Photoinduced Site-Selective Functionalization of Aliphatic C–H Bonds by Pyridine N-oxide Based HAT Catalysts

Abstract

Readily available and facilely tunable pyridine N-oxides have been developed as effective photoinduced hydrogen-atom-transfer (HAT) catalysts for site-selective C–H functionalizations of a broad range of C–H substrates, including unactivated alkanes. Pyridine N-oxide radicals, catalytically generated from N-oxides by photoredox catalyzed single-electron oxidation, are the key intermediates that enable an effective HAT process for carbon radical generation to achieve alkylation, amination, azidation, allylation, and cyanation. Additionally, the fine-tuning of reactivity and selectivity of pyridine N-oxides through operationally simple structural modification was investigated and showed promising capability for selective functionalization of unactivated C­(sp3)–H bonds.

Iron-Catalyzed C(Sp3)–H Borylation, Thiolation, and Sulfinylation Enabled by Photoinduced Ligand-to-Metal Charge Transfer

“…Halogen (Cl, Br)-containing compounds were also found to be suitable substrates ( 72 – 78 ), with the observation of a minor dehalogenative borylation product (usually <10% yield). Unlike other radical-mediated C­(sp 3 )–H functionalizations of adamantane, for which the HAT process usually occurred at the tertiary C–H bond, our method showed that the methylene C–H bond was preferentially borylated ( 79 ). Ethyl-, isopropyl-, and tert -butylbenzene were borylated with complete regioselectivity for the methyl groups over both benzylic and aromatic C–H bonds ( 80 – 83 ).…”

An iron-catalyzed C–S bond-forming reaction of carboxylic acids and hydrocarbons via photo-induced ligand to metal charge transfer

“…It is noteworthy that adamantane reacts with thiosulfonate in an unconventionally regioselective manner. 21 Furthermore, C(sp 3 )–H thiolation took place exclusively at the β-carbon atoms of 3-pentanone, resulting in the desired product in 34% yield ( 81 ). Direct C–H thiolation can also be applied to ethers and amides ( 82 and 83 ).…”

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…”