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Synlett 2012(2): 227-232  
DOI: 10.1055/s-0031-1290070
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Exploring α-Chromonyl Nitrones as 1,5-Dipoles

Kathrin Wittsteina,b, Ana B. Garcíaa, Markus Schürmannc, Kamal Kumar*a,b
a Max-Planck-Institut für Molekulare Physiologie, Otto-Hahn-Str. 11, 44227 Dortmund, Germany
Fax: +49(231)1332496; e-Mail: Kamal.Kumar@mpi-dortmund.mpg.de;
b Technische Universität Dortmund, Fachbereich Chemie, Chemische Biologie, 44221 Dortmund, Germany
c Technische Universität Dortmund, Anorganische Chemie, 44221 Dortmund, Germany
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Publikationsverlauf

Received 17 October 2011
Publikationsdatum:
03. Januar 2012 (online)

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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

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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: +44 (1223)336033; e-mail: deposit@ccdc.cam.ac.uk]

13

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

14

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

15

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 C23H19Cl³7NO6: 442.08659; found: 442.08630