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Synlett 2010(7): 1128-1132  
DOI: 10.1055/s-0029-1219588
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

A Facile, One-Pot Synthesis of Functionalized Spiro-Oxindoles via Vinylogous Aldol Reaction of Vinyl Malononitriles with Isatin Derivatives in Aqueous ­Media

Thelagathoti Hari Babu, K. Karthik, Paramasivan T. Perumal*
Organic Chemistry Division, Central Leather Research Institute, Adyar, Chennai 600 020, India
Fax: +91(44)24911589; e-Mail: ptperumal@gmail.com;
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Publikationsverlauf

Received 2 February 2010
Publikationsdatum:
16. März 2010 (online)

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Abstract

A novel, one-pot approach to functionalized spirocyclic oxindoles has been developed by using vinyl malononitriles and isatin derivatives via vinylogous aldol reaction in aqueous media catalyzed by triethylamine.

Key words

isatin - vinyl malononitrile - vinylogous aldol condensation - one-pot tandem reaction - spirocyclic oxindoles

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General Procedure for the Synthesis of Spiro-Oxindole 3c: To a stirred solution of vinyl malononitrile 2a (1 mmol) and Et3N (1 mmol) in H2O-EtOH (1:1; 10 mL) at r.t., was added isatin 1c (1 mmol) and stirring was continued for about 25 min. After the reaction was complete as indicated by TLC, the solvent mixture was evaporated under vacuo. The crude product, on chromatographic purification over silica gel (Merck; 100-200 mesh; EtOAc-hexane, 3:7), yielded the desired spiro-oxindole in 87% as a single diastereomer.
Spectral Data of Spiro-Oxindole 3c (Table 2, entry 3): Yield: 87%; off-white solid; mp 196 ˚C. ¹H NMR (500 MHz, DMSO-d 6): δ = 0.37 (q, J = 13 Hz, 1 H), 1.37 (m, 2 H), 1.57 (m, 1 H), 1.88 (m, 1 H), 2.04 (m, 1 H), 2.83 (d, J = 9.9 Hz, 1 H), 4.32 (ABq, J = 16.8 Hz, 2 H), 5.16 (t, J = 9.15 Hz, 2 H), 5.46 (s, 1 H), 5.80 (m, 1 H), 7.03 (s, 2 H, D2O exchangeable), 7.06 (d, J = 7.65 Hz, 1 H), 7.09 (d, J = 7.65 Hz, 1 H), 7.13 (d, J = 7.65 Hz, 1 H), 7.37 (t, J = 7.65 Hz, 1 H). ¹³C NMR (125 MHz, DMSO-d 6): δ = 21.3, 22.9, 24.7, 38.1, 42.3, 60.9, 81.9, 110.4, 114.5, 117.9, 118.7, 123.9, 125.1, 125.3, 125.5, 131.3, 131.7, 143.3, 162.1, 171.2. IR (KBr): 3403, 3311, 3242, 3198, 2195, 1706, 1636, 1422, 1377, 763 cm-¹. MS (ESI): m/z = 334 [M + 1]. Anal. Calcd for C20H19N3O2: C, 72.05; H, 5.74; N, 12.60. Found: C, 71.09; H, 5.61; N, 12.53.

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Crystallographic data for compound 3d in this paper have been deposited with the Cambridge Crystallographic Data centre as supplemental publication No. CCDC 761167. Copies of the data can be obtained, free of charge on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [fax: +44 (1223)336033 or email: deposit@ccdc.cam.ac.uk]

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Spectral Data of Compound 6 (Table 2, entry 17): Yield: 75%; yellow solid; mp 192 ˚C. ¹H NMR (500 MHz, DMSO-d 6): δ = 0.15 (q, J = 12.2 Hz, 1 H), 1.11 (m, 1 H), 1.35 (m, 2 H), 1.81 (m, 1 H), 1.98 (m, 1 H), 2.95 (s, 1 H), 5.48 (s, 1 H), 6.97 (s, 2 H, D2O exchangeable), 7.45 (d, J = 6.9 Hz, 1 H), 7.72 (t, J = 7.65 Hz, 1 H), 7.85 (t, J = 7.65 Hz, 1 H), 8.05 (dd, J = 6.9, 8.4 Hz, 2 H), 8.33 (d, J = 8.4 Hz, 1 H). ¹³C NMR (125 MHz, DMSO-d 6): δ = 21.3, 23.2, 24.6, 38.0, 61.0, 85.2, 114.3, 119.0, 122.5, 123.3, 126.2, 127.3, 129.5, 129.8, 130.3, 130.7, 133.8, 134.5, 142.5, 162.9, 198.3. IR (KBr): 3421, 3322, 3194, 2927, 2193, 1713, 1632, 1581, 1010, 783 cm-¹. MS (ESI): m/z = 329 [M + 1]. Anal. Calcd for C20H19N3O2: C, 72.05; H, 5.74; N, 12.60. Found: C, 71.09; H, 5.61; N, 12.53.