Mediator-Enabled Electrocatalysis with Ligandless Copper for Anaerobic Chan–Lam Coupling Reactions

Abstract

Simple copper salts serve as catalysts to effect C–X bond-forming reactions in some of the most utilized transformations in synthesis, including the oxidative coupling of aryl boronic acids and amines. However, these Chan–Lam coupling reactions have historically relied on chemical oxidants that limit their applicability beyond small-scale synthesis. Despite the success of replacing strong chemical oxidants with electrochemistry for a variety of metal-catalyzed processes, electrooxidative reactions with ligandless copper catalysts are plagued by slow electron-transfer kinetics, irreversible copper plating, and competitive substrate oxidation. Herein, we report the implementation of substoichiometric quantities of redox mediators to address limitations to Cu-catalyzed electrosynthesis. Mechanistic studies reveal that mediators serve multiple roles by (i) rapidly oxidizing low-valent Cu intermediates, (ii) stripping Cu metal from the cathode to regenerate the catalyst and reveal the active Pt surface for proton reduction, and (iii) providing anodic overcharge protection to prevent substrate oxidation. This strategy is applied to Chan–Lam coupling of aryl-, heteroaryl-, and alkylamines with arylboronic acids in the absence of chemical oxidants. Couplings under these electrochemical conditions occur with higher yields and shorter reaction times than conventional reactions in air and provide complementary substrate reactivity.

Light-Promoted Low-Valent-Tungsten-Catalyzed Ambient Temperature Amination of Boronic Acids with Nitroaromatics

“…1 4-Fluoro-N-phenylaniline (3d). 22 Column chromatography (petroleum ether/dichloromethane = 100:1 to 30:1; silica gel, 100−200 mesh); colorless liquid (30.3 mg, 81% yield). 1 H NMR (400 MHz, chloroform-d) δ 7.18 (dd, J = 8.6, 7.4 Hz, 2H), 6.97 (dd, J = 9.1, 4.8 Hz, 2H), 6.94−6.87 (m, 4H), 6.85−6.80 (m, 1H), 5.50 (br s, 1H).…”

“…1 Methyl 4-(Phenylamino)benzoate (3g). 22 Column chromatography (petroleum ether/dichloromethane = 100:1 to 30:1; silica gel, 100−200 mesh); colorless liquid (29.5 mg, 65% yield). 1 4-(Phenylamino)benzaldehyde (3h).…”

Enabling room-temperature reductive C–N coupling of nitroarenes: combining homogeneous and heterogeneous synergetic catalyses mediated by light

“…Chief among them include homogeneous catalysis, such as the palladium-catalyzed Buchwald-Hartwig reaction, which enables the net redoxneutral nucleophilic substitution of an aryl halide with N-nucleophiles via Pd(0)/Pd(II) activation by oxidative addition. [3][4][5][6][7] In alternative strategies, the copper-catalyzed Ullmann reaction [8][9][10][11][12] and the Chan-Lam reaction [13][14][15] have been established for the construction of the C-N bond in an oxidative manner by the reaction of N-nucleophiles with aryl boron reagents under aerobic copper catalysis (Scheme 1A). However, all well-known strategies adopt primary amines as nitrogen sources, which are always derived from nitroarenes by stoichiometric reduction.…”

Three copper(II) complexes derived from 2‐methylquinoline and cyclic secondary amines: Synthesis and catalytic application in C—N bond forming reactions

“…[ 17 ] Soon after, copper‐catalyzed anaerobic Chan–Lam reaction between arylboronic acids and various amines with electrochemistry in replace of strong chemical oxidants was also achieved by Sevov's group. [ 18 ] Very recently, Di et al documented the coupling of 2‐aminopyridine and arylboronic acid to furnish N ‐arylpyridin‐2‐amine derivatives via irradiation of blue light using copper modified phosphorus‐doped g‐C 3 N 4 (Cu/P‐CN) as a heterogeneous photocatalyst. [ 19 ] Despite these important advances, the exploitation of new methodology to achieve copper‐catalyzed Chan–Lam reaction is an essential and challenging issue.…”