A Diels–Alder Approach toward the Scaffolds of Polycyclic Sesquiterpenoids with 2-Pyrone

Abstract

Functionalized 2-pyrone was synthesized from a known compound through an eight-step reaction sequence. Diels–Alder cycloadditions of this 2-pyrone were investigated, manifesting its ambident property with a series of electronically and sterically distinct dienophiles.

Key words

3-methyl-4-methylene-5-carbonylmethylene-2-pyrone - synthesis - Diels–Alder cycloaddition - regioselectivity - stereo­selectivity - sesquiterpenoids

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• 15 Representative Procedure A mixture of crude 2-pyrone 3 (32.8 mg, 0.20 mmol), methyl acrylate (69.0 mg, 0.80 mmol), and 2,6-di-tert-butyl-4-methylphenol (BHT, 8.8mg, 0.04 mmol) in anhydrous CH₂Cl₂ (1 mL) was heated at 100 °C in a sealed tube for 10 h. After the reaction, the reaction mixture was concentrated and purified by flash column chromatography on silica gel (PE–EtOAc, 4:1 to 2:1) to give 30.5 mg (0.12 mmol) of 5-endo-12a and 10.2 mg (0.04 mmol) of 6-endo-12b, in yields of 61% and 20%, respectively. Compound 5-endo-12a: IR (thin film): 2951, 1750, 1701, 1641 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 5.55 (dd, J = 3.9, 1.2 Hz, 1 H), 3.69 (s, 3 H), 2.95 (dd, J = 10.0, 4.0 Hz, A of AB, 1 H), 2.85–2.78 (m, 1 H), 2.77–2.71 (m, 2 H), 2.64–2.61 (m, 2 H), 1.79 (ddd, J = 13.6, 4.0, 1.2 Hz, B of AB, 1 H), 1.58 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 199.8, 179.6, 172.1, 171.9, 142.8, 69.4, 52.3, 49.7, 43.0, 37.0, 32.9, 26.2, 12.7. HRMS (ES): m/z calcd for C₁₃H₁₈NO₅ [M + NH₄]⁺: 268.1179; found: 268.1176. Compound 6-endo-12b: IR (thin film): 2951, 1705, 1642 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 5.72 (d, J = 3.6 Hz, 1 H), 3.68 (s, 3 H), 3.52 (m, 1 H), 2.73–2.72 (m, 2 H), 2.60–2.57 (m, 2 H), 2.11 (dd, J = 13.2, 9.2 Hz, A of A B, 1 H), 2.04 (dd, J = 13.2, 5.6 Hz, B of A B, 1 H), 1.58 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 199.5, 181.0, 173.3, 170.6, 141.9, 70.8, 52.9, 47.5, 44.4, 37.0, 31.6, 25.1, 14.5. HRMS (ES): m/z calcd for C₁₃H₁₈NO₅ [M + NH₄]⁺: 268.1179; found: 268.1176.