One-Pot, Three-Component Synthesis of 4-Aryl-5,6-dihydropyran via Prins-Friedel-Crafts Reaction

Abstract

An efficient method for the synthesis of 4-aryldihydropyrans has been developed from the reaction of aldehydes or epoxides with homopropargylic alcohols in the presence of arenes promoted by boron trifluoride etherate

Lewis acid - multicomponent - Prins cyclization - Friedel-Crafts reaction - dihydropyran

References and Notes

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Synthesis of 2,4-Diphenyl-5,6-dihydro-2 H -pyran (1b)
To a mixture of benzaldehyde (0.10 mL, 1.0 mmol) and homopropagyl alcohol (140 mg, 2.0 mmol) in dry benzene (2.0 mL) was added freshly distilled BF₃˙OEt₂ (0.15 mL, 1.2 mmol) under nitrogen atmosphere. The reaction mixture was stirred at 40 ˚C for 8 h. The progress of the reaction was monitored by TLC with EtOAc and hexane as eluents. After completion of the reaction, the reaction mixture was treated with aq NaHCO₃, the mixture was extracted with Et₂O, and the combined organic extracts washed with brine and water. The organic layer was dried (Na₂SO₄) and evaporated to leave the crude product, which was purified by short column chromatography over silica gel to give 2,4-diphenyl-5,6-dihydro-2H-pyran 1b (106 mg, 45% yield) as a liquid. ^¹H NMR (400 MHz, CDCl₃): δ = 2.45-2.52 (m, 1 H), 2.70-2.80 (m, 1 H), 3.92 (ddd, J = 11.6, 8.8, 4.0 Hz, 1 H), 4.18 (ddd, J = 11.6, 5.2, 3.6 Hz, 1 H), 5.30 (d, J = 2.4 Hz, 1 H), 6.22 (d, J = 1.2 Hz, 1 H), 7.23-7.45 (m, 10 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 27.3, 63.6, 72.4, 124.3, 124.4, 125.1, 127.9, 128.6 (2 C), 129.6, 133.4, 135.5, 136.9, 139.9, 148.5. IR: 3029, 2923, 2854, 1600, 1493, 1453, 1273, 1119, 1075, 1029, 886, 749, 698 cm^-¹. HRMS (APCI): m/z calcd for C₁₇H₁₆O [M + H]⁺: 237.1279; found: 237.1258.
6-Isopropyl-4-phenyl-5,6-dihydro-2 H -pyran (22)
To a mixture of 1,2-epoxy-2-methylpropane (0.09 mL, 1.0 mmol) and homopropagyl alcohol (140 mg, 2.0 mmol) in dry benzene (3.0 mL) was added freshly distilled BF₃˙OEt₂ (0.15 mL, 1.2 mmol) under nitrogen atmosphere. The reaction mixture was stirred at r.t. for 5 h. The progress of the reaction was monitored by TLC with EtOAc and hexane as eluents. After completion of reaction, the reaction mixture was treated with aq NaHCO₃, and the product was extracted with Et₂O, and then the combined organic extracts washed with brine and H₂O. The organic layer was dried (Na₂SO₄) and evaporated to leave the crude product, which was purified by short column chromatography over silica gel to give 6-isopropyl-4-phenyl-5,6-dihydro-2H-pyran 25 (90 mg, 45% yield) as a liquid. ^¹H NMR (400 MHz, CDCl₃): δ = 0.99 (t, J = 6.8 Hz, 6 H), 1.82-1.93 (m, 1 H), 2.27-2.40 (m, 1 H), 2.60-2.71 (m, 1 H), 3.73 (dt, J = 10.4, 3.2 Hz, 1 H), 4.00-4.06 (m, 1 H), 4.16 (ddd, J = 10.8, 5.6, 1.6 Hz, 1 H), 6.10 (m, 1 H), 7.24-7.28 (m, 1 H), 7.30-7.36 (m, 2 H), 7.38-7.42 (m, 2 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 18.1, 18.6, 27.7, 33.3, 64.2, 79.4, 125.0 (2C), 127.5, 127.7, 135.6, 140.8. IR: 2960, 2853, 1645, 1494, 1363, 1115, 1089, 880, 751, 699 cm^-¹. HRMS (APCI): m/z calcd for C₁₄H₁₈O [M + H]⁺: 203.1436; found: 203.1431.

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The product 26 was sensitive to silica gel. While purifying the compound by column chromatography, it was decomposed. Therefore, the silica gel of the column chromatography was impregnated with 3% Et₃N in hexane during the purification

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<A NAME="RD01910ST-12B">12b</A> Li J. Li C.-J. Tetrahedron Lett.  2001,  42:  793