Radical Dehydroxymethylative Fluorination of Carbohydrates and Divergent Transformations of the Resulting Reverse Glycosyl Fluorides

Abstract

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.

Selective Degradation of Styrene‐Related Plastics Catalyzed by Iron under Visible Light**

“…[24][25][26][27][28][29][30][31][32][33] In addition, CÀ C bond scission of alcohols and ketones through alkoxyl radical intermediates applying inexpensive catalysts were reported recently. [34][35][36][37][38][39][40][41][42][43] Despite limitations, these results illustrate the possibility of developing an economic system for oxidative CÀ C bond cleavage in an environmentally friendly way (Figure 1b). Specially, iron may be a good catalyst candidate, which can perform both CÀ H bond oxidation [25,26,28] and oxidative CÀ C bond cleavage [43] through photocatalysis.…”

Synthesis of C4‐Acyl‐tetrofuranosides and C5‐Acyl‐pentopyranosides Enabled by the Liebeskind‐Srogl Cross‐Coupling Reaction

“…The residue was purified by column chromatography on silica gel with PE/EA/DCM/ MeOH as eluent to give the desired uronic acids 1. [16,24] General Procedure for the Synthesis of thioesters 2 Method A: A round bottom flask was charged with uronic acid 1 (1.0 equiv), thiol (1.5 equiv) in dry DCM (0.1 M) under argon atmosphere. After stirring at 0 °C for 0.5 h, EDC • HCl or DCC (1.5-2.0 equiv) and DMAP (0.1 equiv) were added to the reaction mixture in sequence at 0 °C.…”

“…These studies were mainly focused on thioesters of benzyl-and acetonideprotected glycosyl carboxylic acids and uronic acids, and leaving a room for exploring the Liebeskind-Srogl reaction of the thioesters derived from acyl-protected sugars. In continuation of our interest in synthesis of novel functionalized glycomimetics based on uronic acids, [16] we would like to report the Liebeskind-Srogl cross-coupling reaction of boronic acids with thioesters derived from acyl-protected uronic acids. This reaction enables synthesis of C4-ATFs and C5-APPs with structural diversity and is featured by the configuration retention of the uronic acids.…”

Catalytic generation of alkoxy radicals from unfunctionalized alcohols

“…In 2015, Zhu and coworkers reported a protocol for the ring-opening and fluorination of cyclopropanols and cyclobutanols that relies on a Ag( i ) catalyst, Selectfluor as the fluorinating reagent and oxidant, and a biphasic solvent system ( Scheme 11 ). 50 , 51 These conditions can accommodate electron-rich and electron-deficient tertiary cyclobutanols, furnishing γ-fluorinated ketones, such as thienyl and pyridyl ketones. Additionally, this protocol has been adapted for the ring expansion of cyclobutanol to cyclopentanone and the expansion of a fused bicyclic framework to the corresponding nine-membered fluorinated ketone.…”