Homobenzylic Oxygenation Enabled by Dual Organic Photoredox and Cobalt Catalysis

Abstract

Activation of aliphatic C­(sp3)–H bonds in the presence of more activated benzylic C­(sp3)–H bonds is often a nontrivial, if not impossible task. Herein we show that leveraging the reactivity of benzylic C­(sp3)–H bonds to achieve reactivity at the homobenzylic position can be accomplished using dual organic photoredox/cobalt catalysis. Through a two-part catalytic system, alkyl arenes undergo dehydrogenation followed by an anti-Markovnikov Wacker-type oxidation to grant benzyl ketone products. This formal homobenzylic oxidation is accomplished with high atom economy without the use of directing groups, achieving valuable reactivity that traditionally would require multiple chemical transformations.

A cross-dehydrogenative C(sp3)−H heteroarylation via photo-induced catalytic chlorine radical generation

“…The addition of the so-formed alkyl radical to another equivalent of heteroarene 1-H + followed by hydrogen atom removal would give the desired alkylated heteroarene 3-H + . Meanwhile, to efficiently quench the generated radical intermediate II, a readily accessible cobaloxime catalyst [Co(dmgH) 2 (py)]Cl was introduced to the system [51][52][53][54][55] not only to prevent the over-reduction of intermediate II but also to serve as a terminal oxidant for the rearomatisation of alkylated intermediate III though H 2 evolution.…”

Synthesis of Acridinium Photocatalysts via Site-Selective C–H Alkylation

“…Note that electrolysis in the absence of TEMPO resulted in sluggish conversion. This method demonstrated excellent compatibility with primary (3-10), secondary (11)(12)(13)(14)(15)(16)(17)(18), and tertiary (19)(20)(21)(22) alkylorganotrifluoroborates, providing easy access to acridinium dyes with different steric properties. A highly useful feature of our method is that the monoalkylated product can be alkylated again following the above experimental procedures to furnish novel, 3,6-dialkylated acridinium dyes, using the same (28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45) The alkylation reaction could be scaled up to decagram without difficulty by employing a continuous-flow photochemical reactor 45,46 and a electrochemical batch reactor, as demonstrated in the synthesis of 10.88 g of 36 in 80% yield (Fig.…”

The Merger of Photocatalyzed Hydrogen Atom Transfer with Transition Metal Catalysis for C−H Functionalization of Alkanes and Cycloalkanes

“…In 2020, Nicewicz et al reported a homobenzylic oxygenation reaction achieved by dual organic photoredox and cobalt catalysis (Scheme 13a). [81] The selective oxidation at the homobenzylic positions rather than at the more reactive benzylic positions was achieved in the presence of stoichiometric LiNO 3 as the source of hydrogen atom abstractors. A well-tailored Co II catalyst (36) proved to be more active than the previously reported Co III catalysts (30 and 33).…”