CuI-Catalyzed Cross-Coupling Reaction of (E)-Vinyl Bromides with Nitrogen-Containing Heterocycles

Abstract

An efficient and straightforward copper-catalyzed method allowing vinylation of N-nucleophiles with various substituted (E)-vinyl bromides under palladium-free and ligand-free conditions has taken a high yield (up to 95%). Noteworthy is that the double-bond geometry of these vinyl halides was retained with our protocol.

Key words

halides - nucleophiles - copper - cross-coupling - heterocycles

References and Notes

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• 27c

  Colorless oil. ^¹H NMR (CDCl₃): δ = 7.68 (d, J = 7.2 Hz, 1 H, ArH), 7.30-7.40 (m, 3 H, ArH), 7.06 (d, J = 8.0 Hz, 1 H, CH=CHPh), 6.42 (d, J = 8.0 Hz, 1 H, CH=CHPh).

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25

General Procedure for C-N Coupling Reactions of β-Bromostyrene and Heterocycle Copper(I) iodide (0.1 equiv) and Cs₂CO₃ (2.0 equiv) were added to a screw-capped test tube. The tube was then evacuated and backfilled with argon (3 cycles). N,N-Dimethylformamide (2 mL), nitrogen-containing heterocycles (1.2 equiv; if liquid) and vinyl halide (1.0 equiv; if liquid) were added by syringe at r.t. The tube was again evacuated and backfilled with argon (3 cycles). The mixture was heated to 120 ˚C and stirred for 36-50 h. After cooling to r.t., the mixture was diluted with H₂O, and the combined aqueous phases were extracted three times with EtOAc. The organic layers were combined, dried over Na₂SO₄, and concentrated to yield the crude product, which was further purified by silica gel chromatography, using PE and EtOAc as eluents to provide the desired product.
Characteristic Data of Representative Products Compound 1:^²¹,²² 95%; mp 184-185 ˚C. ^¹H NMR (DMSO-d ₆): δ = 8.02 (s, 1 H, 2-H in imidazole), 7.85 (d, J = 14.4 Hz, 1 H, CH=CHPh), 7.71 (s, 1 H, ArH), 7.26-7.51 (m, 5 H, ArH), 7.05 (s, 1 H, ArH), 7.01-7.05 (m, 2 H, CH=CHPh and ArH). ^¹³C NMR (CDCl₃): δ = 136.1, 134.8, 130.8, 129.4, 128.5, 126.6, 123.1, 119.3, 116.7. HRMS: m/z calcd for C₁₁H₁₀N₂ [M⁺ + H]: 170.0844; found: 170.0843.
Compound 12: 91%; mp 78-80 ˚C. ^¹H NMR (CDCl₃): δ = 7.63 (d, J = 8.0 Hz, 2 H, in ArH), 7.49-7.58 (m, 3 H, in CH=CHPh and ArH), 7.39 (d, J = 8.8 Hz, 2 H, ArH), 7.15-7.30 (m, 2 H, ArH), 6.91 (d, J = 8.8 Hz, 2 H, ArH), 6.64-6.68 (m, 2 H, CH=CHPh and ArH), 3.84 (s, 3 H, CH₃O). ^¹³C NMR (CDCl₃): δ = 159.2, 136.0, 129.5, 129.0, 127.3, 124.3, 123.0, 122.4, 121.6, 121.2, 114. 7, 110.0, 105.3, 55.7. HRMS: m/z calcd for C₁₇H₁₅NO [M⁺ + H]: 249.1154; found: 249.1153.

28

Colorless oil. ^¹H NMR (CDCl₃): δ = 7.48 (s, 1 H, ArH), 7.27-7.29 (m, 3 H, ArH), 7.09-7.12 (m, 2 H, ArH), 7.04 (s, 1 H, ArH), 6.86 (s, 1 H, ArH), 6.74 (d, J = 9.2 Hz, 1 H, CH=CHPh), 6.36 (d, J = 9.2 Hz, 1 H, CH=CHPh). ^¹³C NMR (CDCl₃): δ = 137.4, 134.1, 130.0, 129.1, 128.9, 128.7, 123.8, 122.8, 118.9.