An Alkyne Metathesis-Based Route to ortho-Dehydrobenzannulenes

Abstract

An application of alkyne metathesis to 1,2-di(prop-1-ynyl)arenes, producing dehydrobenzannulenes, is described. An efficient method for selective Sonogashira couplings of bromoiodoarenes under conditions of microwave irradiation is also reported.

Key words

alkyne metathesis - 1,2-di(prop-1-ynyl)arenes - dehydrobenzannulenes - microwave irradiation - Sonogashira coupling

References

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• 11f

  1,2-Dibromo-4,5-diiodobenzene (5e) was prepared using the general procedure described for 5j. Compound 5e: White needles (33%), mp 173-175 °C. ¹H NMR (400 MHz, CDCl₃): δ = 8.03 (s, 2 H). ¹³C NMR (100 MHz, CDCl₃): δ = 142.5, 125.4, 106.9. MS (EI, 70 eV): m/z (%) = 488 (100) [M⁺], 361 (32), 234 (17), 153 (8), 74 (20). IR (CS₂): 2925, 1408, 1282, 1005, 877 cm^-1. HRMS: Calcd for C₆H₂Br₂I₂: 487.6592. Found: 487.6596. Anal. Calcd for C₆H₂Br₂I₂:
  C, 14.78; H, 0.41. Found: C, 14.55; H, 0.43.
  1,4-Dibromo-2,3-diiodobenzene ( 5f): The first two steps followed the general procedure in ref. [11g] . Chloral hydrate (9.93 g, 60.0 mmol), 2,5-dibromoaniline (12.6 g, 50.0 mmol), hydroxylamine hydrochloride (5.21 g, 75.0 mmol), and Na₂SO₄ (60.0 g) were suspended in a mixture of H₂O (300 mL) and EtOH (300 mL). The mixture was stirred and kept at reflux for 12 h. It was then concentrated by evaporation of the ethanol and poured onto crushed ice, which caused precipitation of a white solid. After 5 h at 0 °C, the suspension was filtered, and the crystals were air dried to yield 13.5 g (84%) of crude 2,5-dibromoisonitroso-acetanilide. This amount was then cyclized by heating at 100 °C in 86% H₂SO₄ for 15 min. The resulting dark red suspension was poured onto crushed ice to yield 5.98 g (47%) of 3,6-dibromoisatine as bright orange crystals, which were subsequently subjected to basic hydrolysis in aq H₂O₂to yield 2.72 g (47%) of off-white crystals of 3,6-dibromoanthranilic acid. [11h] Finally, 3,6-dibromoanthranilic acid was converted to 1,4-dibromo-2,3-diiodobenzene by employing the aprotic diazotization procedure in ref. [11i] After column chromatography(hexanes) the product was obtained as white crystals, 2.61 g (58%), mp 97-99 °C. ¹H NMR (400 MHz, CDCl₃): δ = 7.49 (s, 2 H). ¹³C NMR (100 MHz, CDCl₃): δ = 132.8, 127.8, 117.4. MS (EI, 70 eV): m/z (%) = 488 (100) [M⁺], 361 (29), 234 (21), 153 (18), 74 (24). IR (CHCl₃): 2920, 1396, 1150, 1002, 810 cm^-1. HRMS: Calcd for C₆H₂Br₂I₂: 487.6592. Found: 487.6596. Anal. Calcd for C₆H₂Br₂I₂: C, 14.78; H, 0.41. Found: C, 14.74; H, 0.04.

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12

General Procedure for Propynylations: To a 150 mL Schlenk flask, equipped with a Teflon-coated magnetic stirring bar, were added the diiodoarene (1.67 mmol), PdCl₂(PPh₃)₂ (177 mg, 0.25 mmol), CuI (32 mg, 0.17 mmol), and Et₃N (7.50 mL). The flask was then evacuated and filled with propyne gas up to 1.5 atm (approx. 10 mmol, 3 equiv) of pressure. Depending on the system, the reaction mixture was stirred for 22-96 h, at either room or elevated temperatures (Table [1] ). The reaction mixture was then diluted with ether, washed with two portions of aq NH₄Cl, and dried over MgSO₄. Solvent was removed in vacuo and the resulting crude product purified by Kugelrohr distillation, sublimation, or chromatography.

16

General Procedure for Microwave-Assisted Propynylations: A heavy-walled Smith process vial was charged with a magnetic stirring bar, Et₃N (0.9 mL), DMF (0.1 mL), PdCl₂(PPh₃)₂ (19.6 mg, 0.028 mmol), CuI (5.4 mg, 0.028 mmol), and the dibromodiiodobenzene (0.113 mmol). The vial was sealed, evacuated, and filled with propyne through a Teflon septum up to 2.5 atm pressure. It was then irradiated in a Smith Synthesizer single-mode microwave cavity, producing continuous radiation at 2450 MHz. The resulting solution was immediately filtered through a short plug of silica gel (hexanes/ethyl acetate) to remove the catalyst and the crude product further purified by column chromatography on silica gel (hexanes).

19

General Procedure for (Me₃CO)₃WCCMe₃-Mediated Alkyne Metathesis: A 25 mL Schlenk flask was charged, under the atmosphere of nitrogen, with the respective propynylated arene (0.20-0.35 mmol), (Me₃CO)₃WCCMe₃ (20-40 mol%), and toluene (20 mL). The solution was stirred at 80 °C for 8-96 h (Table [2] ). After the reaction was complete, solvent was removed in vacuo, and the residue was subjected to flash chromatography on silica, eluting with hexane/ethyl acetate. Compound 1e: Brown crystals, showing green fluorescence, mp 292-300 °C(dec). ¹H NMR (400 MHz, CDCl₃): δ = 7.56 (s). MS (EI, 70 eV): m/z (%) = 774 (100)[M⁺], 695 (29), 614 (19). IR (CHCl₃): 2933, 2255, 1464, 1274, 1154 cm^-1. The compound decomposed upon standing for one week. Compound 2: Pale yellow crystals, showing green fluorescence, mp 310-315 °C(dec). ¹H NMR (400 MHz, CDCl₃): δ = 8.05 (br t, 2 H, J = 1.5 Hz), 7.59 (dd, 4 H, J ₁ = 3.3 Hz, J ₂ = 5.7 Hz), 7.54 (dd, 4 H, J ₁ = 1.6 Hz, J ₂ = 7.9 Hz), 7.38 (t, 2 H, J = 8.0 Hz), 7.32 (dd, 4 H, J ₁ = 3.4 Hz, J ₂ = 5.8 Hz). MS (EI, 70 eV): m/z (%) = 401(31) [M + H]⁺, 400(100) [M⁺], 199(11). HRMS: Calcd for C₃₂H₁₆: 400.1252. Found: 400.1248. UV/Vis (CH₂Cl₂): λ_max (lg ) = 265 (4.03), 272 (4.05), 278 (4.11), 280 (4.10), 317 (3.62), 341 (3.26) nm. IR (CHCl₃): 2920, 2219, 1468, 1212,
892 cm^-1. Selected spectral data for 3: ¹H NMR (400 MHz, CDCl₃): δ = 7.44 (AA′ m, 8 H), 7.34 (s, 2 H), 7.19 (BB′ m, 8 H). MS (EI, 70 eV): m/z (%) = 524 (10) [M + 2H]⁺, 523 (42) [M + H]⁺, 522 (100) [M⁺], 261 (25) [M²⁺]. HRMS: Calcd for C₄₂H₁₈: 522.1408. Found: 522.1428.

21

The spectral data are in good agreement with those in ref. [17a]

24

Details of the crystal structure determination (deposition number CCDC 192630) may be obtained free of charge on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [Fax: [phone]; E-mail: [e-mail]].