Monooxychlorophosphine as a Novel and Efficient Ligand for Palladium-Catalyzed Suzuki-Miyaura Cross-Coupling of Aryl Chlorides

Abstract

A new sterically hindered monooxychlorophosphine was synthesized and the complex generated in situ from its reaction with Pd₂(dba)₃ promoted the Suzuki-Miyaura reactions of arylboronic acids with aryl chlorides in good yields.

Key words

Suzuki reaction - monooxychlorophosphine - aryl chlorides

References and Notes

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• 13a

  
  Synthesis of (2,6- t -Bu ₂ -4-MeC ₆ H ₂ O)PCl ₂ ( 2): To a flame-dried three-necked flask equipped with an addition funnel were added anhyd Et₃N (27 mL, 200 mmol), freshly distilled PCl₃ (26 mL, 300 mmol) and anhyd toluene (200 mL). 2,6-Di-tert-butyl-4-methylphenol (22 g, 100 mmol) dissolved in anhyd toluene (100 mL) was transferred into an addition funnel and was added dropwise to the solution of PCl₃ at 0 °C within one hour. The reaction mixture was stirred for 2 h at r.t. and then for 8 h at 100 °C, after which time the Et₃N·HCl precipitate was isolated by filtration over a celite frit and washed with toluene (3 × 50 mL). The solvent was removed under reduced pressure, and the residual mixture was distilled at 120 °C/0.1 Torr giving 2 as a colorless liquid (70%). ¹H NMR (600 MHz, CDCl₃): δ = 1.46 (s, 18 H), 2.30 (s, 3 H), 7.10 (s, 2 H). ³¹P NMR (242.9 MHz, CDCl₃): δ = 201.9 (s). Anal. Calcd for C₁₅H₂₃OPCl₂: C, 56.09; H, 7.22; P, 9.64. Found: C, 56.02; H, 7.06; P, 9.10

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14

Synthesis of (2,6- t -Bu ₂ -4-MeC ₆ H ₂ O)P(Cl) t -Bu (1): To a flame-dried two-necked flask equipped with an addition funnel were added 2 (1.6 g, 5 mmol) and anhyd Et₂O (50 mL) at 0 °C. t-BuMgCl [7.4 mL (1.7 M/L in THF solution), 12.5 mmol] was transferred into an addition funnel and was added dropwise to the stirred solution within 0.5 h. The ice bath was removed and the stirring was continued at r.t. for 20 h and then the mixture was refluxed for 2 h. The solvent was removed under reduced pressure and the residual mixture was extracted with Et₂O, washed with aq NaHCO₃ (3 × 30 mL) and dried over Na₂SO₄. The solution was filtered and Et₂O was removed and then the residue was recrystallized from absolute ethanol to give 1 as a white solid (83%). ¹H NMR (600 MHz, CDCl₃): δ = 1.32 (d, J = 12 Hz, 9 H), 1.43 (s, 18 H), 2.27 (s, 3 H), 7.03 (s, 2 H). ³¹P NMR (242.9 MHz, CDCl₃): δ = 217.2 (s). Anal. Calcd for C₁₉H₃₂OPCl: C, 66.55; H, 9.41. Found: C, 66.31; H, 8.72. GC-MS: m/z = 342 [M⁺].

15

General Procedure for the Suzuki Reaction: A mixture of aryl chlorides 5a-j (1.5 mmol), arylboronic acid 6a-c (1.7 mmol), Pd₂(dba)₃ (0.0075 mmol), 1 (0.015 mmol), t-BuOK (3 mmol), and THF (5 mL) was added to a flask and stirred at 65 °C under N₂ for the desired time until complete consumption of the starting substrates was observed (as judged by TLC). The solvent was removed under reduced pressure, and the residue was purified by flash column chromatography (PE-EtOAc) to afford the desired coupled products.
Compound 7:^{4a 1}H NMR (400 MHz, CDCl₃): δ = 7.61 (d, J = 8.0 Hz, 4 H), 7.44 (t, J = 7.2 Hz, 4 H), 7.34 (tt, J = 7.2 Hz, J′ = 1.2 Hz, 2 H). ¹³C NMR (150 MHz, CDCl₃): δ = 141.2, 128.7, 127.2, 127.1.
Compound 8:^{9b 1}H NMR (600 MHz, CDCl₃): δ = 7.39 (t, J = 7.2 Hz, 2 H), 7.32 (t, J = 7.2 Hz, 3 H), 7.22-7.25 (m, 4 H), 2.26 (s, 3 H). ¹³C NMR (150 MHz, CDCl₃): δ = 141.9, 135.2, 130.2, 129.7, 129.1, 128.0, 127.2, 126.7, 125.7, 20.4.
Compound 9:^{9b 1}H NMR (600 MHz, CDCl₃): δ = 7.58 (d, J = 7.2 Hz, 2 H), 7.38-7.44 (m, 4 H), 7.34 (t, J = 7.2 Hz, 2 H), 7.17 (d, J = 7.8 Hz, 1 H), 2.42 (s, 3 H). ¹³C NMR (150 MHz, CDCl₃): δ = 141.3, 141.2, 138.2, 128.6, 127.9, 127.1, 124.2, 21.5.
Compound 10:^{16a 1}H NMR (400 MHz, CDCl₃): δ = 7.48 (d, J = 8.0 Hz, 4 H), 7.24 (d, J = 8.0 Hz, 4 H), 2.39 (s, 6 H). ¹³C NMR (150 MHz, CDCl₃): δ = 138.2, 136.6, 129.4, 126.8, 21.1.
Compound 11:^{16b 1}H NMR (300 MHz, CDCl₃): δ = 8.07 (d, J = 6.6 Hz, 2 H), 7.72 (d, J = 6.6 Hz, 2 H), 7.58 (d, J = 6.0 Hz, 2 H), 7.33 (d, J = 9.0 Hz, 2 H), 2.67 (s, 3 H), 2.45 (s, 3 H). ¹³C NMR (150 MHz, CDCl₃): δ = 197.7, 145.7, 138.2, 137.0, 135.6, 129.6, 128.9, 127.1, 126.9, 26.6, 21.1.
Compound 12:^{16c 1}H NMR (600 MHz, CDCl₃): δ = 7.71 (dd, J = 8.4 Hz, J′ = 16.2 Hz, 4 H), 7.5 (d, J = 8.4 Hz, 2 H), 7.29 (d, J = 8.4 Hz, 2 H), 2.41 (s, 3 H). ¹³C NMR (150 MHz, CDCl₃): δ = 145.6, 138.7, 136.3, 132.5, 129.8, 127.4, 127.0, 119.0, 110.5, 21.1.
Compound 13:^{16d 1}H NMR (400 MHz, CDCl₃): δ = 8.84 (d, J = 2.0 Hz, 1 H), 8.57 (d, J = 3.6 Hz, 1 H), 7.87 (dt, J = 8.0 Hz, J′ = 2.0 Hz, 1 H), 7.49 (d, J = 8.0 Hz, 2 H), 7.37 (dd, J = 4.8 Hz, J′ = 3.2 Hz, 1 H), 7.30 (d, J = 8.0 Hz, 2 H), 2.41 (s, 3 H). ¹³C NMR (150 MHz, CDCl₃): δ = 148.1, 148.0, 138.0, 136.6, 134.8, 134.2, 129.8, 126.9, 123.5, 21.1.
Compound 14:^{16b 1}H NMR (400 MHz, CDCl₃): δ = 10.1 (s, 1 H), 7.97 (d, J = 8.4 Hz, 2 H), 7.77 (d, J = 8.4 Hz, 2 H), 7.65 (d, J = 7.2 Hz, 2 H), 7.50 (t, J = 7.2 Hz, 2 H), 7.40-7.43 (m, 1 H). ¹³C NMR (150 MHz, CDCl₃): δ = 191.9, 147.1, 139.7, 135.1, 130.2, 129.0, 128.4, 127.6, 127.3.
Compound 15:^{4a,9b 1}H NMR (400 MHz, CDCl₃): δ = 7.54 (t, J = 8.0 Hz, 4 H), 7.41 (t, J = 7.6 Hz, 2 H), 7.30 (t, J = 7.2 Hz, 1 H), 6.99 (dt, J = 8.8 Hz, J′ = 2.0 Hz, 2 H), 3.85 (s, 3 H). ¹³C NMR (150 MHz, CDCl₃): δ = 159.1, 140.8, 133.8, 128.7, 128.1, 126.7, 126.6, 114.2, 55.3.
Compound 16:^{16e 1}H NMR (300 MHz, CDCl₃): δ = 7.72 (t, J = 7.2 Hz, 8 H), 7.52 (t, J = 7.2 Hz, 4 H), 7.47 (t, J = 7.2 Hz, 2 H). ¹³C NMR (150 MHz, CDCl₃): δ = 140.7, 140.1, 128.8, 127.5, 127.3, 127.0.
Compound 17:^{6e 1}H NMR (400 MHz, CDCl₃): δ = 8.05 (d, J = 8.4 Hz, 2 H), 7.70 (d, J = 8.4 Hz, 2 H), 7.64 (d, J = 7.2 Hz, 2 H), 7.48 (t, J = 7.2 Hz, 2 H), 7.40 (t, J = 7.2 Hz, 1 H), 2.64 (s, 3 H). ¹³C NMR (150 MHz, CDCl₃): δ = 197.7, 145.8, 139.9, 135.8, 128.94, 128.9, 128.2, 127.26, 127.21, 26.7.
Compound 18:^{7f,9b 1}H NMR (400 MHz, CDCl₃): δ = 8.86 (d, J = 0.8 Hz, 1 H), 8.60 (d, J = 4.8 Hz, 1 H), 7.88 (dt, J = 8.0 Hz, J′ = 2.0 Hz, 1 H), 7.59 (d, J = 7.2 Hz, 2 H), 7.48 (t, J = 7.2 Hz, 2 H), 7.42 (d, J = 7.2 Hz, 1 H), 7.34-7.36 (m, 1 H). ¹³C NMR (150 MHz, CDCl₃): δ = 148.4, 148.22, 137.7, 136.6, 134.3, 129.0, 128.0, 127.0, 123.5.
Compound 19:^{16f 1}H NMR (400 MHz, CDCl₃): δ = 8.01 (d, J = 8.0 Hz, 2 H), 7.64 (d, J = 8.0 Hz, 2 H), 7.32-7.39 (m, 2 H), 7.00-7.07 (m, 2 H), 3.85 (s, 3 H), 2.63 (s, 3 H). ¹³C NMR (150 MHz, CDCl₃): δ = 197.8, 156.4, 143.6, 135.5, 130.7, 129.7, 129.4, 128.0, 120.9, 111.3, 55.5, 26.6.