Iron-Catalyzed Highly Stereospecific Glycosylation with Glycal Epoxides.

Abstract

Complex carbohydrates are essential to understanding life processes, but their synthesis is still challenging. In principle, complex glycans could be rapidly assembled via reiterative and stereospecific glycosylation with glycal epoxides. However, the existing stereospecific glycosylation methods with glycal epoxides are ineffective for the vast majority of secondary sugar acceptors, because they often induce irreversible glycal epoxide decomposition and concurrent SN1-type glycosylation, affording an inseparable mixture of diastereomeric glycosylation products in low yields. We report herein a new catalytic, highly stereospecific glycosylation method for glycal epoxides using readily available iron catalysts. This method is effective for a wide variety of glycal epoxides and glycosyl acceptors, including previously challenging, sterically hindered secondary acceptors and electron-deficient glucuronic ester epoxides. It also facilitates the assembly of an array of biologically important glycosidic linkages that were previously difficult to obtain in high stereoselectivity. Kinetic studies revealed that this iron-catalyzed glycosylation proceeds through SN2-type pathways with both primary and hindered secondary acceptors.