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Synlett 2007(9): 1357-1364  
DOI: 10.1055/s-2007-980353
LETTER
© Georg Thieme Verlag Stuttgart · New York

Three-Component Barbier Allylation, Friedel-Crafts Alkylation and Intramolecular Hydroalkoxylation in an Ionic Liquid for the Direct Synthesis of 4-Arylchromans

Xian-Liang Zhao, Li Liu*, Yong-Jun Chen, Dong Wang*
Beijing National Laboratory for Molecular Sciences (BNLMS), Laboratory for Chemical Biology, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100080, P. R. of China
Fax: +86(10)62554449; e-Mail: lliu@iccas.ac.cn, dwang210@iccas.ac.cn;
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Publication History

Received 26 December 2006
Publication Date:
23 May 2007 (online)

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Abstract

4-Arylchromans can be synthesized directly using a one-pot Barbier allylation, Friedel-Crafts alkylation and intramolecular hydroalkoxylation of aromatic aldehydes, allylbromides and ­phenols in an ionic liquid (BPyX-SnCl2·2H2O). The intramolecular hydroalkoxylation of 4-aryl-4-(2-hydroxylphenyl)but-1-enes can be promoted using the Lewis acid ZnCl2 in an ionic liquid.

Key words

Barbier - Friedel-Crafts - hydroalkoxylation - one-pot process - 4-arylchroman - ionic liquid

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2-Methyl-4-(4′-hydroxylphenyl)chroman (8a): A mixture of salicylaldehyde 6a (61 mg, 0.5 mmol), allyl bromide (2a) (120 mg, 1 mmol) and phenol 3a (69 mg, 0.75 mmol) in ionic liquid (10a) derived from BPyCl-SnCl2·2H2O was stirred at ambient temperature for 10 h. ZnCl2 (102 mg, 0.75 mmol) was added, followed by stirring at 70 °C for 5 h. The reaction mixture was extracted with Et2O. The combined Et2O extracts were washed with aqueous HCl (2 M), and then dried over Na2SO4. The solvent was removed under vacuum and the crude product was purified by flash column chromatography on silica gel (EtOAc-PE, 1:30) to afford 8a as a colorless oil (84 mg, 70%); FTIR (film): 3394, 2971, 1649, 1612, 1581, 1514, 1483, 1455, 1232 cm-1; 1H NMR (300 MHz, CDCl3): δ = 7.10-7.30 (m, 6 H), 6.72-7.07 (m, 2 H), 4.12-4.34 (m, 2 H), 1.91-1.26 (m, 2 H), 1.38, 1.48 (2 × d, J = 6.9, 6.2 Hz, 3 H); 13C NMR (75 MHz, CDCl3): δ = 154.9, 153.9 (153.6)*, 138.6, 136.7, 130.5, 129.4, 129.3, 127.2 (127.6), 125.7, 120.0, 116.2 (116.5), 114.8 (115.2), 67.2 (72.2), 41.8 (38.8), 39.7 (37.5), 20.7 (21.1); (* data in parentheses represents diastereomeric peaks); HRMS (EI): m/z calcd for C16H16O2: 240.1150; found: 240.1149.

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2,2-Dimethyl-4-(4′-hydroxylphenyl)chroman (9a): A mixture of salicylaldehyde 6a (61 mg, 0.5 mmol), 2-methyl-allyl chloride (2b) (82 mg, 1.0 mmol) and phenol 3e (69 mg, 0.75 mmol) in ionic liquid (10b) derived from BPyI-SnCl2·2H2O was stirred at 40 °C for 24 h. The reaction mixture was extracted with Et2O. The combined Et2O phase was washed with aqueous HCl (2 M), then dried over Na2SO4. The solvent was removed under vacuum and the crude product was purified by flash column chromatography on silica gel (EtOAc-PE, 1:30) to afford 9a as a colorless oil (83 mg, 66%); FTIR (film): 3394, 2925, 1612, 1571, 1514, 1486, 1449, 1368, 1253, 1124 cm-1; 1H NMR (300 MHz CDCl3): δ = 7.01-7.16 (m, 3 H), 6.69-6.88 (m, 5 H), 5.63 (br s, 1 H), 4.01 (dd, J = 7.2, 4.8 Hz, 1 H), 2.08-2.33 (m, 2 H), 1.43 (s, 3 H), 1.36 (s, 3 H); 13C NMR (75 MHz, CDCl3): δ = 154.6, 154.2, 137.1, 129.9, 127.7, 125.0, 119.9, 117.2, 115.5, 74.8, 43.6, 39.1, 30.0, 24.3; HRMS (EI): m/z calcd for C17H18O2: 254.1307; found: 254.1308.