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Synlett 2011(16): 2402-2406  
DOI: 10.1055/s-0030-1261223
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Ph2P(O) Group for Protection of Terminal Acetylenes

Xin Yanga, Daisuke Matsuoa, Yoshinori Suzumaa, Jing-Kun Fanga, Feng Xua, Akihiro Orita*a, Junzo Otera*a, Shingo Kajiyamab, Nagatoshi Koumurab,c, Kohjiro Harac
a Department of Applied Chemistry, Okayama University of Science, 1-1 Ridai-cho, Kita-ku, Okayama 700-0005, Japan
Fax: +81(86)2569533; e-Mail: orita@high.ous.ac.jp;
b Graduated School of Pure and Applied Science, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba 305-8571, Japan
c National Institute of Advanced Industrial Science and Technology, Research Center for Photovoltaics, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8565, Japan
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Publication History

Received 30 May 2011
Publication Date:
08 September 2011 (online)

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Abstract

A protecting group Ph2P(O) for terminal ethyne was newly developed. This protecting group can be introduced readily to terminal ethyne by CuI-catalyzed phosphination and subsequent oxidation with H2O2. Ph2P(O)-protected ethynes remained intact in Sonogashira coupling, and their high polarity enabled easy separation of the desired coupling product from by-products. By treatment with t-BuOK, Ph2P(O)-protected ethynes were transformed to the corresponding terminal ethynes.

Key words

alkynes - phosphorylation - protecting groups - coupling

    References and Notes

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12

Synthesis of 15:
(i) Synthesis of 19: To a flask were added 18 (1.51 g, 5.0 mmol), Ph2PCl (0.92 mL, 5.0 mmol), CuI (95.2 mg, 0.5 mmol), toluene (20 mL) and Et3N (1.4 mL), and the mixture was stirred under nitrogen at 80 ˚C for 19 h. After EtOAc had been added, the mixture was filtered, and the filtrate was washed with 10% NH3 (aq) and brine, and dried over Na2SO4. After filtration, the solvents were evaporated, and the crude product was subjected to the next reaction. To a flask were added the crude products, 30% aq H2O2 (5.0 mL) and THF (25 mL) at 0 ˚C, and the mixture was stirred at 0 ˚C for 0.5 h and then at r.t. for 3 h. After workup with CH2Cl2-H2O, the organic layer was washed with brine and dried over Na2SO4. After filtration, the solvents were evaporated and the crude product was subjected to column chromatography on silica gel (Daisogel IR-60-63/210, EtOAc) to give 19 (1.35 g, 54% yield) and 20 (0.83 g, 24% yield). Compound 19: ¹H NMR (300 MHz, CDCl3): δ = 2.81 (s, 1 H), 7.02-7.22 (m, 6 H), 7.31-7.39 (m, 6 H), 7.42-7.46 (m, 2 H), 7.52-7.57 (m, 2 H), 7.70 (d, J = 8.6 Hz, 1 H), 7.79 (d, J = 8.6 Hz, 1 H), 7.95 (q, J = 8.3 Hz, 4 H). ¹³C NMR (100 MHz, CDCl3): δ = 81.55, 82.11, 85.48 (d, J = 169.7 Hz), 104.20 (d, J = 30.5 Hz), 118.30 (d, J = 4.8 Hz), 120.64, 126.21, 126.34, 126.96, 127.23, 127.69, 127.98, 128.13, 128.24 (d, J = 13.6, 13.6 Hz), 128.48, 128.78, 130.21, 130.51 (d, J = 11.5, 11.5 Hz), 131.50, 131.70 (d, J = 2.8, 2.8 Hz), 132.02, 132.22, 132.72, 133.05 (d, J = 121.0, 121.0 Hz), 133.00, 133.82, 139.54, 141.88. HRMS: m/z [M + H+] calcd for C36H24OP: 503.1565; found: 503.1555. Compound 20: ¹H NMR (300 MHz, CDCl3): δ = 6.93-7.01 (m, 4 H), 7.07-7.13 (m, 4 H), 7.19-7.41 (m, 16 H), 7.61 (t, J = 8.2 Hz, 2 H), 7.74 (d, J = 8.6 Hz, 2 H), 7.96 (t, J = 8.9 Hz, 4 H). ¹³C NMR (75 MHz, CDCl3): δ = 86.37 (d, J = 166.8 Hz), 103.25 (d, J = 29.3 Hz), 118.35 (d, J = 4.0 Hz), 126.23, 127.69, 127.99, 128.12, 128.30 (d, J = 13.0, 13.6 Hz), 128.80, 130.03, 130.21 (d, J = 11.7, 11.5 Hz), 131.59, 131.83, 131.87, 132.16, 132.38 (d, J = 120.9, 120.9 Hz), 133.68, 141.04 (d, J = 2.2 Hz). HRMS: m/z [M + H+] calcd for C48H33O2P2: 703.1956; found: 703.1962.
(ii) Synthesis of 21: To a flask were added 19 (1.01 g, 2.0 mmol), 1,3-dibromobenzene (300 mg, 0.91 mmol), Pd(PPh3)4 (104 mg, 0.09 mmol), CuI (17.1 mg, 0.09 mmol), diisopropylamine (5 mL) and toluene (25 mL), and the mixture was stirred under nitrogen at 80 ˚C for 20 h. After workup with EtOAc-H2O, the organic layer was washed with aq NH4Cl and brine, and dried over MgSO4. After filtration, the solvents were evaporated. The crude product was subjected to column chromatography on silica gel (EtOAc) to give 21 (0.96 g, 98% yield) in a pure form. Compound 21: ¹H NMR (500 MHz, CDCl3): δ = 6.48 (s, 1 H), 6.53 (d, J = 7.9 Hz, 2 H), 6.84 (t, J = 7.9 Hz, 1 H), 7.03-7.09 (m, 4 H), 7.11-7.15 (m, 4 H), 7.17-7.26 (m, 8 H), 7.31-7.39 (m, 12 H), 7.45-7.56 (m, 4 H), 7.70 (d, J = 8.3 Hz, 2 H), 7.80 (d, J = 8.6 Hz, 2 H), 7.90 (d, J = 8.3 Hz, 2 H), 7.94-7.97 (m, 6 H). ¹³C NMR (75 MHz, CDCl3): δ = 84.23, 86.49, 91.00 (d, J = 306.0 Hz), 104.29 (d, J = 29.6 Hz), 118.25 (d, J = 4.0 Hz), 121.43, 122.59, 126.15, 126.40, 126.81, 127.17, 127.64, 127.83, 128.11, 128.17 (d, J = 13.3, 13.6 Hz), 128.39, 128.47, 130.17, 130.32 (d, J = 11.8, 11.4 Hz), 130.84, 131.48, 131.65 (d, J = 2.5, 2.5 Hz), 131.77, 132.24, 132.77, 132.82, 132.91 (d, J = 125.9, 125.9 Hz), 133.38, 138.90, 142.08. HRMS: m/z [M + H+] calcd for C78H49O2P2: 1079.3208; found: 1079.3196.
(iii) Synthesis of 22: To a flask were added 21 (534 mg, 0.50 mmol), t-BuOK (167 mg, 1.5 mmol) and THF (10 mL), and the mixture was stirred under nitrogen at r.t. for 15 h. After workup with CH2Cl2-H2O, the organic layer was washed with brine and dried over Na2SO4. After filtration, the solvents were evaporated, and the crude product was subjected to column chromatography on silica gel (hexane-CH2Cl2, 1:1) to give 22 (246 mg, 73% yield) in a pure form. Compound 22: ¹H NMR (300 MHz, CDCl3): δ = 2.79 (s, 2 H), 6.44 (s, 1 H), 6.50 (dd, J = 1.6, 7.8 Hz, 2 H), 6.84 (t, J = 7.5 Hz, 1 H), 7.18-7.33 (m, 8 H), 7.44-7.53 (m, 4 H), 7.74 (d, J = 9.3 Hz, 4 H), 7.94 (q, J = 7.9 Hz, 8 H). ¹³C NMR (75 MHz, CDCl3): δ = 80.79, 82.80, 89.51, 92.67, 120.44, 121.26, 122.99, 126.26, 126.39, 126.55, 126.70, 126.81, 127.70, 128.01, 128.03, 128.05, 128.12, 128.86, 130.73, 132.34, 132.39, 132.90, 133.03, 133.62, 139.90, 140.60.
(iv) Synthesis of 15: To a flask were added 22 (68 mg, 0.1 mmol), 1,3-diiodobenzene (33 mg, 0.1 mmol), Pd(PPh3)4 (12 mg, 0.01 mmol), CuI (2 mg, 0.01 mmol), diisopropyl-amine (5 mL) and toluene (45 mL), and the mixture was stirred under nitrogen at 70 ˚C for 60 h. After workup with CH2Cl2-H2O, the organic layer was washed with aq NH4Cl and brine, and dried over MgSO4. After filtration, the solvents were evaporated. The crude product was subjected to column chromatography on silica gel (hexane-CH2Cl2, 4:1) to give 15 (16 mg, 22% yield) in a pure form as a white powder. Compound 15: ¹H NMR (500 ΜΗz, CDCl3): δ = 6.89-6.95 (m, 6 H), 7.05 (d, J = 8.5 Hz, 4 H), 7.22 (t, J = 7.0 Hz, 4 H), 7.42 (t, J = 7.0 Hz, 4 H), 7.76 (d, J = 8.5 Hz, 4 H), 7.86 (d, J = 8.5 Hz, 4 H), 7.87 (d, J = 8.5 Hz, 4 H), 7.92 (s, 2 H). ¹³C NMR (125 MHz, CDCl3): δ = 90.4, 92.1, 121.8, 123.6, 126.4, 126.7, 126.8, 128.1, 128.2, 129.2, 129.6, 132.7, 133.0, 136.9, 138.6.