Copper(I) Iodide-Catalyzed (Het)arylation of Diethyl Malonate with (Het)aryl Bromides by Using 1,3-Benzoxazole as a Ligand

Abstract

An efficient Ullmann-type coupling of aryl bromides with diethyl malonate in the presence of copper(I) iodide and 1,3-benzoxazole is presented. This method has a broad substrate scope (heterocyclic and phenyl bromides) and good functional-group tolerance (OMe, Me, Ac, CN, NO₂, F, and Cl). Moreover, less time is needed to reach full conversion (3–9 hours).

Key words

Ullmann coupling - benzoxazole - copper catalysis - aryl ­bromides - hetarylation - arylation

• References and Notes

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• 15 Diethyl (Het)arylmalonates 3a–v; General Procedure DMSO (2 mL), the appropriate (het)aryl bromide 1 (1.0 mmol), diethyl malonate (2; 1.5 mmol), CuI (0.1 mmol), 1,3-benzo­xazole (0.2 mmol), and K₃PO₄ (3 mmol) were successively added to a sealed tube under argon. The mixture was stirred at 50 °C for 3–9 h until the reaction was complete (TLC) and then poured into sat. aq NH₄Cl (20 mL). The mixture was extracted with EtOAc (3 × 20 mL), and the organic phases were combined and washed with sat. aq NH₄Cl (2 × 20 mL) and H₂O (2 × 20 mL). The separated organic layer was then dried (Na₂SO₄), filtered, and concentrated under reduced pressure. The residue was purified by chromatography (silica gel, hexane/EtOAc). Diethyl Pyridin-3-ylmalonate (3a) Purified by column chromatography [silica gel, hexane/EtOAc (6:1)] to give a yellowish oil; yield: 204 mg (86%). ¹H NMR (400 MHz, CDCl₃): δ = 8.55–8.51 (m, 2 H), 7.80 (dt, J = 8.0, 2.0 Hz, 1 H), 7.27 (dd, J = 7.9, 4.8 Hz, 1 H), 4.59 (s, 1 H), 4.24–4.11 (m, 4 H), 1.21 (t, J = 7.1 Hz, 6 H). ¹³C NMR (101 MHz, CDCl₃): δ = 167.43, 150.28, 149.53, 136.93, 128.97, 123.52, 62.19, 55.43, 13.97. HRMS (TOF): m/z [M + H]⁺ calcd for C₁₂H₁₅NO₄: 238.1074; found: 238.1084.