A Simple Aluminum Bromide-Promoted Diastereoselective Synthesis of Panduratin A Derivatives

Abstract

A facile diastereoselective synthesis of panduratin A derivatives using commercially available aluminum(III) bromide is reported. The effect of substituents on the Diels–Alder reaction of various trans-chalcones with (E)-ocimene was investigated. A series of panduratin A derivatives were prepared in moderate to good yields.

Key words

panduratin A - ocimene - Diels–Alder reaction - chalcones - dienes - aluminum bromide

• References and Notes

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• 18 Panduratin A Derivatives 3a–r; General ProcedureA 1.0 M solution of AlBr₃ in CH₂Br₂ (30 mol%) was added to a solution of the appropriate trans-chalcone (1 equiv) in anhyd toluene or CH₂Cl₂ (2 mL/mmol) at r.t. (28 °C) under N₂. (E)-Ocimene (5 equiv) was added, and the mixture was stirred at r.t. for 24 h or until all the chalcone was consumed. The mixture was then poured into ice–water acidified with 3 N aq HCl to pH 2–3. The resulting mixture was extracted with EtOAc, and the organic phase was dried (Na₂SO₄) and concentrated under reduced pressure. The crude product was purified by column chromatography (silica gel, 5–20% EtOAc–hexane).[3-Methyl-2-(3-methylbut-2-en-1-yl)-6-phenylcyclohex-3-en-1-yl](phenyl)methanone (3)Pale brown solid; yield: 124 mg (72%); mp 90–92 °C. ¹H NMR (400 MHz, CDCl₃): δ = 1.38 (s, 6 H), 1.70 (s, 3 H), 1.97–2.09 (m, 2 H), 2.11–2.18 (m, 1 H), 2.34–2.39 (m, 2 H), 3.36 (td, J = 10.5, 6.4 Hz, 1 H), 4.08 (dd, J = 10.5, 5.0 Hz, 1 H), 4.74 (t, J = 6.9 Hz, 1 H), 5.41 (br s, 1 H), 6.99 (t, J = 6.9 Hz, 1 H), 7.09–7.14 (m, 4 H), 7.32 (t, J = 7.8 Hz, 2 H), 7.40 (t, J = 7.3 Hz, 1 H), 7.79 (d, J = 7.8 Hz, 2 H). ¹³C NMR (100 MHz, CDCl₃): δ = 17.7, 22.8, 25.6, 28.7, 35.0, 36.9, 42.8, 50.3, 121.3, 123.7, 125.7, 127.0, 127.9, 128.3, 128.4, 131.9, 132.5, 136.5, 137.4, 146.3, 200.6. HRMS (ESI): m/z [M + H]⁺ calcd for C₂₅H₂₉O: 345.2218; found: 345.2225.(2-Chlorophenyl)[3-methyl-2-(3-methylbut-2-en-1-yl)-6-phenylcyclohex-3-en-1-yl]methanone (3a)Yellow oil; yield: 32 mg (17%). ¹H NMR (400 MHz, CDCl₃): δ = 1.50 (s, 3 H), 1.58 (s, 3 H), 1.68 (s, 3 H), 2.11–2.22 (m, 2 H), 2.25–2.32 (m, 2 H), 2.39–2.46 (m, 1 H), 3.34 (td, J = 9.8, 7.1 Hz, 1 H), 3.96 (dd, J = 10.2, 4.2 Hz, 1 H), 4.97 (t, J = 6.6 Hz, 1 H), 5.40 (br s, 1 H), 7.04–7.08 (m, 1 H), 7.14–7.30 (m, 8 H). ¹³C NMR (100 MHz, CDCl₃): δ = 18.0, 23.1, 25.8, 29.0, 33.8, 37.4, 40.6, 55.3, 121.0, 123.6, 126.0, 126.6, 127.7, 128.2, 129.4, 130.8, 131.5, 131.5, 132.0, 136.9, 139.0, 145.7, 202.7. HRMS (ESI): m/z [M + H]⁺ calcd for C₂₅H₂₈ ³⁵ClO: 379.1829; found: 379.1831.