Site-Selective, Copper-Mediated O-Arylation of Carbohydrate Derivatives.

Abstract

Site-selective functionalization of hydroxy groups in sugar derivatives is a major challenge in carbohydrate synthesis. Methods for achieving this goal will provide efficient access to new sugar-derived chemical building blocks and will facilitate the preparation or late-stage modification of complex oligosaccharides for applications in glycobiology research and drug discovery. Here, we describe site-selective, copper-promoted couplings of boronic acids with carbohydrate derivatives. These reactions generate sugar-derived aryl ethers, a structural class that is challenging to generate by other means and has not previously been accessed in a site-selective fashion. Experimental evidence and computational modeling suggest that the formation of a sugar-derived boronic ester intermediate is crucial to the selectivity of these processes, accelerating the arylation of an adjacent hydroxy group. The results demonstrate how the interactions of sugars with boron compounds can be combined with transition metal catalysis to achieve new chemical reactivity.