[Ir(cod)Cl]₂/FDPPE-Catalyzed Chemo- and Regioselective Cyclotrimerization of Two Different Terminal Alkynes To Give 1,3,5-Trisubstituted Benzenes

Abstract

[Ir(cod)Cl]₂ in combination with 1,2-bis(dipentafluorophenylphosphino)ethane catalyzes chemo- and regioselective cyclotrimerization of two different alkynes. The reaction of methyl propiolate with 1-hexyne gave methyl 3,5-di(n-butyl)benzoate as a single product in 88% yield.

iridium - cyclotrimerization - regioselectivity - alkynes - catalysis

References and Notes

1

Present address: Department of Applied Chemistry, Tokai University, Hiratsuka, 259-1292, Japan.

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6

Typical Experimental Procedure for the Reaction of Methyl Propiolate (1a) with 1-Hexyne (2a) Catalyzed by [Ir(cod)Cl] ₂ /FDPPE and Spectral Data of Methyl 3,5-Di( n -butyl)benzoate (3aa) Into a two-necked flask with a stirring bar were placed [IR (cod)Cl]₂ (13.6 mg, 0.02 mmol) and FDPPE (30.9 mg, 0.040 mmol). The flask was evacuated and filled with Ar. Then, anhydrous THF (5.0 mL) was added to the flask. To the stirred solution was added 1-hexyne (2a, 243 mg, 3.0 mmol). Methyl propiolate (1a, 83.3 mg, 1.0 mmol) was then added dropwise to the reaction mixture. The reactor was immersed in an oil bath, which was kept at 75 °C. The reaction mixture was heated under reflux for 1 h. The progress of the reaction was monitored by GLC. After the reaction was completed, the solvent was concentrated in vacuo. Column chromatography of the residue gave 3aa as a colorless oil (n-hexane-EtOAc = 99:1, 219 mg, yield 88%). ¹H NMR (500 MHz, CDCl₃): δ = 0.93 (t, J = 7.3 Hz, 6 H), 1.35 (sext, J = 7.3 Hz, 4 H), 1.58-1.64 (m, 4 H), 2.62 (t, J = 7.8 Hz, 4 H), 3.90 (s, 3 H), 7.18 (s, 1 H), 7.68 (d, J = 1.8 Hz, 2 H). ¹³C NMR (125 MHz, CDCl₃): δ = 13.9 (2 C), 22.3 (2 C), 33.6 (2 C), 35.4 (2 C), 51.9, 126.9 (2 C), 130.1, 133.4, 143.1 (2 C), 167.6. Anal. Calcd for C₁₆H₂₄O₂: C, 77.38; H, 9.74; O, 12.88. Found: C, 77.49; H, 9.74.

7

All new compounds were fully characterized.

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10

Typical Procedure for the Reaction of 3aa To Give 3,5-Di( n -butyl)benzaldehyde (4aa) and Spectral Data of 4aa
A flask was charged with LiAlH₄ (57 mg, 1.5 mmol). The flask was evacuated and filled with argon. To the flask was added Et₂O (3 mL). An ether solution (3.0 mL) of benzoate 3aa (248 mg, 1 mmol) was added dropwise to the reaction mixture. The mixture was stirred at r.t. for 4 h. The progress of the reaction was monitored by TLC. After the reaction was complete, the mixture was poured into 2 M HCl, and the aqueous layer was extracted with Et₂O. The combined organic layers were washed with a solution of sat. aq NaHCO₃ and dried with Mg₂SO₄. The solvent was evaporated in vacuo. Another flask was charged with MnO₂ (869 mg, 10 mmol). The flask was evacuated and filled with argon. Then, CH₂Cl₂ (2 mL) was added to the flask. The CH₂Cl₂ solution (3 mL) of the residue was then added to the stirred reaction mixture. The reaction mixture was stirred at r.t. for 30 h. The progress of the reaction was monitored by GLC and TLC. After the reaction was complete, the mixture was filtered through a Celite pad. The solution was evaporated in vacuo. Column chromatography of the residue gave 4aa as a colorless oil (n-hexane-EtOAc = 99:1, 192 mg, yield 88%). ¹H NMR (500 MHz, CDCl₃): δ = 0.94 (t, J = 7.3 Hz, 6 H), 1.36 (sext, J = 7.3 Hz, 4 H), 1.59-1.65 (m, 4 H), 2.66 (t, J = 7.8 Hz, 4 H), 7.26 (s, 1 H), 7.51 (d, J = 1.4 Hz, 2 H), 9.97 (s, 1 H). ¹³C NMR (125 MHz, CDCl₃): δ = 13.9 (2 C), 22.3 (2 C), 33.4 (2 C), 35.3 (2 C), 127.1 (2 C), 135.0, 136.6, 143.8 (2 C), 192.8. HRMS: m/z calcd for C₁₅H₂₂O [M⁺]: 218.1671; found: 218.1651.

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