Ruthenium-Catalyzed Rearrangement of cis-1-Ethynyl-2-vinyloxiranes to Substituted Phenols

Abstract

Catalytic cyclization of cis-1-ethynyl-2-vinyloxiranes was implemented with TpRuPPh₃(CH₃CN)₂PF₆ catalyst (10 mol%), to give 2,6-disubstituted phenols in reasonable yields. Under similar conditions, 1,1,2,2-tetrasubstituted oxirane gave the 2,3,6-trisubstituted phenol with skeleton reorganization. On the basis of ²H- and ¹³C-labeling results, we propose that the reaction mechanism involves electrocyclization of ruthenium-vinylidene intermediate with cleavage of the carbon-oxygen bond of the epoxide.

cis-1-ethynyl-2-vinyloxiranes - 2,6-disubstituted phenols - TpRuPPh₃(CH₃CN)₂PF₆ - ruthenium-vinylidine intermediate - endo-dig cyclization - 1,2-hydrogen shift

References and Notes

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<A NAME="RW30505ST-13">13</A>

Procedure for the Synthesis of Epoxide 5.
To a CH₂Cl₂ solution (60 mL) of species 1 (2.87 g, 13.64 mmol) was added MCPBA and the mixture was stirred at 28 °C for 4 h. The resulting suspension was quenched with H₂O. The aqueous layer was extracted with CH₂Cl₂ twice. The combined organic layer was washed with H₂O, dried over MgSO₄ and the solvent was removed in vacuo. The resulting mass was eluted through a Et₃N-pretreated silica column (EtOAc-hexane, 1:20) to get the epoxide 2 as a colorless oil (1.86 g, 8.22 mmol, 60%).
To a solution of oxalyl chloride (1.26 mL, 14.57 mmol) in CH₂Cl₂ (40 mL) maintained at -60 °C was added DMSO (2.09 mL, 29.14 mmol) with stirring. After 15 min a solution of 2 (1.65g, 7.30 mmol) in CH₂Cl₂ (5 mL) was added and the stirring continued for 1 h at -60 °C. Then, Et₃N (8.83 mL, 63.35 mmol) was added and the reaction mixture was allowed to attain 28 °C over 2 h. Afterwards, H₂O was added and the organic layer was separated. It was washed with brine, dried over MgSO₄ and concentrated. The crude mass was eluted through Et₃N-pretreated silica column (EtOAc-hexanes, 1:20) to get the epoxy ketone 3 as a colorless oil (1.55 g, 6.91 mmol, 92%).
To a solution of methyltriphenylphosphonium bromide (3.66 g, 10.24 mmol) in THF (45 mL) at -20 °C was added n-BuLi (3.77 mL, 9.42 mmol), and the mixture was stirred at that temperature for 1 h and then cooled to -78 °C. To the resulting solution was added a solution of 3 (1.15 g, 5.12 mmol) in THF (5 mL) over 10 min and the resulting reaction mixture was allowed to warm to -30 °C over 2 h. The reaction was quenched with sat. aq NH₄Cl and concentrated in vacuo. The organic mass was extracted into Et₂O. The ether layer was washed with brine, dried over MgSO₄ and concentrated in vacuo. The residue was purified by column chromatography over a Et₃N-pretreated silica column (hexane) to get the olefination product 4 as a colorless oil (0.80 g, 3.60 mmol, 70%).
To a solution of this silyl compound 4 in THF (5 mL) was added Bu₄NF (1 M, 3.6 mL, 3.6 mmol) under ice conditions and allowed the resulting solution to warm to 26 °C over
4 h. Then, H₂O (5 mL) was added and the solution was concentrated, extracted with Et₂O. The ether layer was dried over MgSO₄ and concentrated in vacuo. Elution of the crude enyne through a Et₃N-pretreated silica column (hexane) gave 5 (0.50 g, 3.33 mmol, 93%).

<A NAME="RW30505ST-14">14</A>

Typical Procedure for Cyclization of 2-Ethynyl-3-isopropenyl-2-propyl Oxirane ( 5) to 2-Methyl-6-propylphenol ( 6). A long tube containing TpRu(PPh₃)(CH₃CN)₂PF₆ (50.7 mg, 0.067 mmol) was dried in vacuo for 2 h. It was then charged with epoxide 5 (100 mg, 0.67 mmol) and freshly distilled toluene (0.6 mL). The mixture was heated at 100 °C for 16 h and then cooled to r.t. Concentration of the solution followed by elution through a silica column (hexane-Et₂O = 5:1) afforded the phenol 6 (57 mg, 0.38 mmol, 57%) as a pale-yellow oil.
Spectral Data for 2-Ethynyl-3-(prop-1-en-2-yl)-2-propyloxirane ( 5).
IR (nujol): 3300 (m), 2235 (w), 1645 (w), 1210 (m) cm^-1. ¹H NMR (600 MHz, CDCl₃): δ = 5.05 (dd, J = 2.98, 1.64 Hz, 2 H), 3.24 (s, 1 H), 2.29 (s, 1 H), 1.80 (s, 3 H), 1.61-1.58 (m, 1 H), 1.56-1.55 (m, 3 H), 0.96 (t, J = 7.0 Hz, 3 H). ¹³C NMR (150 MHz, CDCl₃): δ = 138.6, 113.1, 80.1, 73.2, 65.7, 57.1, 38.9, 19.1, 18.8, 13.7. MS (75 eV): m/z = 150 [M⁺]. HRMS: m/z calcd for C₁₀H₁₄O: 150.1045; found: 150.1049.
Spectral Data for 2-Methyl-6-propylphenol ( 6).
IR (nujol): 3416 (s), 1620 (s), 1585 (m), 1230 (s) cm^-1. ¹H NMR (600 MHz, CDCl₃): δ = 6.95 (d, J = 6.8 Hz, 2 H), 6.76 (t, J = 7.5 Hz, 1 H), 4.61 (s, 1 H), 2.55 (t, J = 7.6 Hz, 2 H), 2.23 (s, 3 H), 1.64-1.61 (m, 2 H), 0.96 (t, J = 7.4 Hz, 3 H). ¹³C NMR (150 MHz, CDCl₃): δ = 151.8, 128.5, 127.9, 127.6, 123.0, 120.2, 32.1, 22.9, 15.9, 14.1. MS (75 eV): m/z = 150 [M⁺]. HRMS: m/z calcd for C₁₀H₁₄O: 150.1045; found: 150.1043.

<A NAME="RW30505ST-15">15</A>

In a separate experiment, epoxide 12 (0.6 M) was heated alone in toluene (100 °C, 12 h), and we isolated the phenol 18 and aldehyde 21 in 4% and 10%, respectively, whereas the starting epoxide 12 was recovered in 51% (Scheme [10] ).