Borane- and Silylium-Catalyzed Difunctionalization of Carbohydrates: 3,6-Anhydrosugar Enabled 1,6-Site Selectivity

A novel diastereoselective, Lewis acid catalyzed 1,6difunctionalization of galactose and mannose derivatives has been developed in one pot, via sequential nucleophile additions. Our studies point to the formation of a 3,6-anhydrosugar intermediate as key to the 1,6-site-selectivity. Starting material-specific reactivity occurs when competitive ring-opening C-O cleavage is possible, owed to basicity and stereoelectronic stabilization differences. Lastly, Mayr nucleophilicity parameter values helped predict which reaction conditions would be most suitable for specific nucleophiles.

Automated summary

A novel diastereoselective, Lewis acid catalyzed 1,6-difunctionalization reaction of galactose and mannose derivatives has been developed using sequential nucleophile additions. The formation of a 3,6-anhydrosugar intermediate was found to be crucial for the 1,6-site-selectivity, and the reactivity of starting materials was influenced by the differences in basicity and stereoelectronic stabilization. The nucleophilicity parameter values of Mayr helped in predicting the most suitable reaction conditions for specific nucleophiles.