Synthesis of a Propellane-Type 5/5/6-Tricyclic System by Tandem-Metathesis: A New Approach to a Quadranoid Skeleton

Abstract

We disclose a useful synthetic method for preparing the propellane-type 5/5/6-tricyclic system that is present in diquinane-based natural products such as quadrone, terrecyclic acid A, or terrecyclol. The method involves an LDA-mediated regio- and stereoselective allylation and a tandem metathesis as key steps. The target molecules were assembled in just two steps starting from a readily available building block, a 3β-vinyl tricyclic ketone prepared from endo-dicyclopentadiene-1-one. All the compounds prepared were characterized by NMR analyses and/or chemical methods. The synthetic methods demonstrated here are useful in syntheses of quadranoid-type natural products.

Keywords

allylation - olefin metathesis - diquinanes - tricyclic compounds - dicyclopentadienone - natural products

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• 21 (1S,2R,4S,5S,6S)-2,4-Divinyltricyclo[4.3.2.0^1,5]undec-7-en-10-one (14) A stirred solution of compound 15 (50 mg, 0.233 mmol) in CH₂Cl₂ (50 mL) was purged sequentially with N₂ gas and ethylene gas for 10 min each. G-II catalyst (20 mg, 0.023 mmol; 10 mol%) was added in one portion at rt under an ethylene atmosphere, and purging was continued for another 5–10 min. The mixture was then stirred at rt under ethylene for 8 h. When the reaction was complete (TLC), the volatiles were removed under reduced pressure, and the crude product was purified by column chromatography (silica gel, 1.0–1.5% EtOAc–PE) to give a colorless liquid; yield: 44 mg (88%); R_f = 0.61 (silica gel-coated 4.0 × 2.0 cm glass TLC plate, 2.0% EtOAc–PE; double run). IR (neat): 3074, 3026, 2923, 2877, 1737, 1636, 1454, 1429, 1412, 1325, 1156, 1098, 1070, 995, 955, 911, 775, 752, 721, 700, 676, 521 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 6.25 (tdd, J = 17.83, 11.78, 8.52 Hz, 1 H), 6.12–6.08 (m, 1 H), 5.99 (ddd, J = 16.81, 10.58, 6.00 Hz, 1 H), 5.52 (ddd, J = 9.31, 3.77, 2.58 Hz, 1 H), 5.09–5.04 (m, 4 H), 3.04–2.95 (m, 1 H), 2.77 (t, J = 5.94 Hz, 1 H), 2.62 (d, J = 11.99 Hz, 1 H), 2.52–2.45 (m, 1 H), 2.39–2.31 (m, 2 H), 2.18 (dq, J = 17.70, 2.48 Hz, 2 H), 2.04 (ddd, J = 13.16, 7.61, 5.92 Hz, 1 H), 1.45 (dd, J = 23.92, 12.70 Hz, 1 H). ¹³C{¹H} NMR (100 MHz, CDCl₃): δ = 223.2 (CO), 139.1 (CH), 137.4 (CH), 136.4 (CH), 126.1 (CH), 115.5 (CH₂), 115.4 (CH₂), 61.2 (C), 54.1 (CH), 51.8 (CH), 49.3 (CH₂), 41.1 (CH), 38.4 (CH₂), 38.3 (CH₂), 34.3 (CH). HRMS (ESI, Q-ToF): m/z [M + K]⁺ calcd for C₁₅H₁₈KO: 253.0989; found 253.0989.