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

Carbohydrate-based macrocycles can be enantioselective catalysts in certain reactions. Previously, it was proven that the carbohydrate moiety could affect the catalytic activity of the monoaza-15-crown-5 type macrocycles derived from sugars. According to our experiments so far, the most effective enantioselective catalysts were the D-glucose- and the D-galactose-based crown ethers. To obtain more information about the effect of the carbohydrate unit, a rare monosaccharide, D-idose was incorporated into the monoaza-15-crown-5 structure. The key intermediates were methyl 4,6-O-benzylidene-ff-D-idopyranoside and methyl 4,6-O-benzylidene-beta-D-idopyranoside, which were synthesized from D-galactose. The efficiency of the idopyranoside-based crown compounds synthesized was investigated in asymmetric phase transfer reactions. In liquid-liquid biphasic reactions the highest enantioselectivity was 81% ee, while in solid-liquid phase systems the highest asymmetric induction was 67% ee. It was observed that the enantiodiscrimination was strongly dependent on the configuration of the anomeric center, on the side arm of the nitrogen, and on the structure of the substrate.

Automated summary

Carbohydrate-based macrocycles can serve as enantioselective catalysts, and their catalytic activity can be influenced by the carbohydrate moiety. D-glucose and D-galactose-based crown ethers exhibit the best enantioselective properties. Incorporation of the rare monosaccharide D-idose into the macrocycle structure shows that enantioselectivity is dependent on the configuration of the anomeric center, the side arm of the nitrogen, and the substrate structure.