Biomimetic Total Synthesis of 6a,7,8,9,10,10a-Hexahydro-3,6,9-trimethyl-6-(4-methylpent-3-en-1-yl)-1,9-epoxy-6H-dibenzo-[b,d]pyran and Its Diastereoisomer

Abstract

The first total synthesis of 6a,7,8,9,10,10a-hexahydro-3,6,9-trimethyl-6-(4-methylpent-3-en-1-yl)-1,9-epoxy-6H-dibenzo[b,d]pyran and its diastereoisomer via tandem pericyclic reactions were achieved in one step. Our biomimetic strategy features a sequential Aldol-type addition, 6π electrocyclization, and hetero-Diels–Alder cycloaddition, where three rings, two C–C bonds, and two C–O bonds were spontaneously constructed in a highly efficient way.

Key words

biomimetic - total synthesis - tandem pericyclic reactions - 6π electrocyclization - hetero-Diels–Alder cycloaddition

• References and Notes


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• 11 Diastereoselective Total Synthesis of 3,6,9-Trimethyl-6-(4-methylpent-3-en-1-yl)-1,9-epoxy-6H-dibenzo[b,d]pyran (1) (2E,6E)-Farnesal (440 mg, 2 mmol) and 5-methylbenzene-1,3-diol (372 mg, 3 mmol) were added to pyridine (15 mL) and the mixture was refluxed rigorously at 160 °C for 16 h under argon. The reaction mixture was cooled to r.t., and the solvent was evaporated in vacuo. The residue was purified by column chromatography on silica gel with the appropriate mixture of hexane and EtOAc to give 6a,7,8,9,10,10a-hexahydro-3,6,9-trimethyl-6-(4-methylpent-3-en-1-yl)-1,9-epoxy-6H-dibenzo[b,d]pyran (1, 476 mg, 73%) as pale yellow liquid. IR (film): ν_max = 1621, 1067 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 6.31 (s, 1 H), 6.27 (s, 1 H), 5.17 (t, J = 7.0 Hz, 1 H), 2.85 (s, 1 H), 2.25 (s, 3 H), 2.21–2.19 (m, 1 H), 2.17 (dd, J = 4.5, 3.3 Hz, 1 H), 2.08 (ddd, J = 11.6, 5.3, 2.9 Hz, 2 H), 1.95–1.85 (m, 1 H), 1.82–1.73 (m, 3 H), 1.71 (s, 3 H), 1.65 (s, 3 H), 1.46–1.38 (m, 1 H), 1.37 (s, 3 H), 0.96 (s, 3 H), 0.87 (dt, J = 6.6, 5.1 Hz, 1 H), 0.63 (ddd, J = 25.0, 13.3, 6.1 Hz, 1 H). ¹³C NMR (101 MHz, CDCl₃): δ = 156.7, 156.5, 137.2, 131.8, 124.3, 114.3, 110.7, 109.6, 85.8, 74.5, 45.3, 42.1, 37.5, 35.3, 29.1, 27.9, 25.7, 22.9, 22.2, 21.7, 20.9, 17.7. HRMS (APCI): m/z calcd for C₂₂H₃₁O₂: 327.2319; found: 327.2305 [M + H].