Alkyl Carbon-Carbon Bond Formation by Nickel/Photoredox Cross-Coupling

Abstract

The union of photoredox and nickel catalysis has resulted in a renaissance in radical chemistry as well as in the use of nickel-catalyzed transformations, specifically for carbon-carbon bond formation. Collectively, these advances address the longstanding challenge of late-stage cross-coupling of functionalized alkyl fragments. Empowered by the notion that photocatalytically generated alkyl radicals readily undergo capture by Ni complexes, wholly new feedstocks for cross-coupling have been realized. Herein, we highlight recent developments in several types of alkyl cross-couplings that are accessible exclusively through this approach.

Keywords: alkyl radicals; cross-coupling; nickel; photocatalysis; single-electron transmetalation.

Figure 1

Common photocatalysts for Ni/photoredox dual cross-coupling

Figure 2

Photocatalyst excitation and quenching cycles. [PC] = photocatalyst.

Figure 3

General mechanism of Ni/photoredox dual catalytic cycle

Figure 4

Pathways for hydrogen atom transfer.

Figure 5

Net reductive Ni/photoredox cross-coupling cycle.

Scheme 1.

Cross-coupling of tertiary alkyl fragments.^[] DMA = N,N-dimethylacetamide

Scheme 2.

Alkyl-aryl cross-coupling using carboxylic acids. DME = 1,2-dimethoxyethane. dtbbpy = 4,4′-di-tert-butyl-2,2′-dipyridyl. DMF = N,N-dimethylformamide. CFL = compact fluorescent light. LED = light emitting diode. dFppy = 2-(2,4-difluorophenyl)pyridine. THP = tetrahydropyran. DMSO = dimethyl sulfoxide.

Scheme 3.

Alkyl-aryl cross-coupling using potassium and ammonium silicates. [Si] = bis(catecholato)silicate. COD = 1,5-cyclooctadiene. phen = 1,10-phenanthroline.

Scheme 4.

Alkyl-aryl cross-coupling using 1,4-dihydropyridines. ppy = 2-phenylpyridine. DMI = 1,3-dimethyl-2-imidazolidinone. bpy = 2,2’-bipyridine dMeObpy = 4–4′-dimethoxy-2–2′-bipyridine.

Scheme 5.

Desymmetrization of meso-anhydrides to effect acyl-alkyl cross-coupling.^[c]

Scheme 6.

C(sp³)–C(sp³) cross-couplings.