New Phosphine-Functionalized N-Heterocyclic Carbene Ligands for Palladium-Catalyzed Hydroarylation Reaction

Abstract

Novel triarylphosphine-functionalized imidazolinium salts have been prepared and successfully applied in palladium-­catalyzed hydroarylation of bicyclic olefins. Under reductive conditions (HCOOH, Et₃N), the complexes generated in situ from imidazolinium salts and Pd(OAc)₂ catalyzed the hydroarylation of bicyclic alkenes with aryl iodides, providing the hydroarylation products with high turnover numbers (TON, up to 1.9·10⁵) and ­turnover frequencies (TOF, up to 6.3·10⁴).

Key words

bicyclic alkene - functionalized phosphine ligand - ­hydroarylation - N-heterocyclic carbene - palladium

References and Notes

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9

Physical Data of Amide 5.
White solid, mp 94-96 °C. ¹H NMR (300 MHz, CDCl₃): δ = 1.41 (s, 9 H, CH₃), 6.88 (m, 1 H, Ar-H), 6.92 (t, J = 7.2 Hz, 1H, Ar-H), 7.26-7.36 (m, 12 H, Ar-H, NH), 7.93 (dd, J = 8.1, 4.5 Hz, 1 H, Ar-H). ¹³C NMR (75 MHz, CDCl₃): δ = 28.2, 80.4, 120.6, 123.6, 125.0, 125.2, 128.7, 128.8, 129.1, 130.4, 133.5, 133.7, 134.1, 134.9, 135.0, 141.7, 142.0, 152.9. ³¹P NMR (121 MHz, CDCl₃): δ = -21.2. MS (ESI): m/z = 378 [M + 1]. Anal. Calcd for C₂₃H₂₄NO₂P: C, 73.19; H, 6.41; N, 3.71. Found: C, 73.01; H, 6.26; N, 3.68.

10

Physical Data.
Compound 6a: oil. ¹H NMR (300 MHz, CDCl₃): δ = 1.09 (s, 9 H, CH₃), 3.12 (m, 1 H, NCH₂), 3.21 (m, 1 H, NCH₂), 3.40 (m, 1 H, NCH₂), 4.25 (br s, 2 H, NCH₂, NH), 6.44 (d, J = 8.1 Hz, 2 H, Ar-H), 6.58 (t, J = 7.2 Hz, 1 H, Ar-H), 6.93-7.22 (m, 16 H, Ar-H). ¹³C NMR (75 MHz, CDCl₃): δ = 27.8, 42.5, 49.0, 49.1, 79.9, 112.1, 116.6, 127.4, 128.1, 128.2, 128.3, 128.4, 128.9, 129.6, 129.7, 133.4, 133.6, 133.7, 134.9, 136.0, 136.1, 136.7, 136.8, 145.8, 146.2, 148.0. ³¹P NMR (121 MHz, CDCl₃): δ = -17.9. HRMS (ESI): m/z calcd for C₃₁H₃₄N₂O₂P: 497.2352; found: 497.2359.
Compound 6b: white solid, mp 92-93 °C. ¹H NMR (300 MHz, CDCl₃): δ = 1.16 (s, 9 H, CH₃), 2.18 (s, 6 H, CH₃), 2.21 (s, 3 H, CH₃), 3.01-3.35 (m, 4 H, NCH₂), 4.18 (br s, 1 H, NH), 6.78 (s, 2 H, Ar-H), 7.03 (m, 1 H, Ar-H), 7.15-7.31 (m, 13 H, Ar-H). ¹³C NMR (75 MHz, CDCl₃): δ = 18.7, 20.6, 28.1, 47.2, 50.8, 80.0, 127.7, 128.4, 128.5, 128.6, 128.8, 129.5, 130.5, 133.7, 134.0, 135.3, 136.4, 136.6, 137.1, 137.2, 143.8, 146.5, 146.9, 155.5. ³¹P NMR (121 MHz, CDCl₃): δ = -18.2. MS (ESI): m/z = 539 [M + 1]. Anal. Calcd for C₃₄H₃₉N₂O₂P: C, 75.81; H, 7.30; N, 5.20. Found: C, 75.71; H, 7.16; N, 5.25.
Compound 6c: oil. ¹H NMR (300 MHz, CDCl₃): δ = 1.15 (s, 9 H, CH₃), 1.19 (d, J = 5.4 Hz, 12H, CH₃), 2.97 (m, 1 H, NCH₂), 3.21 (m, 4 H, NCH₂, CH), 3.45 (m, 1 H, NCH₂), 4.29 (br s, 1 H, NH), 7.05 (m, 4 H, Ar-H), 7.23-7.32 (m, 13 H, Ar-H). ¹³C NMR (75 MHz, CDCl₃): δ = 24.4, 24.5, 27.9, 28.2, 50.2, 50.9, 76.9, 77.2, 50.9, 80.1, 123.7, 127.8, 128.6, 128.7, 128.8, 128.9, 130.0, 130.2, 133.9, 134.0, 134.1, 135.4. ³¹P NMR (121 MHz, CDCl₃): δ = -17.1. HRMS (ESI): m/z calcd for C₃₇H₄₆N₂O₂P: 581.3291; found: 581.3297.

11

Physical Data. Compound 7a: white foam. ¹H NMR (300 MHz, CDCl₃): δ = 3.83 (s, 2 H, NCH₂), 3.89 (s, 2 H, NCH₂), 6.98 (s, 2 H, Ar-H), 7.17-7.37 (m, 15 H, Ar-H), 7.71 (s, 2 H, Ar-H). ¹³C NMR (75 MHz, CDCl₃): δ = 49.5, 50.3, 123.6, 128.8, 128.9, 129.1, 129.2, 129.5, 129.8, 130.2, 130.3, 130.6, 130.9, 131.0, 131.6, 133.9, 134.1, 135.7, 136.1. ³¹P NMR (121 MHz, CDCl₃): δ = -18.6. HRMS (ESI): m/z calcd for C₂₆H₂₆N₂P: 397.1828; found: 397.1834.
Compound 7b: white foam. ¹H NMR (300 MHz, CDCl₃): δ = 2.23 (s, 3 H, CH₃), 2.48 (s, 6 H, CH₃), 3.87 (m, 2 H, NCH₂), 4.21 (m, 2 H, NCH₂), 6.80 (s, 2 H, Ar-H), 7.22 (m, 2 H, Ar-H), 7.37-7.65 (m, 12 H, Ar-H). 8.56 (br s, 2 H), 10.84 (br s, 2 H). ¹³C NMR (75 MHz, CDCl₃): δ = 19.0, 19.1, 20.7, 44.3, 48.2, 118.6, 118.7, 123.3, 124.1, 129.1, 129.2, 130.8, 131.0, 132.1, 133.3, 133.8, 134.0, 135.9, 139.2, 145.6, 145.7, 145.9. ³¹P NMR (121 MHz, CDCl₃): δ = -17.9. MS (ESI): m/z = 439 [M - 2 HCl + 1]. Anal. Calcd for C₂₉H₃₃Cl₂N₂P: C, 68.10; H, 6.50; N, 5.48. Found: C, 68.07; H, 6.68; N, 5.56.
Compound 7c: white foam. ¹H NMR (300 MHz, CDCl₃): δ = 1.19 (d, J = 6.0 Hz, 6 H, CH₃), 1.32 (d, J = 6.0 Hz, 6 H, CH₃), 3.37 (m, 1 H, NCH₂), 3.47 (m, 2 H, NCH₂), 3.57 (m, 2 H, CH), 4.04 (m, 1 H, NCH₂), 4.23 (m, 1 H, NCH₂), 6.66 (t, J = 7.2 Hz, 1 H, Ar-H), 6.78 (m, 2 H, Ar-H), 7.14-7.40 (m, 14 H, Ar-H), 10.90 (br s, 4 H). ¹³C NMR (75 MHz, CDCl₃): δ = 23.9, 27.3, 27.4, 36.5, 38.7, 50.8, 52.8, 109.8, 117.5, 119.0, 119.1, 123.2, 124.6, 124.7, 127.5, 127.6, 127.8, 128.5, 128.7, 128.9, 129.0, 129.9, 132.6, 132.8, 133.9, 134.1, 134.2, 142.2, 142.4, 148.2, 148.4. ³¹P NMR (121 MHz, CDCl₃): δ = -22.5. HRMS (ESI): m/z calcd for C₃₂H₃₆N₂P: 481.2767; found: 481.2770.

12

Physical Data. Compound 2a: white solid, mp 235-237 °C. ¹H NMR (300 MHz, CDCl₃): δ = 4.50 (s, 4 H, NCH₂), 6.90 (m, J = 6.8, 4.0 Hz, 1 H, Ar-H), 7.25-7.45 (m, 17 H, Ar-H), 8.17 (dd, J = 7.6, 4.0 Hz, 1 H, Ar-H), 8.85 (s, 1 H, NCH). ¹³C NMR (75 MHz, CDCl₃): δ = 49.8, 52.9, 119.3, 127.9, 128.9, 129.4, 130.1, 130.2, 130.6, 131.3, 133.9, 134.2, 134.3, 134.5, 135.4, 135.5, 135.7, 138.5, 138.7, 155.6. ³¹P NMR (121 MHz, CDCl₃): δ = -14.6. HRMS (ESI): m/z calcd for C₂₇H₂₄N₂P: 407.1593; found: 407.1593.
Compound 2b: white solid, mp 255-257 °C. ¹H NMR (300 MHz, CDCl₃): δ = 2.28 (s, 3 H, CH₃), 2.36 (s, 6 H, CH₃), 4.40 (m, 2 H, NCH₂), 4.83 (m, 2 H, NCH₂), 6.89 (m, 3 H, Ar-H), 7.25 (m, 4 H, Ar-H), 7.40 (m, 7 H, Ar-H), 7.58 (m, 1 H, Ar-H), 8.13 (s, 1 H, NCH), 8.53 (m, J = 7.8, 4.5 Hz, 1 H, Ar-H). ¹³C NMR (75 MHz, CDCl₃): δ = 18.1, 18.2, 18.3, 21.0, 52.0, 53.7, 53.8, 119.0, 129.2, 129.3, 129.9, 130.5, 131.7, 133.7, 133.9, 134.4, 135.5, 140.5, 158.1, 158.2. ³¹P NMR (121 MHz, CDCl₃): δ = -18.1. MS (ESI): m/z = 449 [M - Cl]. Anal. Calcd for C₃₀H₃₀ClN₂P: C, 74.29; H, 6.23; N, 5.78. Found: C, 74.32; H, 6.38; N, 5.80.
Compound 2c: white solid, mp 268-270 °C. ¹H NMR (300 MHz, CDCl₃): δ = 1.28 (d, J = 6.6 Hz, 6 H, CH₃), 1.32 (d, J = 6.6 Hz, 6 H, CH₃), 3.35 (m, 2 H, CH), 4.39 (m, 2 H, NCH₂), 4.80 (m, 2 H, NCH₂), 6.95 (dd, J = 7.5, 3.6 Hz, 1 H, Ar-H), 7.21-7.28 (m, 6 H, Ar-H), 7.36-7.48 (m, 8 H, Ar-H), 7.60 (t, J = 7.5 Hz, 1 H), 8.13 (s, 1 H, NCH), 8.53 (dd, J = 7.8, 4.5 Hz, Ar-H). ¹³C NMR (75 MHz, CDCl₃): δ = 24.6, 25.2, 28.5, 53.9, 54.6, 125.0, 128.8, 129.1, 129.2, 129.3, 129.6, 130.0, 130.5, 131.2, 131.8, 133.5, 133.6, 133.9, 134.1, 134.2, 134.4, 138.7, 139.0, 146.8, 157.4, 157.5. ³¹P NMR (121 MHz, CDCl₃): δ = -18.6. HRMS (ESI): m/z calcd for C₃₃H₃₆N₂P: 491.2611; found: 491.2606.

14

General Experimental Procedure.
Under an atmosphere of nitrogen, 5.0 mL DMSO were injected to a Schlenk tube charged with Pd(OAc)₂ (0.01 mmol), imidazolinium salt 2 (0.01 mmol) and t-BuOK (0.01 mmol). The mixture was stirred at r.t. for 2 h. An appropriate amount of this catalyst solution was taken and added to the solution of iodobenzene (204 mg, 1 mmol), norbornene (320 mg, 3.4 mmol), Et₃N (379 mg, 3.75 mmol) and formic acid (138 mg, 3 mmol) in 5.0 mL of DMSO. The mixture was stirred at 120 °C, and the course of reaction was monitored by GC. After the starting material was completely consumed the reaction mixture was cooled to r.t., and 50 mL of H₂O was added. The product was extracted with pentane (3 × 30 mL), and the extract was dried over anhyd Na₂SO₄. The product was purified by column chromatography on silica gel eluting with PE.

18

Catalyst loading for the reaction of 13c is 0.5 mol%.