Synthesis of Reversed C‐Acyl Glycosides through Ni/Photoredox Dual Catalysis

Abstract

The incorporation of C-glycosides in drug design has become ar outine practice for medicinal chemists.T hese naturally occurring building blocks exhibit attractive pharmaceutical profiles,a nd have become an important target of synthetic efforts in recent decades. [1] Described herein is ap ractical, scalable,a nd versatile route for the synthesis of non-anomeric and unexploited C-acyl glycosides through aNi/ photoredox dual catalytic system. By utilizing an organic photocatalyst, arange of glycosyl-based radicals are generated and efficiently coupled with highly functionalizedc arboxylic acids at room temperature.D istinctive features of this transformation include its mild conditions,impressive compatibility with awide arrayoffunctional groups,and most significantly, preservation of the anomeric carbon:ahandle for further,latestage derivatization.Scheme 1. Recent developments in the synthesis of C-acyl glycosides.

From Esters to Ketones via a Photoredox‐Assisted Reductive Acyl Cross‐Coupling Strategy

“…This PARAC process was found to be widely applicable to an array of aryl 2-pyridyl esters regardless of the electronic and steric environments of arenes, even in the presence of more sterically encumbered ortho-substituent (21-22). A variety of functional groups such as F, Cl, Ac, SMe, Bpin, OTBS, OCF 3 were well tolerated (10,11,(13)(14)(15)(16)(17). Importantly, substrates bearing Cl, Bpin functionality provides an additional handle for further elaboration.…”

“…This photoredox-assisted reductive strategy has been quickly applied in nickel-catalyzed CÀC cross-couplings between aryl and alkyl halides. [13] Strikingly, only one isolated example regarding ketones synthesis [14] was recently reported by Amgoune lab [13m] with using N-acyl-imides as acyl donors (Scheme 1 A-3). However, 38-radicals are still incompatible, which remains challenging in cross-coupling reactions for the construction of quaternary carbon centers.…”

Design and synthesis of glycomimetics: Recent advances

“…Recently, Badir et al have proposed the synthesis of “reversed” C‐acyl glycosides, that is, compounds of general formula 136, using a dual‐catalytic Ni/photoredox system that is moderately stereoselective and highly compatible with a vast array of functional groups (Figure ). The starting formylglycosides 137 are easily converted in one step to the 1,4‐dihydropyridines (DHP) 138 , bench‐stable radical precursors that can be used for cross coupling reactions with carboxylic acids 139 activated in situ by dimethyl dicarbonate.…”

“…Dual‐catalytic Ni/photoredox system, leading to the synthesis of “reversed” C ‐acyl glycosides 136 . DMDC, dimethyl dicarbonate…”

Selected Topics in the Syntheses of Bicyclo[1.1.1]Pentane (BCP) Analogues

“…The carboxylic acid 28 can also be converted to the redox‐active ester 51 (72% yield, Scheme ), which could be used subsequently in the decarboxylative functionalization to access methyl 3‐phenylbicyclo[1.1.1]pentane‐1‐carboxylate ( 49 p , 35%, via Fe‐catalysis by Baran), acylation products 49 r (78%, via Ni/photoredox dual catalysis by Molander), 49 s (20%, via N‐heterocyclic carbene catalysis by Ohmiya), and sulfinamide 49 t (75%, via Ni‐catalysis by Baran) …”