P(NMe₂)₃-Mediated Domino Cyclization/Functionalization of Dicyanoalkenes

Abstract

A P(NMe₂)₃-mediated domino reaction between dicyanoalkenes and benzoylformates has been developed. By switching between isatin- and tetralone-derived dicyanoalkenes, the protocol divergently furnishes either spirocyclopropyl oxindoles or α-functionalized dicyanoalkenes in up to 99% yield under mild conditions. Gram-scale experiments and a broad substrate scope highlight the synthetic utility of the transformation.

Keywords

Dicyanoalkenes - Benzoylformates - Spirocyclopropyl oxindoles - α-Functionalized dicyanoalkenes - P(NMe₂)₃-mediated

Publication History

Received: 10 November 2025

Accepted after revision: 05 December 2025

Accepted Manuscript online:
05 December 2025

Article published online:
24 December 2025

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• 9 General experimental procedures for synthesis of compounds 3. To an ordinary vial fitted with a magnetic stir bar were added dicyanoalkene 1 (0.1 mmol, 1.0 equiv), benzoylformate 2 (0.12 mmol, 1.2 equiv), P(NMe₂)₃ (0.12 mmol, 1.2 equiv) and EA (1.0 mL). The mixture was stirred at room temperature for 12 h, then loaded directly onto a short silica-gel column and purified by flash chromatography to afford product 3.
• 10 Ethyl 3,3-dicyano-1′-methyl-2′-oxo-2-phenylspiro[cyclopropane-1,3′-indoline]-2-carboxylate (3a) white solid (35.7 mg, 96% yield); m.p. 152.1–153.9 °C. ¹H NMR (600 MHz, CDCl₃) δ 7.51–7.46 (m, 1H), 7.46–7.40 (m, 3H), 7.40–7.28 (m, 2H), 7.08–6.97 (m, 1H), 6.95–6.85 (m, 1H), 6.17 (dd, J = 7.8, 1.2 Hz, 1H), 4.36–4.29 (m, 1H), 4.28–4.17 (m, 1H), 3.39 (s, 3H), 1.30 (t, J = 7.1 Hz, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 166.9, 163.6, 145.3, 131.0, 130.7, 130.5, 129.3, 127.0, 126.3, 122.7, 117.9, 110.3, 109.8, 109.3, 63.7, 51.5, 45.2, 27.3, 24.2, 13.7. HRMS (ESI) calcd for C₂₂H₁₇N₃O₃Na⁺ (M+Na)⁺ 394.11621, found 394.11624.
• 11 General experimental procedures for synthesis of compounds 5. In an ordinary vial charged with a magnetic stirring bar, dicyanoalkenes 4 (0.1 mmol, 1.0 equiv), benzoylformates 2 (0.12 mmol, 1.2 equiv), P(NMe₂)₃ (0.12 mmol, 1.2 equiv) and EA (1.0 mL) was added, and then the mixture was stirred at r.t. for 12 h. the products 5 were isolated by flash chromatography on silica gel.
• 12 Ethyl 3,3-dicyano-3-(3,4-dihydronaphthalen-1-yl)-2-phenylpropanoate (5a) White solid (34.2 mg, 98% yield); m.p. 136.2–137.6 °C. 1H NMR (600 MHz, CDCl₃) δ 7.82 (dd, J = 7.8, 1.1 Hz, 1H), 7.40–7.33 (m, 2H), 7.32–7.24 (m, 4H), 7.12–7.05 (m, 2H), 6.48 (dd, J = 5.7, 4.1 Hz, 1H), 4.73 (s, 1H), 4.38–4.17 (m, 2H), 2.69–2.54 (m, 1H), 2.46–2.31 (m, 1H), 2.30–2.08 (m, 2H), 1.25 (t, J = 7.1 Hz, 3H). 13C NMR (151 MHz, CDCl3) δ 168.3, 137.9, 135.3, 130.6, 129.7, 129.6, 129.5, 128.9, 128.9, 128.6, 127.1, 126.3, 123.2, 114.5, 113.5, 62.7, 54.3, 44.6, 27.6, 23.3, 14.1. HRMS (ESI) calcd for C₂₃H₂₀N₂O₂Na⁺ (M+Na)⁺ 379.14170, found 379.14185.
• 13 Scale-up experiment. To a 100-mL round-bottom flask containing a magnetic stir bar were added sequentially dicyanoalkene 1a or 4a (5.0 mmol, 1.0 equiv), benzoylformate 2a (6.0 mmol, 1.2 equiv), P(NMe₂)₃ (6.0 mmol, 1.2 equiv) and EA (50 mL). The resulting mixture was stirred at room temperature for 12 h. The residue was purified by flash column chromatography on silica gel to afford the corresponding product 3a (90% yield) or 5a (95% yield).