Synthesis of Linear Tetraquinanes by [3+2] Cycloaddition, Chemoselective Allylation of 7-Ketonorbornene, and Ring-Rearrangement Metathesis as Key Steps

Abstract

A nine-step synthetic sequence to linear tetraquinanes involving [3+2] cycloaddition, chemoselective allylation, and ring-rearrangement metathesis as key steps is reported. A chemoselective allylation of 7-ketonorbornene was realized for the first time by using indium powder and allyl bromide. By this method, norbornene ketones can be selectively allylated in the presence of a cyclopentanone moiety to give good yields of monoallylated Barbier-type products.

Key words

[3+2]-cycloaddition - allylation - polyquinanes - tetraquinane - ring-rearrangement metathesis

Publication History

Received: 09 June 2022

Accepted after revision: 28 July 2022

Article published online:
09 September 2022

• References and Notes

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• 13 (2′S,3a′R,3b′S,4′S,7′S,7a′R,8a′S)-4′,8a′-Dibromo-2′-(triisopropylsilyl)-2′,3′,3a′,3b′,4′,7′,7a′,8a′-octahydrospiro{[1,3]dioxolane-2,9′-[4,7]methanocyclopenta[a]inden}-8′(1′H)-one (16)Compound 15 (3 g, 8.2 mmol) was stirred in anhyd CH₂Cl₂ (50 mL). TiCl₄ (4.7 g, 24.8 mmol) and allyl(triisopropyl)silane (2.4 g, 12.4 mmol) were added sequentially at rt under an inert atmosphere and the mixture was stirred for 12 h. The reaction was quenched with aq NH₄Cl, and the mixture was extracted with CH₂Cl₂ (×3). The combined organic layer was washed with H₂O, dried (Na₂SO₄), and concentrated. The crude product was purified by column chromatography (silica gel, 10% EtOAc–PE) to give a white solid; yield: 2.5 g (54%); mp 108–110 °C. ¹H NMR (400 MHz, CDCl₃): δ = 6.25–6.21 (m, 2 H), 4.25–4.15 (m, 2 H), 4.03–3.98 (m, 1 H), 3.94–3.90 (m, 1 H), 3.28–3.25 (m, 1 H), 2.99–2.96 (m, 1 H), 2.75 (dd, J = 5.51, 3.87 Hz, 1 H), 2.68–2.65 (m, 1 H), 2.54–2.49 (m, 1 H), 2.36–2.27 (m, 2 H), 1.97 (dd, J = 7.73, 5.15 Hz, 1 H), 1.584–1.581 (m, 1 H), 1.08–1.05 (m, 21 H). ¹³C NMR (100 MHz, CDCl₃): δ = 215.4, 137.5, 134.6, 125.8, 71.4, 69.3, 66.6, 65.8, 54.6, 54.3, 53.3, 47.8, 47.4, 39.2, 24.8, 19.28, 19.25, 11.46. DEPT135 (100 MHz, CDCl₃): CH, CH₃ (δ = 137.5, 134.6, 54.6, 54.3, 53.2, 47.4, 24.8, 19.28, 19.25, 11.4); CH₂ (δ = 66.6, 65.8, 47.8, 39.2). HRMS (ESI): m/z [M + Na]⁺ calcd for C₂₄H₃₆Br₂NaO₃Si: 581.0693; found: 581.0691.
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• 15 (2′S,3a′R,3b′R,4′R,7′S,7a′S,8a′R)-2′-(Triisopropylsilyl)-2′,3′,3a′,3b′,4′,7′,7a′,8a′-octahydrospiro{[1,3]dioxolane-2,9′-[4,7]methanocyclopenta[a]inden}-8′(1′H)-one (17) A solution of 16 (2 g, 3.5 mmol) in anhyd toluene was treated with AIBN (10 mol%). The reaction vessel was covered with aluminum foil to maintain dark conditions. Bu₃SnH (3 g, 10.7 mmol) was added dropwise, and the mixture was refluxed at 110 °C for 4 h until the reaction was complete (TLC). The mixture was then cooled and the solvent was evaporated under reduced pressure. The resulting crude mixture was purified by column chromatography (silica gel, 10% EtOAc–PE) to give a pale-green liquid; yield: 962 mg (67%). ¹H NMR (400 MHz, CDCl₃): δ = 6.29–6.27 (m, 1 H), 6.17–6.14 (m, 1 H), 3.94–3.87 (m, 2 H), 3.84–3.80 (m, 2 H), 3.02–2.99 (m, 1 H), 2.96–2.93 (m, 1 H), 2.91–2.89 (m, 1 H), 2.68–2.64 (m, 1 H), 2.36–2.29 (m, 2 H), 2.08–2.03 (m, 1 H), 1.88–1.85 (m, 2 H), 1.71–1.67 (m, 1 H), 1.60 (s, 1 H), 1.05–1.03 (m, 21 H). ¹³C (100 MHz, CDCl₃): δ = 226.1, 133.9, 133.7, 127.0, 65.1, 64.6, 58.6, 55.0, 51.5, 50.0, 47.0, 42.9, 40.5, 36.2, 24.4, 19.3, 11.5. DEPT135 (100 MHz, CDCl₃): CH, CH₃ ( δ = 133.9, 133.7, 58.6, 55.0, 51.5, 49.9, 47.0, 42.9, 24.4, 19.3, 11.5); CH₂ (δ = 65.1, 64.6, 40.5, 36.2). HRMS (ESI) m/z [M + H]⁺ calcd for C₂₄H₃₉O₃Si: 403.2663; found: 403.2660.
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• 17 (2S,3aR,3bS,4R,7S,7aS,8aR,9S)-9-Allyl-9-hydroxy-2-(triisopropylsilyl)-2,3,3a,3b,4,7,7a,8a-octahydro-4,7-methanocyclopenta[a]inden-8(1H)-one (19) A solution of compound 18 (100 mg, 0.27 mmol) in 3:1 THF–H₂O (20 mL) was treated with allyl bromide (267 mg, 2.2 mmol) and In powder (96 mg, 0.83 mmol), and the mixture was stirred at rt for 6 h. When the reaction was complete, the mixture was filtered through Celite and extracted with EtOAc (×3). The combined organic layer was washed with H₂O, dried (Na₂SO₄), and concentrated. The crude product was purified by column chromatography (silica gel, 10% EtOAc–PE) to give a pale-yellow liquid; yield: 104 mg (93%). ¹H NMR (500 MHz, CDCl₃): δ = 6.16–6.14 (m, 1 H), 6.04–6.02 (m, 1 H), 5.76–5.67 (m, 1 H), 5.16–5.09 (m, 2 H), 3.16–3.13 (m, 1 H), 2.83–2.78 (m, 3 H), 2.46–2.34 (m, 5 H), 2.08–2.04 (m, 1 H), 1.97 (br s, 1 H), 1.86–1.85 (m, 2 H), 1.71–1.67 (m, 1 H), 1.03 (s, 21 H). ¹³C (125 MHz, CDCl₃): δ = 227.6, 134.94, 134.91, 134.7, 119.5, 95.0, 59.1, 56.4, 54.1, 53.5, 48.2, 42.7, 40.6, 37.0, 36.2, 24.4, 19.3, 11.5. DEPT135 (125 MHz, CDCl₃): CH, CH₃ (δ = 134.94, 134.91, 134.7, 59.1, 56.4, 54.1, 53.5, 48.2, 42.7, 24.4, 19.3, 11.5); CH₂ (δ = 119.5, 40.6, 37.0, 36.2). HRMS (ESI) m/z [M + H]⁺ calcd for C₂₅H₄₁O₂Si: 401.2877; found: 401.2876.
• 18 Preliminary single-crystal X-ray diffraction data for compound 22b are given in the Supporting Information.