4-Aryl- and 4-Vinyl-2,2-Dialkyl-3-chromenes from Tertiary 3-(o-Bromophenyl)propynols via a Palladium-Catalyzed Hydroarylation/Hydrovinylation-Cyclization Sequence

Abstract

4-Aryl- and 4-vinyl-2,2-dialkyl-3-chromenes were prepared from tertiary 3-(o-bromophenyl)propynols and aryl iodides or vinyl triflates through a one-pot process, which involves the addition of t-BuONa, dppf and, where appropriate, fresh Pd(OAc)₂ to the crude mixture resulting from the hydroarylation or hydrovinylation step [Pd(OAc)₂, Et₃N, HCOOH, Bu₄NCl, toluene]. In general, 4-aryl- and 4-vinyl-2,2-dialkyl-3-chromenes are obtained with high regioselectivity and overall yields range from satisfactory to high. Vinyl triflates tend to give higher yields than aryl iodides.

chromenes - palladium catalysis - cyclization - hydro­vinylation - hydroarylation

References and Notes

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15

Hydroarylation/Hydrovinylation-Cyclization of 1; Procedure A To a stirred solution of 1a (0.160 g, 0.67 mmol) and 2b (0.395 g, 1.61 mmol) in THF (5 mL) were added Bu₃N (0.572 mL, 2.41 mmol), BuN₄Cl (0.198 g, 0.67 mmol), and Pd(OAc)₂ (0.008 g, 0.035 mmol). The solution was stirred under nitrogen for 3 min. Then, HCOOH (0.066 mL, 1.74 mmol) was added. The reaction mixture was stirred at 60 °C under nitrogen for 24 h, then cooled, and extracted with 0.1 M HCl (100 mL) and Et₂O (3 × 50 mL). The combined organic layers were washed with 5% NaHCO₃ (30 mL), dried over Na₂SO₄, and concentrated under reduced pressure. The residue was dissolved in toluene (5 mL), Pd(OAc)₂ (0.008 g, 0.035 mmol), dppf (0.019 g, 0.035 mmol), and t-BuONa (0.129 g, 1.34 mmol) were added and the reaction mixture was stirred at 110 °C under nitrogen for 16 h. After cooling, the mixture was extracted with 0.5 M NH₄Cl (100 mL) and EtOAc (3 × 50 mL). The combined organic layers were dried over Na₂SO₄ and concentrated under reduced pressure. The residue was purified by chromatography (silica gel; n-hexane-EtOAc, 98:2) to give 4b (0.117 g, 61%); mp 113-115 °C. IR (KBr): 1690, 1610, 1270 cm^-1. ¹H NMR (CDCl₃): δ = 7.99 (d, J = 8.4 Hz, 2 H), 7.45 (d, J = 8.4 Hz, 2 H), 7.21-7.13 (m, 1 H), 6.97-6.78 (m, 3 H), 5.67 (s, 1 H), 2.63 (s, 3 H), 1.50 (s, 6 H). ¹³C NMR (CDCl₃): δ = 197.7, 153.3, 143.3, 136.3, 134.1, 130.0, 129.5, 128.9, 128.4, 128.3, 125.3, 120.7, 117.1, 75.7, 27.5, 26.7. EI-MS: m/z (%) = 263 (100) [M⁺ - CH₃].

16

One-Pot Hydroarylation/Hydrovinylation-Cyclization of 1; Procedure B To a stirred solution of 1a (0.143 g, 0.60 mmol) and 2d (0.153 g, 0.50 mmol) in DMF (2 mL) were added Pd(OAc)₂ (0.006 g, 0.026 mmol) and HCOOK (0.084 g, 1.00 mmol). The reaction mixture was stirred at 40 °C under nitrogen for 17 h, then cooled, and extracted with 5% NaHCO₃ (100 mL) and Et₂O (3 × 50 mL). The combined organic layers were dried over Na₂SO₄ and concentrated under reduced pressure. The residue was dissolved in toluene (5 mL), Pd(OAc)₂ (0.006 g, 0.026 mmol), dppf (0.014 g, 0.026 mmol), and
t-BuONa (0.096 g, 1.00 mmol) were added and the reaction mixture was stirred at 110 °C under nitrogen for 5 h. After cooling, the mixture was extracted with 0.5 M NH₄Cl (100 mL) and EtOAc (3 × 50 mL). The combined organic layers were dried over Na₂SO₄ and concentrated under reduced pressure. The residue was purified by chromatography (silica gel; n-hexane-EtOAc, 99:1) to give 4d (0.063 g, 40%); mp 55-57 °C. IR (KBr): 1610, 1480, 1450, 1260 cm^-1. ¹H NMR (CDCl₃): δ = 7.32-7.07 (m, 7 H), 6.90-6.81 (m, 2 H), 5.83 (br s, 1 H), 5.47 (s, 1 H), 2.95-2.80 (m, 1 H), 2.38-1.80 (m, 6 H), 1.42 (s, 3 H), 1.40 (s, 3 H). ¹³C NMR (CDCl₃): δ = 153.3, 146.8, 136.3, 135.5, 128.8, 128.4, 126.8, 126.5, 126.3, 126.1, 125.2, 121.9, 120.5, 116.9, 75.5, 39.8, 33.6, 30.0, 29.2, 27.6, 27.5. EI-MS: m/z (%) = 316 (2) [M⁺], 301 (100) [M⁺ - CH₃].

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22

One-Pot Synthesis of Chromenes without Work-up after Hydroarylation/Hydrovinylation
To a stirred solution of 1a (0.161 g, 0.67 mmol) and 2j (0.145 g, 0.56 mmol) in toluene (3 mL) were added Et₃N (0.234 mL, 1.68 mmol), BuN₄Cl (0.166 g, 0.56 mmol), and Pd(OAc)₂ (0.003 g, 0.014 mmol). The solution was stirred under nitrogen for 5 min and then HCOOH (0.042 mL, 1.12 mmol) was added. The reaction mixture was stirred at 50 °C under nitrogen for 7 h, then Pd(OAc)₂ (0.003 g, 0.014 mmol), dppf (0.016 g, 0.029 mmol), and NaOt-Bu (0.216 g, 2.25 mmol) were added, the temperature was raised to 110 °C and the reaction mixture was stirred under nitrogen for 16 h. After cooling, the mixture was extracted with 0.5 M NH₄Cl (100 mL) and EtOAc (3 × 50 mL). The combined organic layers were dried over Na₂SO₄ and concentrated under reduced pressure. The residue was purified by chromatography (silica gel; n-hexane-EtOAc, 99:1) to give 4j (0.124 g, 82%) as an oil. IR: 1630, 1500, 1470, 1280 cm^-1. ¹H NMR (CDCl₃): δ = 7.08-7.01 (m, 2 H), 6.85-6.78 (m, 2 H), 5.68 (t, J = 8.2 Hz, 1 H), 5.39 (s, 1 H), 2.34-2.21 (m, 4 H), 1.60-1.44 (m, 8 H), 1.41 (s, 6 H). ¹³C NMR (CDCl₃): δ = 153.3, 139.0, 136.6, 129.5, 128.7, 127.0, 126.9, 125.4, 120.4, 116.7, 75.6, 29.9, 28.6, 28.4, 27.8, 26.6, 26.3. EI-MS: m/z (%) = 268 (7) [M⁺], 253 (100) [M⁺ - CH₃].