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

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.

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

References and Notes

Reviews:

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See the reviews:

11a Denmark SE. Nazarov and Related Cationic Cyclizations, In Comprehensive Organic Synthesis   Vol. 5:  Trost BM. Fleming I. Paquette LA. Pergamon; Oxford, UK: 1991.  p.751-784  

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13

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): ν_max = 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): ν_max = 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.