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

Abstract

The incorporation of C-glycosides in drug design has become a routine practice for medicinal chemists. These naturally occurring building blocks exhibit attractive pharmaceutical profiles, and have become an important target of synthetic efforts in recent decades. Described herein is a practical, scalable, and versatile route for the synthesis of non-anomeric and unexploited C-acyl glycosides through a Ni/photoredox dual catalytic system. By utilizing an organic photocatalyst, a range of glycosyl-based radicals are generated and efficiently coupled with highly functionalized carboxylic acids at room temperature. Distinctive features of this transformation include its mild conditions, impressive compatibility with a wide array of functional groups, and most significantly, preservation of the anomeric carbon: a handle for further, late-stage derivatization.

Synergistic Photoredox/Transition‐Metal Catalysis for Carbon–Carbon Bond Formation Reactions

“…In the last decades, C ‐glycosides gained interest among the medicinal chemistry community as attractive synthetic targets due to their interesting pharmacokinetic and pharmacodynamic properties. Molander and co‐workers focused their interests on C ‐acyl glycosides and their synthesis via a dual photoredox/Ni catalysis pathway under very mild conditions that can preserve the anomeric carbon, a key for late‐stage derivatization (Scheme ) . In this work, the radical precursor is based on the glycosyl moiety bearing a 1,4‐dihydropyridine (DHP) scaffold.…”

“…Molander and co-workers focused their interests on C-acyl glycosides and their synthesis via a dual photoredox/Ni catalysis pathway under very mild conditions that can preserve the anomeric carbon, a key for late-stage derivatization (Scheme 59). [84] In this work, the radical precursor is based on the glycosyl moiety bearing a 1,4-dihydropyridine (DHP) scaffold. The latter can be oxidized by the organic PC and yield the glycosyl radical.…”

Photoredox/Nickel‐Catalyzed Single‐Electron Tsuji–Trost Reaction: Development and Mechanistic Insights

“…During the exploration of various DHPs, heterocyclic (2a and 2e)a nd alkenyl moieties (2c)w ere successfully incorporated within the coupling partners under the optimized reaction conditions.Adesire to integrate greater functional density within the radical precursor led to the exploration of monosaccharide moieties that were recently highlighted in publications from our group. [28] Pleasingly,pyranose DHP afforded the allylated product 2i in high E/Z ratios and diastereoselectivity.…”

A Redox‐Active Nickel Complex that Acts as an Electron Mediator in Photochemical Giese Reactions

“…Thechemical reactivity of excited molecules [3] can then be used to unlock reaction manifolds unavailable to conventional ground-state pathways.I nt his context, our laboratory recently reported [4] how selective excitation with violet light turns 4-alkyl-1,4-dihydropyridines (alkyl-DHPs, 1)into strong reducing agents,w hich can activate reagents by singleelectron transfer (SET) manifolds while undergoing ahomolytic cleavage to generate C(sp 3 )-centered radicals (Figure 1a). [5] This dual photochemical reactivity was used to trigger radical-based CÀCb ond-forming processes.…”