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Synlett 2008(3): 458-462  
DOI: 10.1055/s-2008-1032065
LETTER
© Georg Thieme Verlag Stuttgart · New York

Toward the Synthesis of Caraphenol C: Substituent Effect on the Nazarov ­Cyclization of 2-Arylchalcones

Jun Zhua, Chen Zhonga, Hong-Fu Lua, Guang-Yu Lib, Xun Sun*a
a Department of Chemistry of Natural Drugs, School of Pharmacy, Fudan University, 138 Yixueyuan Road, Shanghai 200032, P. R. of China
Fax: +86(21)54237607; e-Mail: sunxunf@shmu.edu.cn;
b Laboratory of Analytical Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Road, Shanghai 200032, P. R. of China
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Publication History

Received 24 September 2007
Publication Date:
23 January 2008 (online)

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Abstract

A mild and versatile synthesis of cis-2,3-diarylindanones using a Nazarov cyclization strategy was reported. The substituent effect on the stereochemistry of the cyclization was discussed.

Key words

caraphenol C - chalcone - 2,3-diarylindanone - Lewis acid - Nazarov cyclization

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General Procedure for the Synthesis of 2-(3,5-dimethoxyphenyl)-4,6-dimethoxy-3-(4-methoxyphenyl)-2,3-dihydroinden-1-one
Compound cis -8g
To a solution of α-substituted chalcones 7g (2.78 g, 6.40 mmol) in CH2Cl2 (70 mL) was added dropwise BF3·OEt2 (8.11 mL, 64 mmol) via syringe. After the reaction mixture was stirred at r.t. for 7 min under a nitrogen atmosphere, the reaction was quenched by the addition of H2O (60 mL). The resulting mixture was extracted with CH2Cl2 (3 × 60 mL). The combined organic phase was washed with brine and dried over anhyd Na2SO4. After removal of solvent, the resulting yellow residue was washed by the solution of EtOAc in PE (1-2%). The pure product cis-8g (2.6 g, 94%) was obtained after trituration as a white solid; mp 146-148 °C. IR (KBr): νmax = 2837, 1705, 1608, 1596, 1512, 1150 cm-1. 1H NMR (300 MHz, CDCl3): δ = 3.56 (s, 6 H), 3.66 (s, 3 H), 3.71 (s, 3 H), 3.91 (s, 3 H), 4.27 (d, 1 H, J = 7.8 Hz), 4.92 (d, 1 H, J = 7.8 Hz), 5.90-7.26 (m, 9 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 47.3, 55.1, 55.67, 55.7, 55.8, 61.9, 96.1, 99.3, 106.2, 108.4, 113.0, 129.3, 132.4, 136.7, 138.3, 139.0, 157.6, 158.0, 160.0, 161.7, 205.4 ppm. MS (EI): m/z (%) = 434 (100) [M+] , 326 (25.54) [M+ - PhOCH3].
Compound trans -8g To a solution of α-substituted chalcones 7g (3.21 g, 7.40 mmol) in CH2Cl2 (100 mL) was added dropwise BF3·OEt2 (9.38 mL, 74 mmol). After the reaction solution was stirred for 40 h at r.t. under a nitrogen atmosphere, the reaction mixture was quenched by the addition of H2O (80 mL). The resulting mixture was extracted with CH2Cl2 (3 × 70 mL). The combined organic phase was washed with brine and dried over anhyd Na2SO4. After removal of solvent, the residue was subjected to purification on silica gel by flash column chromatography (PE-EtOAc, 5:1) to afford the pure product trans-8g (2.68 g, 85%) as a white solid; mp 168-169 °C. IR (KBr): νmax = 2937, 2840, 1711, 1610, 1514, 1202, 1156 cm-1. 1H NMR (300 MHz, CDCl3): δ = 3.60 (d, 1 H, J = 3.0 Hz, 3-H), 3.66 (s, 3 H, OCH3), 3.73 (s, 6 H, 2 × OCH3), 3.78 (s, 3 H, OCH3), 3.87 (s, 3 H, OCH3), 4.51 (d, 1 H, J = 3.0Hz, 2-H), 6.23-6.95 (m, 9 H, ArH) ppm. 13C NMR (75 MHz, CDCl3): δ = 50.8, 55.2, 55.3, 55.6, 55.8, 65.3, 96.4, 98.9, 106.0, 106.6, 113.8, 127.9, 128.1, 135.4, 138.5, 141.5, 157.7, 158.1, 160.9, 161.9, 205.5. MS (EI): m/z (%) = 434 (100) [M+] , 326 (22.59) [M+ - CH3OPhCH]. HRMS (EI): m/z calcd for C26H26O6: 434.1721; found: 434.1713.