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Synlett 2008(14): 2115-2118  
DOI: 10.1055/s-2008-1078244
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Synthesis of Isoxazoline-Fused Bicyclic Enediynes via Intramolecular Nitrile Oxide-Alkene Cycloaddition

Amit Basak*, Runa Pal
Department of Chemistry, Indian Institute of Technology, Kharagpur 721302, India
e-Mail: absk@chem.iitkgp.ernet.in;
Further Information

Publication History

Received 30 April 2008
Publication Date:
31 July 2008 (online)

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Abstract

The intramolecular nitrile oxide-alkene cycloaddition has been studied in an enediyne system. It has been shown to be an efficient method for one-step synthesis of isoxazoline-fused bicyclic enediynes. The thermal reactivity of these enediynes is similar to the isoxazolidine-fused counterparts, thus ruling out any significant effect by the bridgehead double bond.

Key word

enediyne - cycloaddition - Bergman cyclization - intra­molecular - activation

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ArgusLab version 4.0.1, Thomson and Planaria Software LLC.

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Selected Spectroscopic Data: Compound 11: ¹H NMR (400 MHz): δ = 1.22 (t, J = 7.0 Hz, 3 H, COOCH2CH 3), 2.64-2.76 (m, 1 H, CHCH 2COOEt), 3.20-3.22 (m, 2 H, CCCH 2CH), 3.82-3.89 (m, 2 H, CCCHCH2NO2), 4.26 (q, J = 7.2 Hz, 2 H, COOCH 2CH3), 4.55-4.66 (m, 2 H, CHCH 2NO2), 5.13 (dd, J = 1.6, 10.0 Hz, 1 H, CH2CHCH 2), 5.40 (dd, J = 2.0, 17.2 Hz, 1 H, CH2CHCH 2), 5.84-5. 90 (m, 1 H, CH2CH=CH2), 7.12-7.19 (m, 2 H, ArH), 7.28-7.38 (m, 2 H, ArH). ¹³C NMR (100 MHz): δ = 0.96, 14.1, 30.1, 31.7, 36.4, 61.2, 81.2, 83.3, 88.6, 90.9, 115.7, 125.1, 126.2, 126.5, 128.2, 128.7, 130.8, 140.7, 170.0. MS (ESI): m/z = 325 [M+].
Compound 1A: ¹H NMR (400 MHz): δ = 1.29 (t, J = 6.0 Hz, 3 H, COOCH2CH 3), 2.68 (dd, J = 7.2, 12.8 Hz, 1 H, Hg), 2.74 (dd, J = 3.2, 14.8 Hz, 1 H, Hd), 2.83 (dd, J = 5.6, 12.8 Hz, 1 H, Hh), 2.91 (dd, J = 1.6, 14.8 Hz, 1 H, He), 3.20 (dd, J = 8.4, 13.2 Hz, 1 H, Hc), 3.60 (dd, J = 2.8, 13.2 Hz, 1 H, Hb), 4.20 (q, J = 5.6 Hz, 2 H, COOCH 2CH3), 4.45 (dd, J = 1.6, 5.6 Hz, 1 H, Hf), 4.93-4.97 (m, 1 H, Ha), 7.21-7.29 (m, 2 H, ArH), 7.34-7.36 (m, 2 H, ArH). ¹³C NMR (100 MHz): δ = 14.1, 27.3, 28.7, 29.6, 35.7, 36.3, 61.2, 81.6, 85.0, 88.4, 92.0, 124.9, 127.6, 128.1, 128.2, 129.1, 130.8, 155.5, 169.7. MS (ESI): m/z = 330 [M + Na+]. HRMS: m/z calcd for C19H18NO3 [M + H+]: 308.3512; found: 308.3510.
Compound 1B: ¹H NMR (400 MHz): δ = 1.28 (t, J = 5.6 Hz, 3 H, COOCH2CH 3), 2.72 (dd, J = 3.4, 14.6 Hz, 1 H, He), 2.91 (dd, J = 3.2, 14.6 Hz, 1 H, Hd), 2.95 (dd, J = 1.6, 14.4 Hz, 1 H, Hg), 3.23 (dd, J = 4.8, 14.4 Hz, 1 H, Hh), 3.30 (dd, J = 7.2, 14.0 Hz, 1 H, Hb), 3.63 (dd, J = 2.8, 14.0 Hz, 1 H, Hc), 3.96 (dd, J = 4.8, 7.2 Hz, 1 H, Hf), 4.20 (q, J = 2.4 Hz, 2 H, COOCH 2CH3), 4.92-4.96 (m, 1 H, Ha), 7.20-7.29 (m, 2 H, ArH), 7.34-7.36 (m, 2 H, ArH). ¹³C NMR (100 MHz): δ = 14.1, 27.2, 28.5, 29.6, 35.6, 39.9, 60.9, 81.5, 84.9, 88.6, 92.3, 125.0, 127.6, 128.0, 128.3, 129.1, 130.8, 156.3, 171.0. MS (ESI): m/z 330 [M + Na+]. HRMS: m/z calcd for C19H18NO3 [M + H+]: 308.3512; found: 308.3509.