Efficient synthesis of secondary amines by reductive amination of curdlan Staudinger ylides

Abstract

Staudinger-related reactions between azides and phosphines are important in organic chemistry due to their chemoselectivity, high efficiency, and mild reaction conditions. Staudinger reduction of azides affords highly reactive iminophosphorane ylides; the reactivity of the negatively charged ylide nitrogen atom has not previously been fully explored in polysaccharide chemistry. Curdlan, a natural, biocompatible, and bioactive β-1,3-glucan with low toxicity, has remarkable potential in biomedical and pharmaceutical applications. Herein we describe a new method for preparation of regioselectively iminated/aminated curdlan derivatives via a Staudinger ylide. 6-Azido-6-deoxy-2,4-di-O-acyl-curdlan was treated with triphenylphosphine to generate the highly nucleophilic iminophosphorane intermediate which afforded: i) 6-imino curdlans by reaction with several aromatic aldehydes, and ii) 6-monoalkylamino curdlans by reductive amination using these aldehydes and NaBH3CN. This new chemistry combined with our previous results makes available valuable primary, secondary, and tertiary amines, quaternary ammonio derivatives, and amides, all with complete C-6 regioselectivity for the N-substitution.