Aliphatic C–H Functionalization Using Pyridine N-Oxides as H-Atom Abstraction Agents

Abstract

The alkylation and heteroarylation of unactivated tertiary, secondary, and primary C­(sp3)–H bonds was achieved by employing an acridinium photoredox catalyst along with readily available pyridine N-oxides as hydrogen atom transfer (HAT) precursors under visible light. Oxygen-centered radicals, generated by single-electron oxidation of the N-oxides, are the proposed key intermediates whose reactivity can be easily modified by structural adjustments. A broad range of aliphatic C–H substrates with electron-donating or -withdrawing groups as well as various olefinic radical acceptors and heteroarenes were well tolerated.

Dual-Role Halogen-Bonding-Assisted EDA-SET/HAT Photoreaction System with Phenol Catalyst and Aryl Iodide: Visible-Light-Driven Carbon–Carbon Bond Formation

“…Reactive radical species such as phenyl radicals generated under photoredox catalysis conditions abstract hydrogen atoms from alkanes (hydrogen atom transfer (HAT)) to generate alkyl radicals. , This process allows for the generation of alkyl radicals directly from alkanes instead of using the corresponding radical precursors. We envisioned that HAT reagents could be generated by excitation of EDA complexes in a reaction system that combines EDA-SET and HAT.…”

Visible-light acridinium-based organophotoredox catalysis in late-stage synthetic applications

“…Nicewicz et al 49 reported a highly efficient approach for C–H alkylation reactions with the help of a synergistic combination of an acridinium photoredox catalyst and easily accessible pyridine N -oxides as HAT precursors. The abstraction of tertiary, secondary, and even powerful primary C–H bonds in the presence of electron donating and electron withdrawing moieties is made possible by this entirely organic method.…”

Resurgence and advancement of photochemical hydrogen atom transfer processes in selective alkane functionalizations

“…Remarkably, the HAT catalyst pyridine N-oxide can be easily regenerated from the protonated pyridine N-oxide product through proton transfer, facilitating the turnover of the HAT catalytic cycle. 135,136 Extensive kinetic investigations of t-butyoxyl and cumyoxyl radicals by Bietti and others have revealed various key factors that govern HAT selectivity. 20 Compared to other types of electrophilic open-shell species, alkoxy-radical-mediated C-H functionalizations were once hampered by a dearth of facile routes for direct initiation of these highly reactive species from abundant alcohols.…”

“…Remarkably, the HAT catalyst pyridine N -oxide can be easily regenerated from the protonated pyridine N -oxide product through proton transfer, facilitating the turnover of the HAT catalytic cycle. 135,136…”