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Synlett 2008(12): 1809-1812  
DOI: 10.1055/s-2008-1078525
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Practical and Convenient Suzuki-Miyaura Coupling Reaction and α-Arylation Using Diphenylcyclopropylphosphine Ligands

Ken Suzuki*, Tomoya Sawaki, Yoji Hori, Tohru Kobayashi
Takasago International Corporation, Corporate Research & Development Division, 1-4-11 Nishi-yawata, Hiratsuka, Kanagawa 254-0073, Japan
Fax: +81(463)252093; e-Mail: ken_suzuki@takasago.com;
Further Information

Publication History

Received 1 April 2008
Publication Date:
19 June 2008 (online)

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Abstract

A new ligand, diphenylmethylcyclopropylphosphine, has successfully been applied in the palladium-catalyzed Suzuki-Miyaura coupling and α-arylation of ketones with aryl chlorides in moderate to high yields. An asymmetric coupling between anisyl chloride and 2-methylindan-1-one was also tested as the first trial, giving 80% yield and 41% ee with 1 mol% of Pd.

Key words

cross-coupling - halides - ligands - palladium

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As a series of BRIDPs, ligands 1 and 2 are commercially available from Strem Chemicals, Inc. and Sigma-Aldrich.

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For optically pure phosphine 1, it is now under investigation.

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Phosphine ligand 2 was prepared with the same manner as ligand 1, see ref. 15a. ¹H NMR (500 MHz, CDCl3): δ = 0.99-1.40 (m, 11 H), 1.01 (d, J = 1.7 Hz, 3 H), 1.55-1.93 (m, 13 H), 7.00 (t, J = 7.6 Hz, 1 H), 7.07 (t, J = 7.6 Hz, 1 H), 7.12 (t, J = 7.6 Hz, 2 H), 7.19 (d, J = 7.6 Hz, 2 H), 7.28-7.37 (m, 4 H). ¹³C NMR (125 MHz, CDCl3): δ = 20.4 (d, J = 4.4 Hz), 23.9 (d, J = 17.1 Hz), 26.52, 26.54, 27.0 (d, J = 12.6 Hz), 27.36, 27.44 (d, J = 3.9 Hz), 27.9 (d, J = 4.0 Hz), 28.3 (d, J = 15.5 Hz), 29.5, 30.1 (d, J = 8.9 Hz), 31.8 (d, J = 20.1 Hz), 32.7 (d, J = 15.5 Hz), 34.2 (d, J = 25.3 Hz), 34.6 (d, J = 15.8 Hz), 40.6 (d, J = 10.9 Hz), 125.9, 126.1, 127.9, 128.2, 129.8 (d, J = 2.5 Hz), 130.3 (d, J = 1.3 Hz), 143.8 (d, J = 8.8 Hz), 143.9. ³¹P NMR (202 MHz, CDCl3): δ = 11.21. ESI-HRMS: m/z calcd for C28H37P [M + Na]+: 427.2531; found [M + Na]+: 427.2534.

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Optically pure phosphine 2 was prepared by oxidation of phosphine with H2O2, HPLC resolution and the following reduction by Cl3SiH.
Oxidation of Phosphine Ligand 2
H2O2 (30% in H2O, 1.26 g, 11.1 mmol) was added dropwise to a solution of phosphine 2 (3.00 g, 7.42 mmol) in toluene (15 mL) at 0 ˚C. After the mixture was stirred at 35 ˚C for 2 h, an organic phase was separated, washed with 20% aq Na2SO3 and H2O, dried over anhyd MgSO4, and concentrated under reduced pressure to give a crude oxide (3.14 g, quantitative yield) as a white solid. The crude was used for chiral resolution without further purification. ¹H NMR (500 MHz, CDCl3): δ = 1.09 (d, J = 11.8 Hz, 3 H), 1.15-1.32 (m, 7 H), 1.33-2.23 (m, 16 H), 2.52 (dd, J = 4.7, 12.9 Hz, 1 H), 7.07 (t, J = 7.3 Hz, 1 H), 7.14-7.21 (m, 3 H), 7.24-7.32 (m, 2 H), 7.39-7.50 (m, 4 H). ¹³C NMR (125 MHz, CDCl3): δ = 19.9, 20.0, 23.51, 23.53, 23.9, 24.5, 25.36, 25.40, 25.91, 25.95, 25.98, 26.11, 26.12, 26.25, 26.3, 26.6, 26.7, 27.28, 27.34, 27.37, 27.44, 27.53, 27.55, 28.37, 28.39, 35.4, 35.9, 38.8, 39.3, 40.46, 40.48, 126.1, 126.4, 127.6, 128.5, 129.6, 129.9, 141.64, 141.66, 143.4 (observed complexity due to P-C splitting). ³¹P NMR (202 MHz, CDCl3): δ = 49.88. ESI-HRMS: m/z calcd for C28H37PO [M + H]+: 241.2660; found [M + H]+: 241.2656.
HPLC Resolution of Racemic Oxide of Phosphine 2
The optically pure oxide was obtained by HPLC resolution with a Chiralcel OD-H column (250 mm × 20 mm, hexane-2-PrOH = 96:4, flow rate = 10 mL/min).
Reduction of Oxide of Phosphine 2
Under a nitrogen atmosphere, SiCl3H (2.26 g, 16.7 mmol) was added dropwise to a solution of optically pure phosphine oxide (1.00 g, 2.38 mmol) and N,N-dimethylaniline (2.31 g, 19.0 mmol) in xylene (16 mL) at 85 ˚C. After stirring at 115 ˚C for 1.5 h, remaining SiCl3H was removed from the reaction solution by distillation. The solution was washed with 20% aq NaOH and H2O, dried over anhyd MgSO4, and concentrated under reduced pressure. The concentrate was purified by recrystallization from toluene (1.5 mL) and MeOH (6 mL) to give the optically pure phosphine 2 as a white solid (0.49 g, 51%).

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Typical Procedure for the Coupling Reaction of Aryl Halides with Arylboronic Acids
A solution of powdered K2CO3 (2.0 equiv), [(π-allyl)PdCl]2 (0.5 mol%) and ligand (2.0 mol%) in toluene (0.5 M) was stirred for 15 min at r.t. Arylboronic acid (1.5 equiv) and aryl halide (1.0 equiv) were added to the premixed solution. The mixture was stirred at 80 ˚C for the time specified. After cooling to r.t., the reaction solution was diluted with toluene, washed with H2O, dried over MgSO4, and concentrated under reduced pressure. Purification of the concentrate by column chromatography on SiO2 gave the coupling product.
4-Methoxy-4′-methylbiphenyl (Table 1, Entry 3)
Purification by flash chromatography (hexane-toluene = 2:1) gave a white solid. ¹H NMR (300 MHz, CDCl3): δ = 2.38 (s, 3 H), 3.84 (s, 3 H), 6.96 (d, J = 9.0 Hz, 2 H), 7.22 (d, J = 8.0 Hz, 2 H), 7.44 (d, J = 8.0 Hz, 2 H), 7.50 (d, J = 9.0 Hz). ¹³C NMR (75 MHz, CDCl3): δ = 21.0, 55.3, 114.1, 126.6, 127.9, 129.4, 133.7, 136.3, 138.0, 158.9.

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Typical Procedure for the Coupling Reaction of Aryl Halides with Ketones
A solution of NaOt-Bu (1.2 equiv), [(π-allyl)PdCl]2 (0.5 mol%) and ligand (2.0 mol%) in toluene (0.5 M) was stirred for 15 min at r.t. Aryl halide (1.0 equiv) and ketone (1.1 equiv) were added to the solution. The mixture was stirred at 80 ˚C for the time specified. After cooling to r.t., the reaction solution was diluted with toluene, washed with H2O, dried over MgSO4, and concentrated under reduced pressure. Purification of the concentrate by column chromatography on SiO2 gave the coupling product.
2-(4-Methoxyphenyl)propiophenone (Table 1, Entry 7)
Purification by flash chromatography (hexane-EtOAc = 8:1) gave a colorless oil. ¹H NMR (300 MHz, CDCl3): δ = 1.50 (d, J = 6.9 Hz, 3 H), 3.75 (s, 3 H), 4.64 (q, J = 6.9 Hz, 1 H), 6.82 (d, J = 8.7 Hz, 2 H), 7.20 (d, J = 8.7 Hz, 2 H), 7.33-7.41 (m, 2 H), 7.42-7.51 (m, 1 H), 7.90-7.98 (m, 2 H). ¹³C NMR (75 MHz, CDCl3): δ = 19.5, 46.9, 55.2, 114.4, 128.4, 128.7, 128.8, 132.7, 133.5, 136.5, 158.5, 200.5.