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).

d-Idose-Based Monoaza-15-Crown-5 Lariat Ethers: Synthesis of an Elusive d-Hexose and Application of Derived Macrocycles in Enantioselective Syntheses

“…In the past few decades, a multitude of carbohydrate-based crown ethers have been synthesized by our research group. In terms of enantioselectivity the most effective catalysts in our experiments so far were the D-glucose- [8] and the D-galactose-based [9] crown ethers. It has been described previously [9] that the selectivity depends on several factors: Apart from the chemical structure of the lariat ether's R group shown in Figure 1 and the protecting groups that are attached to the carbohydrate backbone, the most important factor is the conformation and the absolute configuration of the sugar moiety.…”

“…In terms of enantioselectivity the most effective catalysts in our experiments so far were the D-glucose- [8] and the D-galactose-based [9] crown ethers. It has been described previously [9] that the selectivity depends on several factors: Apart from the chemical structure of the lariat ether's R group shown in Figure 1 and the protecting groups that are attached to the carbohydrate backbone, the most important factor is the conformation and the absolute configuration of the sugar moiety. We considered using less studied and infrequent monosaccharides to prepare azacrown ethers to expand the pool of experimental data.…”