Intramolecular aglycon delivery

The stereoselectivity of these reactions has been shown to be affected by both the nature and the configuration of the protecting group at C-2 on the glycosyl donor ring.

While 1,2-trans-glycosides (e.g. α-mannosides and β-glucosides) can be synthesised easily in the presence of a participating group (such as OAc, or NHAc) at the C-2 position in the glycosyl donor ring, 1,2-cis-glycosides are more difficult to prepare.

However, in this approach, N-iodosuccinimide (NIS) is used to tether the glycosyl acceptor to the enol ether, and in a second step, activation of the anomeric leaving group leads to intramolecular delivery of the aglycon to C-1 and formation of the 1,2-cis-glycoside product.

The allyl group is then isomerized to a prop-1-enyl ether using a rhodium hydride generated from Wilkinson's catalyst ((PPh3)3RhCl) and butyllithium (BuLi).

The resulting enol ether is then treated with NIS and the glycosyl acceptor to generate a mixed acetal.

The anomeric leaving group (Y) is then activated, and the developing oxocarbenium ion is captured by the tethered aglycon alcohol (OR) to give 1,2-cis β-glycoside product.