Fe(OTf)3 or Photosensitizer-free blue light activated diazo-thioglycoside donors for Iterative and stereoselective glycosylations.

Abstract

Conventional methods for thioglycoside activation often rely on precious and toxic platinum group metals. Here, we report a catalytic glycosylation strategy employing diazo-thioglycoside donors activated by earth-abundant iron or photosensitizer-free blue light conditions. It confers orthogonal reactivity relative to most glycosyl donors, including widely used thioglycosides and alkyne-based donors, thereby enabling one-pot orthogonal synthesis of glycans. The Thorpe-Ingold-like effect drives the proximity of iron- or blue-light-generated carbenes to the sulfur atom of thioglycosides. This approach accommodates diverse protecting groups and nucleophiles. It applies to various glycosyl donors derived from glucose, mannose, galactose, rhamnose, xylose, lactose, 2-deoxyamino glucose, and furanose derivatives such as ribose and arabinose. Moreover, we demonstrate the robustness of this methodology through challenging 1,2-cis furanosides, late-stage modifications of biomolecules like cholesterol, and the drug simvastatin on a gram scale, along with the iterative synthesis of challenging hexasaccharides.