously, it was proved that the monosaccharide unit, the anomeric substituent, and the sidearm could influence the catalytic activity of the monoaza-15-crown-5 macrocycles derived from sugars. In order to gain information about the effect of the flexibility, 4,6-di-O-ethyl-glucoside-based crown compounds were synthesized, and their efficiency was compared to the 4,6-O-benzylidene analogues. It was found that the absence of the two-ring annulation has a negative effect on the enantioselectivity in liquid-liquid two-phase reactions: in the Darzens condensation of 2-chloroacetophenone and in the epoxidation of chalcone. The same trend was observed in the solid-liquid phase Michael addition of diethyl acetamidomalonate. Surprisingly, in the solid-liquid phase cyclopropanation of benzylidenemalononitrile, one of the new catalysts was highly enantioselective (99% ee).