Exploring α-Chromonyl Nitrones as 1,5-Dipoles

Abstract

N-Phenyl-C-chromonyl nitrones 1 and the allenoate zwitterion 2, generated by addition of phosphine to acetylenedicarboxylates, undergo a cascade reaction sequence involving an unprecedented [5+3] annulation followed by deoxygenative rearrangement leading to dihydropyridine-fused benzopyrones. Unusual electronic control by the N-substituents of 1 directs the annulation pathway, leading to two different ring-systems.

Keywords

nitrones - dipolar cycloadditions - acetylene carboxylates - cascade reactions - zwitterions

References and Notes

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12

Crystallographic data for 8a has been deposited at the Cambridge Crystallographic Data Centre (CCDC-848674). Copies of the data can be obtained free of charge at www.ccdc.cam.uk/data_request/cif or from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ [fax: [phone]; e-mail: [e-mail]]

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Representative procedure for the synthesis of dihydro-pyridine fused benzopyrones 8a: To a solution of nitrone 1f-i (94 mg, 0.34 mmol) in anhydrous CH₂Cl₂ (10 mL) was added dimethyl acetylenedicarboxylate (83 µL, 0.67 mmol, 2 equiv), followed by triphenylphosphine (88 mg, 0.4 mmol, 1.2 equiv). The resulting mixture was stirred at r.t. for 48 h. The solvent was evaporated under reduced pressure and the residue was purified by flash column chromatography (EtOAc-petroleum ether, 15-18%) to give 8a (48 mg, 0.12 mmol, 36% yield) as a yellow solid

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Compound 8a: R _f = 0.35 (EtOAc-petroleum ether, 40%); mp 226-236 ˚C; ^¹H NMR (400 MHz, CDCl₃): δ = 8.31 (d, J = 1.8 Hz, 1 H), 7.87 (d, J = 1.9 Hz, 1 H,), 7.51-7.44 (m, 2 H), 7.41-7.34 (m, 4 H), 7.21 (d, J = 8.0 Hz, 1 H), 6.10 (d, J = 1.7 Hz, 1 H), 3.87 (s, 3 H), 3.74 (s, 3 H), 2.39 (s, 3 H); ^¹³C NMR (100 MHz, CDCl₃): δ = 175.54, 170.29, 164.85, 156.97, 154.45, 147.13, 143.13, 135.75, 133.75, 129.83, 127.71, 125.89, 121.47, 120.24, 117.34, 105.59, 84.38, 61.98, 53.11, 51.62, 20.64; HRMS (ESI): m/z [M + H]⁺ calcd for C₂₃H₂₀NO₆: 406.12851; found: 406.12806

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Compound 8d: R _f = 0.37 (EtOAc-petroleum ether, 30%); ^¹H NMR (400 MHz, CDCl₃): δ = 8.30 (d, J = 1.7 Hz, 1 H), 8.03 (s, 1 H), 7.48 (dd, J = 7.7 Hz, 2 H), 7.40-7.32 (m, 3 H), 7.21 (s, 1 H), 6.10 (d, J = 1.7 Hz, 1 H), 3.87 (s, 3 H), 3.74 (s, J = 5.1 Hz, 3 H), 2.45 (s, 3 H); ^¹³C NMR (100 MHz, CDCl₃): δ = 174.24, 170.18, 164.68, 155.54, 154.47, 147.20, 143.81, 143.09, 130.19, 129.89, 127.88, 126.06, 121.55, 119.81, 119.66, 105.13, 84.92, 62.02, 53.19, 51.71, 20.70; HRMS (ESI): m/z [M + H]⁺ calcd for C₂₃H₁₉ClNO₆: 440.08954; found: 440.08909; m/z [M + H]⁺ calcd for C₂₃H₁₉Cl^³7NO₆: 442.08659; found: 442.08630