Stereoselective, One-Pot, Three-Component Synthesis of 4-Aryltetrahydropyrans from Epoxides via Prins Cyclization Reaction

Abstract

A three-component, one-pot synthesis of 4-aryltetra­hydropyrans from epoxides and homoallylic alcohols in arenes via Prins-Friedel-Crafts reaction, mediated by boron trifluoride etherate, has been developed. The reaction is diastereoselective and gives only all-cis diastereomers in moderate to good yields.

Key words

stereoselective - Prins cyclization - epoxide - homoallylic alcohol - boron trifluoride etherate - tetrahydropyran

References and Notes

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6

Balaban, T. S.; Buettner, A.; Roussel, C.; Vanthuyne, N.; Schieberle, P. State-of-the-Art in Flavour Chemistry and Biology, In Proceedings of the 7th Wartburg Symposium on Flavour Chemistry and Biology, Eisenach, Germany, 2004; abstract 31

10

2-Benzyl-4-phenyltetrahydropyran (1) To a mixture of 2-phenyloxirane (60 mg, 0.5 mmol) and but-3-en-1-ol (44 mg, 0.6 mmol) in benzene (3 mL) was added freshly distilled BF₃×OEt₂ (71 mg, 0.5 mmol). The reaction mixture was stirred at r.t. for the specified time. The progress of the reaction was monitored by TLC. After completion of the reaction, the reaction mixture was treated with aq NaHCO₃, and the product was extracted with EtOAc, and then the organic layer was washed with brine. The organic layer was dried over (Na₂SO₄) and evaporated to leave the crude product which was purified by column chromatography over silica gel to give the 2-benzyl-4-phenyltetrahydropyran (75 mg, 60%) as a pale yellow liquid. ^¹H NMR (400 MHz, CDCl₃): δ = 1.47 (ddd, J = 12.4, 12.4, 11.6 Hz, 1 H), 1.68-1.85 (m, 3 H), 2.68-2.76 (m, 2 H), 2.97 (dd, J = 13.6, 6.4 Hz, 1 H), 3.57 (dddd, J = 11.6, 11.6, 3.2, 2.8 Hz, 1 H), 3.64 (dddd, J = 10.8, 4.8, 2.0, 1.6 Hz, 1 H), 4.12 (dddd, J = 11.2, 7.2, 6.0, 3.6 Hz, 1 H), 7.18-7.23 (m, 5 H), 7.25-7.32 (m, 5 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 33.6, 39.2, 41.9, 43.3, 68.5, 78.9, 126.4, 126.5, 127.0, 128.5, 128.7, 129.6, 138.6, 145.9. IR (KBr, neat): 2934, 2844, 1637, 1379, 1125, 1085, 1026, 750, 698 cm^-¹. Anal. Calcd for C₁₈H₂₀O: C, 85.67; H, 7.99. Found: C, 85.52; H, 8.05.
2-Benzyltetrahydro-4- o / p -tolyl-2 H -pyran (15, o / p  = 3:2) To a mixture of phenyloxirane (60 mg, 0.5 mmol), but-3-en-1-ol (44 mg, 0.6 mmol), and toluene (230 mg, 2.5mmol) in CH₂Cl₂ (2 mL) was added freshly distilled BF₃×OEt₂ (71 mg, 0.5 mmol). The reaction mixture was stirred at r.t. for the specified time. The progress of the reaction was monitored by TLC. After completion of the reaction, the reaction mixture was treated with aq NaHCO₃, and the product was extracted with EtOAc, and then the organic layer was washed with brine. The organic layer was dried over (Na₂SO₄) and evaporated to leave the crude product which was purified by column chromatography over silica gel to give the 2-benzyltetrahydro-4-o/p-tolyl-2H-pyran in the ratio of 3:2 (95 mg, 72%) as a colorless liquid. ^¹H NMR (400 MHz, CDCl₃): δ = 1.45 (ddd, J = 12.4, 12.4, 11.2 Hz, 1 H), 1.49 (ddd, J = 12.4, 12.4, 11.6 Hz, 1 H), 1.64-1.82 (m, 3 H), 2.29 (s, 1.8 H), 2.31 (s, 1.2 H), 2.64-2.74 (m, 1 H), 2.91-3.00 (m, 1 H), 3.51-3.70 (m, 2 H), 4.08-4.15 (m, 1 H), 6.97-7.02 (m, 1 H), 7.06-7.14 (m, 3 H), 7.17-7.29 (m, 5 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 19.5, 21.1, 33.0, 33.7, 37.5, 38.3, 39.2, 39.3, 41.9, 43.2, 68.5, 68.7, 78.9, 79.1, 123.9, 125.7, 126.1, 126.3, 126.5, 126.8, 127.2, 127.7, 129.3, 129.5 (2 C), 130.5, 135.2, 135.9, 138.6, 143.0, 143.7, 145.9. IR (KBr, neat): 2937, 2842, 1634, 1454, 1378, 1125, 1085, 749, 700 cm^-¹. Anal. Calcd for C₁₉H₂₂O: C, 85.67; H, 8.32. Found: C, 85.79; H, 8.25.