Cyclopropane Intermediates from Insertion Reactions of Platinum–Carbenes: A Route to Heterospiranes

Abstract

Heteroaromatic-anchored enynals with a pendent alkene group were successfully cyclized through a Huisgen-type [3+2] cycloaddition to give a tetracyclic Pt–carbene complex that underwent insertion into the C–H bond in the β-position to give fused cyclopropanes that are otherwise inaccessible. On heating, the cyclopropanes smoothly rearranged to form the corresponding heterospiranes with excellent levels of stereoselectivity and high yields.

Key words

cyclization - platinum catalysis - pyrylium ions - carbenes - heterospiranes

• References and Notes

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• 10 Heterocyclopropane 7a; Typical Procedure A new 5 mL test tube was charged with the 2-alkynylnicotinaldehyde 6a (0.40 mmol), PtCl₂(PPh₃)₂ (11 mg, 0.04 mmol), and anhyd toluene (1.5 mL) at 0 °C under argon. The mixture was stirred for 4 h in a preheated oil bath (120 °C). When the reaction was complete (TLC), the solvent was removed under vacuum, and the crude product was purified by flash column chromatography (silica gel, hexane–EtOAc) to give a yellow oil; yield: 169 mg (94%); R_f = 0.41 (EtOAc–hexane, 1:4). IR (NaCl): 2980, 1732, 1440, 1244 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 7.92 (d, J = 8.0 Hz, 2 H), 7.49–7.46 (m, 2 H), 7.42 (d, J = 7.2 Hz, 1 H), 7.24 (d, J = 10.0 Hz, 1 H), 5.13 (d, J = 5.6 Hz, 1 H), 4.30–4.16 (m, 4 H), 3.12 (d, J = 15.2 Hz, 1 H), 2.45 (s, 1 H), 2.30 (d, J = 14.4 Hz, 2 H), 2.18–2.11 (m, 1 H), 1.93–1.78 (m, 3 H), 1.42 (d, J = 11.6 Hz, 1 H), 1.30 (t, J = 7.2 Hz, 3 H), 1.26 (t, J = 7.2 Hz, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 171.5, 170.8, 157.2, 154.6, 148.8, 148.7, 144.8, 144.7, 135.7, 135.6, 128.9, 128.8, 128.8, 128.5, 118.3, 118.1, 73.8, 61.9, 61.7, 61.7, 53.3, 33.7, 31.4, 30.7, 26.5, 22.8, 21.6, 14.2, 14.1. HRMS (ESI): m/z [M + Na]⁺ calcd for C₂₆H₂₆FNNaO₅: 474.1688; found: 474.1691.
• 11 Spiro(cyclohexane-1,7′-quinoline) 8a; Typical Procedure A new 5 mL test tube was charged with the 2-alkynylnicotinaldehyde 6a (0.40 mmol), PtCl₂(PPh₃)₂ (11 mg, 0.04 mmol), and anhyd xylene (1.5 mL) at 0 °C under argon. The mixture was stirred for 1 h in a preheated oil bath (150 °C) until the reaction was complete (TLC). The solvent was removed under vacuum, and the crude product was purified by flash column chromatography (silica gel, hexane–EtOAc) to give a yellow oil; yield: 140 mg (78%); R_f  = 0.33 (EtOAc–hexane, 1:4). IR (NaCl): 2981, 1731, 1441, 1249, 1249 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 7.96 (d, J = 8.4 Hz, 2 H), 7.49–7.39 (m, 3 H), 7.13 (d, J = 11.2 Hz, 1 H), 6.52 (d, J = 9.2 Hz, 1 H) , 6.15 (d, J = 9.6 Hz, 1 H), 4.27–4.19 (m, 4 H), 3.36 (d, J = 16.0 Hz, 1 H), 3.10 (d, J = 16.0 Hz, 1 H), 2.92 (ABq, Δδ = 38.8 Hz, J = 15.2 Hz, 2 H), 2.44–2.28 (m, 2 H), 1.91–1.85 (m, 2 H), 1.26 (t, J = 7.2 Hz, 6 H). ¹³C NMR (100 MHz, CDCl₃): δ = 207.0, 170.4, 170.1, 158.0, 155.4, 149.6, 149.5, 143.8, 143.7, 135.4, 135.4, 132.7, 132.6, 129.2, 129.1, 128.9, 128.9, 128.8, 128.8, 128.6, 127.9, 127.8, 126.3, 121.1, 120.9, 62.2, 62.2, 57.5, 50.6, 42.5, 38.4, 32.0, 26.0, 14.1. HRMS (ESI): m/z [M + Na]⁺calcd for C₂₆H₂₆FNNaO₅: 474.1688; found: 474.1695.