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

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.