Chemoselective Suzuki–Miyaura Coupling of Bromophenyl-Substituted Bromoallenes with Arylboronic Acids

Abstract

Developing highly chemoselective Suzuki–Miyaura coupling reactions is of great value in the synthetic chemistry. Here we report the results of palladium-catalyzed reaction of bromoallenes containing an aryl bromide moiety with arylboronic acids. It is found that the C–Br insertion exclusively takes place on bromoallene rather than on the benzene ring. Theoretical calculations demonstrate that the corresponding oxidative addition intermediate has a much lower free energy.

Key words

coupling - chemoselectivity - palladium - oxidation - addition

• References


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• 16 General Procedure for the Suzuki Reaction A mixture of bromoallene (1.0 mmol), arylboronic acid (1.5 mmol), K₃PO₄·3H₂O (798.9 mg, 3.0 mmol) and Pd(Ph₂PCH₂CO₂)₂ (17.8 mg, 3 mol%) in of THF–H₂O (v/v = 1:1, 3 mL) was stirred at r.t. under nitrogen atmosphere for 6 h. The product was extracted with Et₂O (5 × 5 mL), and the combined organic layer was dried over MgSO₄. Then the solvent was removed under reduced pressure, and the crude product was purified by silica gel column chromatography (eluent: hexane) to afford desired pure product. ¹H NMR and ¹³C NMR spectra were recorded in CDCl₃ solution on a Varian Inova-400 spectrometer (¹H: 400 MHz; ¹³C: 100 MHz). The chemical shifts are reported in ppm downfield from TMS. IR spectra were recorded on a NEXUS FTIR spectrometer. HRMS spectra were recorded on a Q-TOF mass spectrometry (Micromass, England) equipped with Z-spray ionization source. TLC was carried out on SiO₂ (silica gel 60 F254, Merck). Flash chroma-tography was carried out on SiO₂ (silica gel 60, 200–300 mesh). 1-Bromo-4-(3-bromohepta-1,2-dienyl)-benzene (1a) was synthesized following the procedure described in ref. 17. Free energy calculations were carried out using the Gaussian09 program (Frisch, M. J. et al. Gaussian 09, revision A.01). The geometry of each structure was first optimized by density functional theory B3LYP method. The basis set of 6-31+G (d) was used for C, N, and Br atoms, while Pd was described by LANL2DZ basis set and an effective core potential (ECP) employed. Frequency calculations were then performed on each optimized structure, and no imaginary frequency was found, indicating that the stationary point of each structure was minima in the energy surface. Spectral Data for New Compounds 1-Bromo-4-(3-phenylhepta-1,2-dienyl)benzene (3a) Colorless oil. ¹H NMR (400 MHz, CDCl₃): δ = 7.18–7.60 (m, 9 H, ArH), 6.46 (s, 1 H, H–=·=), 2.27–2.57 (m, 2 H, CH₂), 1.47–1.59 (m, 2 H, CH₂), 1.39–1.45 (m, 2 H, CH₂), 0.91 (t, J = 7.2 Hz, 3 H, CH₃). ¹³C NMR (100 MHz, CDCl₃): δ = 206.8, 136.0, 133.9, 132.0, 132.0, 128.7, 128.7, 128.4, 128.4, 127.4, 126.3, 126.3, 120.7, 110.7, 97.2, 30.2, 30.0, 22.8, 14.1. IR (neat): ν = 3059, 2956, 2927, 2858, 1933, 1596, 1486, 1070, 1009, 844, 692 cm^–1. HRMS (EI): m/z calcd for C₁₉H₁₉Br: 326.0670 [M]⁺; found: 326.0669. 1-Bromo-4-(3-p-tolylhepta-1,2-dienyl)benzene (3b) Colorless oil. ¹H NMR (400 MHz, CDCl₃): δ = 7.41 (d, J = 8.4 Hz, 2 H, ArH), 7.31(d, J = 8.0 Hz, 2 H, ArH), 7.19(d, J = 8.4 Hz, 2 H, ArH), 7.13 (d, J = 8.0 Hz, 2 H, ArH), 6.44 (s, 1 H, H–=·=), 2.51–2.56 (m, 2 H, CH₂), 2.33 (s, 3 H, CH₃), 1.53–1.59 (m, 2 H, CH₂), 1.39–1.44 (m, 2 H, CH₂), 0.91 (t, J = 7.6 Hz, 3 H, CH₃). ¹³C NMR (100 MHz, CDCl₃): δ = 206.5, 137.0, 134.0, 132.8, 131.8, 131.8, 129.3, 129.3, 128.2, 128.2, 126.0, 126.0, 120.5, 110.3, 96.9, 30.1, 29.9, 22.6, 21.1, 13.9. IR (neat): ν = 2956, 2923, 2857, 1927, 1647, 1487, 1070, 1010, 846 cm^–1. HRMS (EI): m/z calcd for C₂₀H₂₁Br: 340.0827 [M]⁺; found: 340.0823. 1-Bromo-4-[3-(4-fluorophenyl)hepta-1,2-dienyl]benzene (3c) Colorless oil. ¹H NMR (400 MHz, CDCl₃): δ = 7.36–7.41 (m, 4 H, ArH), 7.17–7.19 (m, 2 H, ArH), 6.98–7.03 (m, 2 H, ArH), 6.46 (br s, 1 H, H–=·=), 2.51–2.54 (m, 2 H, CH₂), 1.55–1.56 (m, 2 H, CH₂), 1.41–1.43 (m, 2 H, CH₂), 0.91 (t, J = 7.2 Hz, 3 H, CH₃). ¹³C NMR (100 MHz, CDCl₃): δ = 206.4, 162.1 (d, J = 246.0 Hz), 133.6, 133.6, 131.8, 131.8, 128.2, 128.2, 127.6 (d, J = 8.0 Hz), 127.6 (d, J = 8.0 Hz), 115.4 (d, J = 22.0 Hz), 115.4 (d, J = 22.0 Hz), 109.7, 97.2, 30.2, 30.2, 22.6, 14.0. IR (neat): ν = 2955, 2927, 2858, 1932, 1600, 1507, 1486, 1230, 1158, 1070, 1009, 845, 835 cm^–1. HRMS (EI): m/z calcd for C₁₉H₁₈FBr: 344.0576 [M]⁺; found: 344.0564. 1-Bromo-4-(3-phenylocta-1,2-dienyl)-benzene (3d) ¹H NMR (400 MHz, CDCl₃): δ = 7.41–7.43 (m, 4 H, ArH), 7.30–7.34 (m, 2 H, ArH), 7.19–7.24 (m, 3 H, ArH), 6.50 (s, 1 H, H–=·=), 2.50–2.51 (m, 2 H, CH₂), 1.50–1.52 (m, 2 H, CH₂), 1.25–1.42 (m, 4 H, CH₂CH₂), 0.86 (t, J = 7.6 Hz, 3 H, CH₃). ¹³C NMR (400 MHz, CDCl₃): δ = 206.7, 135.9, 133.8, 131.8, 131.8, 128.6, 128.6, 128.3, 128.3, 127.2, 126.1, 126.1, 120.6, 110.5, 97.1, 31.8, 30.1, 27.6, 22.5, 14.1. IR (neat): ν = 2950, 2926, 2861, 1925, 1481, 1070, 1014, 8525, 6912 cm^–1. HRMS (EI): m/z calcd for C₂₀H₂₁Br: 340.0815 [M]⁺; found: 340.0827. 1-Bromo-4-(3-p-tolylocta-1,2-dienyl)benzene (3e) Colorless oil. ¹H NMR (400 MHz, CDCl₃): δ = 7.41 (d, J = 6.6 Hz, 2 H, ArH), 7.31 (d, J = 8.0 Hz, 2 H, ArH), 7.19 (d, J = 6.6 Hz, 2 H, ArH), 7.13 (d, J = 8.0 Hz, 2 H, ArH), 6.45 (s, 1 H, H–=·=), 2.50–2.56 (m, 2 H, CH₂), 2.33 (s, 3 H, CH₃), 1.53–1.60 (m, 2 H, CH₂), 1.28–1.39 (m, 4 H, CH₂CH₂), 0.86 (t, J = 7.1 Hz, 3 H, CH₃). ¹³C NMR (100 MHz, CDCl₃): δ = 206.5, 137.0, 134.0, 132.8, 131.7, 131.7, 129.3, 129.3, 128.2, 128.2, 126.0, 126.0, 120.5, 110.3, 96.9, 31.7,30.1, 27.6, 22.5, 21.1, 14.1. IR (neat): ν = 2957, 2923, 2850, 1927, 1524, 1476, 1073, 998, 844, 811 cm^–1. HRMS (EI): m/z calcd for C₂₁H₂₃Br: 354.0975 [M]⁺; found: 354.0983. 1-Bromo-4-[3-(4-fluorophenyl)octa-1,2-dienyl]benzene (3f) Colorless oil. ¹H NMR (400 MHz, CDCl₃): δ = 7.36–7.47 (m, 4 H, ArH), 6.98–7.20 (m, 4 H, ArH), 6.46 (t, J = 3.2 Hz, 1 H, H–=·=), 2.49–2.54 (m, 2 H, CH₂), 1.53–1.60 (m, 2 H, CH₂), 1.28–1.39 (m, 4 H, CH₂CH₂), 0.86 (t, J = 7.1 Hz, 3 H, CH₃). ¹³C NMR (100 MHz, CDCl₃): δ = 206.4, 162.2 (d, J = 245.0 Hz), 131.8, 131.8, 131.7, 131.7, 128.6, 128.6, 127.7 (d, J = 8.0 Hz), 127.7 (d, J = 8.0 Hz), 120.7, 115.3 (d, J = 21.0 Hz), 115.3 (d, J = 21.0 Hz), 109.7, 97.2, 31.7, 30.2, 27.5, 22.5, 14.1. IR (neat): ν = 2957, 2923, 2856, 1927, 1597, 1509, 1228, 1012, 830 cm^–1. HRMS (EI): m/z calcd for C₂₀H₂₀BrF: 358.0732 [M]⁺; found: 357.0659 [M – H]⁺. 1-Bromo-2-(3-phenylhepta-1,2-dienyl)-benzene (3g) ¹H NMR (400 MHz, CDCl₃): δ = 7.31–7.46 (m, 6 H, ArH), 7.19–7.23 (m, 2 H, ArH), 7.03–7.07 (m, 1 H, ArH), 6.98 (t, J = 2.8 Hz, 1 H, H–=·=), 2.54–2.59 (m, 2 H, CH₂), 1.54–1.62 (m, 2 H, CH₂),1.41–1.46 (m, 2 H, CH₂), 0.92 (t, J = 8.0 Hz, 3 H, CH₃). ¹³C NMR (100 MHz, CDCl₃): δ = 207.6, 135.8, 134.1, 133.2, 128.6, 128.6, 128.3, 128.3, 127.5, 127.2, 126.2, 126.2, 122.6, 110.3, 96.7, 30.1, 29.8, 22.7, 14.0. IR (neat): ν = 3059, 2953, 2914, 2860, 1936, 1509, 1476, 1432, 1004, 821, 745, 685 cm^–1. HRMS (EI): m/z calcd for C₁₉H₁₉Br: 326.0667 [M]⁺; found: 326.0670. 1-Bromo-2-(3-p-tolylhepta-1,2-dienyl)benzene (3h) ¹H NMR (400 MHz, CDCl₃): δ = 7.32–7.55 (m, 4 H, ArH), 7.13–7.22 (m, 3 H, ArH), 7.02–7.06 (m, 1 H, ArH), 6.95 (t, J = 2.8 Hz, 1 H, H–=·=), 2.52–2.56 (m, 2 H, CH₂), 2.33 (s, 3 H, CH₃), 1.54–1.60 (m, 2 H, CH₂), 1.38–1.45 (m, 2 H, CH₂), 0.92 (t, J = 7.6 Hz, 3 H, CH₃). ¹³C NMR (100 MHz, CDCl₃): δ = 207.6, 137.1, 134.3, 133.3, 132.8, 129.4, 128.4, 128.4, 128.3, 127.6, 126.2, 126.2, 122.7, 110.3, 96.9, 30.2, 29.9, 22.8, 21.3, 14.1. IR (neat): ν = 3020, 2966, 2925, 2849, 1933, 1516, 1468, 1010, 813, 737, 662 cm^–1. HRMS (EI): m/z calcd for C₂₀H₂₁Br: 340.0829 [M]⁺; found: 340.0827. 1-Bromo-2-[3-(4-fluorophenyl)hepta-1,2-dienyl]benzene (3i) ¹H NMR (400 MHz, CDCl₃): δ = 7.55 (m, 1 H, ArH), 7.38–7.44 (m, 3 H, ArH), 7.19–7.24 (m, 1 H, ArH), 6.99–7.07 (m, 3 H, ArH), 6.97 (t, J = 3.0 Hz, 1 H, H–=·=), 2.51–2.56 (m, 2 H, CH₂), 1.53–1.64 (m, 2 H, CH₂), 1.38–1.47 (m, 2 H, CH₂), 0.92 (t, J = 7.2 Hz, 3 H, CH₃). ¹³C NMR (400 MHz, CDCl₃): δ = 207.4, 162.2 (d, J = 245 Hz), 134.1, 133.4, 131.9, 128.5, 128.4, 127.8 (d, J = 8 Hz), 127.8 (d, J = 8 Hz), 127.7, 122.7, 115.6 (d, J = 10 Hz), 115.6 (d, J = 10 Hz), 109.6, 97.2, 30.2, 27.1, 22.8, 14.1. IR (neat): ν = 3055, 2959, 2918, 2856, 1926, 1605, 1509, 1462, 1168, 1017, 840, 737, 593 cm^–1. HRMS (EI): m/z calcd for C₁₉H₁₈FBr: 344.0570 [M]⁺; found: 344.0576. Compounds 3j,k The products are difficult to purify, and the ¹HNMR data are very complicated, only the typical signal of =·=–H (δ = 6.90, s, 1 H) and ≡–CArHn-Bu (δ = 6.10, s ,1 H) could be assigned
• 17 Du X, Dai Y, He R, Lu S, Bao M. Synth. Commun. 2009; 39: 3940