Dual catalysis. Merging photoredox with nickel catalysis: coupling of α-carboxyl sp³-carbons with aryl halides

Abstract

Over the past 40 years, transition metal catalysis has enabled bond formation between aryl and olefinic (sp(2)) carbons in a selective and predictable manner with high functional group tolerance. Couplings involving alkyl (sp(3)) carbons have proven more challenging. Here, we demonstrate that the synergistic combination of photoredox catalysis and nickel catalysis provides an alternative cross-coupling paradigm, in which simple and readily available organic molecules can be systematically used as coupling partners. By using this photoredox-metal catalysis approach, we have achieved a direct decarboxylative sp(3)-sp(2) cross-coupling of amino acids, as well as α-O- or phenyl-substituted carboxylic acids, with aryl halides. Moreover, this mode of catalysis can be applied to direct cross-coupling of C(sp³)-H in dimethylaniline with aryl halides via C-H functionalization.

Fig. 1. The merger of photoredox and nickel catalysis yields access to direct sp³-sp² cross-coupling

R, alkyl group.

Fig. 2. Proposed mechanistic pathway of photoredox-nickel-catalyzed decarboxylative arylation

Me, methyl group; L, ligand; Alk, alkyl group.

Fig. 3. Photoredox-nickel catalyzed decarboxylative cross-coupling: aryl halide scope

CFL, compact fluorescent light; Bu, butyl group; Ac, acetyl group.

Fig. 4. Amino acid coupling partners and C_sp³–H, C–X cross-coupling

(A) Evaluation of the amino acid coupling partner in the decarboxylative-arylation protocol. Ac, acetyl group; LED, light-emitting diode. (B) The direct C_sp³–H, C–X cross-coupling via photoredox-nickel catalysis. All yields listed in Figs. 3 and 4 are isolated yields. Reaction conditions for (A) are the same as in Fig. 3. Reaction conditions for (B) are as follows: photocatalyst 1 [1 mole % (mol %)]; NiCl₂·glyme (10 mol %), dtbbpy (15 mol%), KOH (3 equiv.), DMF, 23°C, 26-W light. *Iodoarenes used as aryl halide, X = I. †Bromoarene used, X = Br.