8175
of the cyclopropyl precursor 7a gave <5% of the desired spirocyclic product 9a, and gave almost
exclusively the dihydroindole 8 arising from direct cyclisation of the aryl radical onto the allyl
bond. Presumably, this outcome is the result of the greater bond strength of a cyclopropyl
carbonꢀhydrogen bond compared with the carbonꢀhydrogen bond strengths in the other
substrates, which makes [1,5]-hydrogen atom abstraction less efficient.
In order to complete the synthesis of the spirocyclic pyrrolidin-2-one systems, oxidative
removal of the p-methoxyphenyl protecting group was investigated. This proved straightforward
and was achieved by treatment of a solution of the spirocyclic pyrrolidin-2-one in acetonitrile
with an aqueous solution of ceric ammonium nitrate10 to give the spirocyclic lactams 10a–d in
good yield (Scheme 3).
Scheme 3.
In summary, an aryl radical has been used to generate an alkyl radical at an unfunctionalised
site. The cyclisation of this alkyl radical onto an appropriately situated carbonꢀcarbon double
bond gives spirocyclic pyrrolidin-2-ones from which the N-aryl group can be removed. This
tandem [1,5]-hydrogen atom abstraction/cyclisation protocol is both short and high yielding.
References
1. (a) Montevecchi, P. C.; Navacchia, M. L. Tetrahedron Lett. 1996, 37, 6583–6586. (b) Barclay, L. R. C.; Griller,
D.; Ingold, K. U. J. Am. Chem. Soc. 1974, 96, 3011–3012. (c) Brunton, G.; Griller, D.; Barclay, L. R. C.; Ingold,
K. U. J. Am. Chem. Soc. 1976, 98, 6803–6811.
2. (a) Fiumana, A.; Jones, K. Tetrahedron Lett. 2000, 41, 4209–4211; (b) Chatgilialoglu, C.; Gimisis, T.; Spada, G.
P. Chem. Eur. J. 1999, 5, 2866–2876. (c) Alcaide, B.; Rodriguez-Campos, I. M.; Rodriguez-Lopez, J.; Rodriguez-
Vincente, A. J. Org. Chem. 1999, 64, 5377–5387. (d) Curran, D. P.; Xu, J. J. Am. Chem. Soc. 1996, 118,
3142–3147. (e) Williams, L.; Booth, S. E.; Undhaim, K. Tetrahedron 1994, 50, 13697–13708. (f) Curran, D. P.;
Liu, H. J. Chem. Soc., Perkin Trans. 1 1994, 1377–1393.
3. (a) Yamazaki, N.; Eichenberger, E.; Curran, D. P. Tetrahedron Lett. 1994, 35, 6623–6626. (b) Curran, D. P.;
Shen, W. J. Am. Chem. Soc. 1993, 115, 6051–6059. (c) Denenmark, D.; Winkler, T.; Waldner, A.; De Mesmaeker,
A. Tetrahedron Lett. 1992, 33, 3613–3616. (d) Curran, D. P.; Somayajula, K. U.; Yu, H. Tetrahedron Lett. 1992,
33, 2295–298. (e) Beckwith, A. L. J.; Boate, D. R. J. Org. Chem. 1988, 53, 4339–4348.
4. Beckwith, A. L. J.; Storey, J. M. D. J. Chem. Soc., Chem. Commun. 1995, 977–978.
5. Jones, K.; Storey, J. M. D. J. Chem. Soc., Chem. Commun. 1992, 1766–1767.
6. (a) Reddy, P. A.; Hsiang, B. C. H.; Latifi, T. N.; Hill, W. M.; Woodward, K. E.; Rothman, S. M.; Ferrendelli,
J. A.; Covey, D. F. J. Med. Chem. 1996, 39, 1898–1906. (b) Kimura, Y.; Atarashi, S.; Kawakami, K.; Sato, K.;
Hayakawa, I. J. Med. Chem. 1994, 37, 3344–3352.
7. (a) Smolanoff, J.; Kluge, A. F.; Meinwald, J.; McPhail, A.; Miller, R. W.; Hicks, H.; Eisner, T. Science 1975, 188,
734–736. (b) Ruangrungsi, N.; Likhitwitayawuid, K.; Jongbunprasert, V.; Ponglux, J.; Aimi, N.; Ogata, K.;
Yasuoka, M.; Haginiwa, J.; Sakai, S. Tetrahedron Lett. 1987, 28, 3679–3682.
8. Typical experimental procedure: tributyltin hydride (379 mg, 1.30 mmol) and azoisobutyronitrile (10 mg) were
added to a solution of 7c (400 mg, 1.18 mmol) in toluene (50 ml). The reaction mixture was heated at 110°C for
two hours, cooled, poured into ether, and washed with ammonia solution (10%). The ether solution was dried