Mechanistic Study of the Copper(II)-Mediated Site-Selective O -Arylation of Glycosides with Arylboronic Acids.

Glycosides having multiple free OH groups have been shown to undergo site-selective O -arylations in the presence of arylboronic acids and copper(II) acetate. Herein, a mechanistic analysis of these Chan-Evans-Lam-type couplings is presented based on reaction kinetics, mass spectrometric analysis of reaction mixtures, and substituent effect studies. The results establish that the formation of a substrate-derived boronic ester accelerates the rate-determining transmetalation step. Intramolecular transfer of the aryl group from the boronic ester is ruled out in favor of a pathway in which the key pre-transmetalation assembly is generated from a boronic ester, a copper complex, and a second equivalent of arylboronic acid.