A mild and convenient method for the synthesis of reverse glycosyl fluorides (RGFs) has been developed that is based on the silver‐promoted radical dehydroxymethylative fluorination of carbohydrates. A salient feature of the reaction is that furanoid and pyranoid carbohydrates furnish structurally diverse RGFs bearing a wide variety of functional groups in good to excellent yields. Intramolecular hydrogen atom transfer experiments revealed that the reaction involves an underexploited radical fluorination that proceeds via β‐fragmentation of sugar‐derived primary alkoxyl radicals. Structurally divergent RGFs were obtained by catalytic C−F bond activation, and our method thus offers a concise and efficient strategy for the synthesis of reverse glycosides by late‐stage diversification of RGFs. The potential of this method is showcased by the preparation and diversification of sotagliflozin, leading to the discovery of a promising SGLT2 inhibitor candidate.

Despite the significant progress in carbohydrate chemistry, there remains a pressing need for efficient and practical glycosylation methods using simple glycosyl donors and with high atom economy. Herein, a new protocol for glycosylation with glycosyl chloride donors under palladium-catalyzed conditions is developed. Pd II complex serves as a Lewis acid to promote the activation of glycosyl chloride for the formation of oxocarbenium ion intermediate. This new method is operationally simple, robust, and enables efficient synthesis of both Oand N-glycosides with a broad substrate scope. In particular, it offers an easy access to a range of N-ribonucleoside analogs.

ince its advent, transition metal-catalysed cross-coupling has revolutionized the art of chemical synthesis [1][2][3][4] . By offering a direct avenue for the union of two or more entities to generate molecular complexity, the field has far-ranging applications across academia and industry 5 . In recent years, the renaissance of non-precious base metal catalysis 6-8 has stimulated remarkable developments in cross-coupling by enabling a broader set of organic precursors to be merged to access new chemical space that is often unattainable by noble-metal-based catalysts 9,10 . In particular, the use of catalysts derived from non-toxic iron, the most abundant and inexpensive transition metal in the Earth's crust [11][12][13] , is naturally appealing to chemists for economic and environmental reasons. Although iron-catalysed cross-coupling 14,15 has seen substantial progress in recent years, the developments in this area and its utility in organic synthesis are still pale in comparison with those of the more established transition metals, such as palladium 16 . This owes, in part, to iron's ability to adopt a large number of oxidation states and spin states 17,18 , which consequently elevates the difficulty of manipulating organoiron chemistry to facilitate C−C bond formation. However, iron-catalysed reactions between two bench-stable electrophilic substrates 19 , which would effectively eliminate the requirement for unstable and basic organometallic reagents 20 , are scarce and underdeveloped.In light of the aforementioned challenges, it is unsurprising that iron catalysis is rarely employed in the context of complex C-glycoside synthesis [21][22][23][24][25][26][27] . Stereochemically pure glycosides with a functionalized alkenyl, alkynyl or heteroaryl substituent on the anomeric carbon play vital roles in various studies that pertain to biological functions 28,29 and diseases 30 (Fig. 1a). These motifs are embedded within the frameworks of countless therapeutically

C-vinyl glycosides are an important class of carbohydrates and pose a unique synthetic challenge. A new strategy has been developed for stereoselective synthesis of Cvinyl glycosides via Pd-catalyzed directed C À H glycosylation of alkenes with glycosyl chloride donors using an easily removable bidentate auxiliary. Both the g C À H bond of allylamines and the d CÀH bond of homoallyl amine substrates can be glycosylated in high efficiency and with excellent regioand stereoselectivity. The resulting C-vinyl glycosides can be further converted to a variety of C-alkyl glycosides with high stereospecificity. These reactions offer a broadly applicable method to streamline the synthesis of complex C-vinyl glycosides from easily accessible starting materials.Scheme 1. Structure and synthesis of C-vinyl glycosides.

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