Direct C(sp³)–H Cross Coupling Enabled by Catalytic Generation of Chlorine Radicals

Abstract

Here we report the development of a C(sp3)–H cross-coupling platform enabled by the catalytic generation of chlorine radicals by nickel and photoredox catalysis. Aryl chlorides serve as both cross-coupling partners and the chlorine radical source for the α-oxy C(sp3)–H arylation of cyclic and acyclic ethers. Mechanistic studies suggest that photolysis of a Ni(III) aryl chloride intermediate, generated by photoredox-mediated single-electron oxidation, leads to elimination of a chlorine radical in what amounts to the sequential capture of two photons. Arylations of a benzylic C(sp3)–H bond of toluene and a completely unactivated C(sp3)–H bond of cyclohexane demonstrate the broad implications of this manifold for accomplishing numerous C(sp3)–H bond functionalizations under exceptionally mild conditions.

Sulfonamidation of Aryl and Heteroaryl Halides through Photosensitized Nickel Catalysis

“…[10] Moreover, recent reports from the groups of Fu and Peters, Nocera, Molander, and Doyle describing direct photoexcitation of transition-metal catalysts provide elegant demonstrations of this paradigm. [11] Our group has also demonstrated that energy-transfer photosensitization can be used to access triplet excited states of Ni II complexes, specifically in the context of C–O bond formation between carboxylic acids and aryl halides. [10b] A key benefit of this methodology is the separation of light-harvesting and cross-coupling roles between two different transition-metal complexes.…”

Enabling the Cross-Coupling of Tertiary Organoboron Nucleophiles through Radical-Mediated Alkyl Transfer

“…14 Surprisingly, stoichiometric experiments exposing this complex to a variety of oxidant combinations in the presence of alkyltrifluoroborate 13 failed to afford any of the desired coupling product even under prolonged reaction times. The only products observed were THF-adduct 18 (known to be generated under the reaction conditions through C-H abstraction 15 or halide abstraction pathways 16 ) and protodehalogenation. Given these results, it appeared unlikely that the established bipyridyl ligand systems would be broadly applicable to their tertiary counterparts.…”

Mild, Redox‐Neutral Formylation of Aryl Chlorides through the Photocatalytic Generation of Chlorine Radicals

“…Recently, our lab [10] and others reported directing group free Csp 3 –H cross-coupling platforms capable of carrying out C–H arylations at room temperature. In contrast to systems reported by MacMillan [11] and Molander [12] , which primarily employ aryl bromides and iodides, our method utilizes aryl chlorides by design.…”

“…Simultaneously, visible light irradiation of Ir(III) photocatalyst 3 would generate triplet excited *Ir(III) (τ 0 = 2.3 μs, *E 1/2 = 1.21 V vs SCE in MeCN) ( 4 ) which could engage 2 (E P = 0.85 V vs SCE in THF) in photoinduced electron transfer to give presumed Ni(III) intermediate 5 . [10,13] According to our prior studies, [10] photolysis of 5 produces Ni(II) species 6 and a chlorine radical, capable of abstracting a hydrogen atom from 1,3-dioxolane. A concern in developing this reaction was that 1,3-dioxolane has two sets of chemically distinct α-oxy C–H bonds.…”