Download PDF
Synlett 2006(6): 909-915  
DOI: 10.1055/s-2006-939048
LETTER
© Georg Thieme Verlag Stuttgart · New York

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

Antonio Arcadia, Sandro Cacchi*b, Giancarlo Fabrizib, Fabio Marinelli*a, Mirella Verdecchiaa
a Dipartimento di Chimica, Ing. Chimica e Materiali, via Vetoio, 67100 L’Aquila, Italy
b Dipartimento di Studi di Chimica e Tecnologia delle Sostanze Biologicamente Attive, Università degli Studi ‘La Sapienza’, P. le A. Moro 5, 00185 Rome, Italy
e-Mail: sandro.cacchi@uniroma1.it; e-Mail: fmarinel@univaq.it;
Further Information

Publication History

Received 27 October 2005
Publication Date:
14 March 2006 (online)

    Permissions and Reprints All articles of this category

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.

Key words

chromenes - palladium catalysis - cyclization - hydro­vinylation - hydroarylation

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].

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].