Stereoselective strain-release Ferrier rearrangement: the dual role of catalysts†

Abstract

Herein, we report an efficient, stereoselective synthesis of 2,3-unsaturated glycosides under mild conditions through a novel Ferrier rearrangement of reasonably designed glycal donors with C3-position ortho-2,2-dimethoxycarbonycyclopropylbenzoyl (CCBz), facilitated by user-friendly, eco- and environmental-friendly Cu(OTf)₂ or Fe(OTf)₃. The newly devised rearrangement tactic is highly α-stereoselective and applies to a broad scope of nucleophile acceptors, enabling the construction of 2,3-unsaturated O-, S-, N-, and C-glycosides, with exceptional yields and stereoselectivities. DFT calculations were conducted to elucidate the reaction mechanism, unveiling the dual role of the metal catalysts in activating the glycal donor through promoting ring-opening of the intramolecularly incorporated donor–acceptor cyclopropane (DAC) of CCBz and directing the following α-face-preferential nucleophilic attack of the incoming acceptor mediated by H-bond interactions.