A Free-Radical Decarboxylative Coupling of Cinnamic Acids with Acetonitrile

Abstract

A copper-catalyzed decarboxylative coupling of cinnamic acids with acetonitrile was developed. By using the free-radical hydrogen-atom-transfer strategy to activate the C–H bond in acetonitrile, a series of nitrile compounds were successfully synthesized. This method uses the common solvent acetonitrile as a source of a nitrile group for introduction into organic molecules, avoiding the use of highly toxic nitriles in conventional nitrile compound syntheses.

Key words

free radicals - C–H bond activation - cinnamic acids - acetonitrile - nitriles - copper catalysis

Publication History

Received: 07 October 2024

Accepted after revision: 11 December 2024

Accepted Manuscript online:
11 December 2024

Article published online:
20 January 2025

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• 10 Allylic Nitriles 1–18; General Procedure A Schlenk tube was charged with the appropriate substrate (0.3 mmol, 1.0 equiv), MeCN (3 mL), TBPB (3.0 equiv), Cu(OAc)₂ (20 mol%), and Na₂CO₃ (1.0 equiv), and the mixture was stirred at 110 °C (oil-bath temperature) until the starting material was consumed (TLC). The mixture was then cooled to r.t., diluted with Et₂O, and washed with brine. The aqueous phase was extracted with Et₂O, and the combined organic extracts were dried (Na₂SO₄) and concentrated in vacuum. The resulting mixture was filtered and concentrated, and the residue was purified by column chromatography (silica gel). 3E-4-Phenylbut-3-enenitrile Purified by column chromatography [silica gel, PE–EtOAc (60:1)] to give a white solid; yield: 22.4 mg (52%); mp 51–53 °C. ¹H NMR (500 MHz, CH₂Cl₂): δ = 7.44–7.20 (m, 5 H), 6.74 (d, J = 15.8 Hz, 1 H), 6.06 (d, J = 15.8 Hz, 1 H), 3.30 (dd, J = 5.6, 1.7 Hz, 2 H). ¹³C NMR (126 MHz, CDCl₃): δ = 135.86, 134.87, 128.93, 128.51, 126.67, 117.49, 116.90, 21.00.