Glycosyl Exchange of Unactivated Glycosidic Bonds: Suppressing or Embracing Side Reactivity in Catalytic Glycosylations

Abstract

While developing boron-catalyzed glycosylations using glycosyl fluoride donors and trialkylsilyl ether acceptors, competing pathways involving productive glycosylation or glycosyl exchange were observed. Experimental and computational mechanistic studies suggest a novel mode of reactivity where a dioxolenium ion is a key intermediate that promotes both pathways through addition to either a silyl ether or to the acetal of an existing glycosidic linkage. Modifications in catalyst structure enable either pathway to be favored, and with this understanding, improved multicomponent iterative couplings and glycosyl exchange processes were demonstrated.

Glycosyl Exchange of Unactivated Glycosidic Bonds: Suppressing or Embracing Side Reactivity in Catalytic Glycosylations

“…Herein, we study an alternate reaction pathway for chemical glycosylations of sterically hindered or weak nucleophiles, involving the direct activation of glycosidic C–O bonds and their replacement with a different glycoside . Through a combined computational and experimental approach, we provide evidence that this process occurs via the direct insertion of a weakly coordinated dioxolenium into an existing glycosidic bond to provide a new glycosidic bond.…”