ORGANIC
LETTERS
2012
Vol. 14, No. 11
2762–2765
Asymmetric Pericyclic Cascade Approach
to Spirocyclic Oxindoles
ꢀꢁ ꢀ
Edward Richmond, Nicolas Duguet, Alexandra M. Z. Slawin, Tomas Lebl, and
Andrew D. Smith*
EaStCHEM, School of Chemistry, University of St. Andrews, North Haugh,
St. Andrews, KY16 9ST, U.K.
Received April 16, 2012
ABSTRACT
The reaction of chiral N-arylnitrones with carbocyclic alkylarylketenes generates spirocyclic oxindoles in good yields and with excellent levels of
enantioselectivity (90ꢀ99% ee) via a pericyclic cascade process.
Spirocyclic oxindoles are an important structural motif
central to a variety of both natural products1 and phar-
maceutically relevant materials.2 Synthetic routes to 3,3-
disubstituted oxindoles bearing a spiro-heterocyclic frame-
work (such as 3,30-pyrrolidines) are relatively common.3
However, routes that access 3,3-spirocarbocyclic oxi-
ndoles, especially asymmetric strategies, are relatively
less explored, with the alkaloid natural product gelsemine
providing a major impetus for synthetic exploration.4
Prominent examples of approaches toward spirocarbocyc-
lic oxindoles include Lewis acid mediated cyclizations,5
adaptations of classic Fischer indole chemistry and other
[3,3]-sigmatropic rearrangements,6 radical cyclizations,7
catalytic asymmetric domino/tandem processes,8 as well
as transition-metal- and organo-catalyzed asymmetric
cycloadditions,9 among others.10 Overman’s extensive
(5) (a) England, D. B.; Merey, G.; Padwa, A. Org. Lett. 2007, 9, 3805–
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Atarashi, S.; Choi, J.-K.; Hart, D. J. J. Am. Chem. Soc. 1994, 116, 6943–
6944. (b) Dutton, K. J.; Steel, R. W.; Tasker, A. S.; Popsavin, V.;
Johnson, A. P. J. Chem. Soc., Chem. Commun. 1994, 765–766.
(8) (a) Miyamoto, H.; Okawa, Y.; Nakazaki, A; Kobayashi, S.
Angew. Chem., Int. Ed. 2006, 45, 2274–2277. (b) Bencivenni, G.; Wu,
L.-Y.; Mazzanti, A.; Giannichi, B.; Pesciaioli, F.; Song, M.-P.; Bartoli,
G.; Melchiorre, P. Angew. Chem., Int. Ed. 2009, 48, 7200–7203. (c) Jiang,
K.; Jia, Z.-J.; Chen, S.; Wu, L.; Chen, Y.-C. Chem.;Eur. J. 2010, 16,
2852–2856. (d) Lan, Y.-B.; Zhao, H.; Liu, Z.-M.; Liu, G.-G.; Tao, J.-C.;
Wang, X.-W. Org. Lett. 2011, 13, 4866–4869. (e) Wang, L.-L.; Peng, L.;
Bai, J. F.; Jia, L. N.; Luo, X.-Y.; Huang, Q.-C.; Xu, X.-Y.; Wang, L.-X.
Chem. Commun. 2011, 47, 5593–5595.
(9) (a) Trost, B. M.; Cramer, N.; Silverman, S. M. J. Am. Chem. Soc.
2007, 129, 12396–12397. (b) Wei, Q.; Gong, L.-Z. Org. Lett. 2010, 12,
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Chem. Soc. 2011, 133, 12354–12357.
(10) (a) Wenkert, E.; Liu, S. Synthesis 1992, 323. (b) Feldman, K. S.;
Karatjas, A. G. Org. Lett. 2006, 8, 4137–4140. (c) Pettersson, M.;
Knueppel, D.; Martin, S. F. Org. Lett. 2007, 9, 4623–4626. (d) Richter,
J. M.; Ishihara, Y.; Masuda, T.; Whitefield, B. W.; Llamas, T.; Pohjakallio,
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(1) For a review, see: (a) Marti, C.; Carreira, E. M. Eur. J. Org.
Chem. 2003, 2209–2219. For selected papers, see: (b) Fischer, C.;
Meyers, C.; Carreira, E. M. Helv. Chim. Acta 2000, 83, 1175–1181. (c)
Lerchner, A.; Carreira, E. M. J. Am. Chem. Soc. 2002, 124, 14826–
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694–696.
(2) (a) Beccalli, E. M.; Clerici, F.; Gelmi, M. L. Tetrahedron 2003, 59,
4615–4622. (b) Antonchick, A. P.; Gerding-Reimers, C.; Catarinella,
M.; Schuermann, M.; Preut, H.; Ziegler, S.; Rauh, D.; Waldmann, H.
Nature Chem. 2010, 2, 735–740.
(3) For a review, see: (a) Galliford, C. V.; Scheidt, K. A. Angew.
Chem., Int. Ed. 2007, 46, 8748–8758. For select recent strategies, see: (b)
Lakshmaiah, G.; Kawabata, T.; Shang, M.; Fuji, K. J. Org. Chem. 1999,
64, 1699–1704. (c) Kumar, U. K. S.; Ila, H.; Junjappa, H. Org. Lett.
2001, 3, 4193–4196. (d) Cravotto, G.; Giovenzana, G. B.; Pilati, T.; Sisti,
M.; Palmisano, G. J. Org. Chem. 2001, 66, 8447–8453. (e) Trost, B. M.;
Brennan, M. K. Org. Lett. 2006, 8, 2027–2030. (f) Castaldi, M. P.;
Troast, D. M.; Porco, J. A., Jr. Org. Lett. 2009, 11, 3362–3365. (g)
Zhang, Y.; Panek, J. S. Org. Lett. 2009, 11, 3366–3369. (h) Cao, Y.;
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(4) For a review of strategies toward syntheses of gelsemine, see: Lin, H.;
Danishefsky, S. J. Angew. Chem., Int. Ed. 2003, 42, 36–51.
r
10.1021/ol300982f
Published on Web 05/14/2012
2012 American Chemical Society