ORGANIC
LETTERS
2
007
Vol. 9, No. 1
7-60
Simple and One-Pot Protocol for
Synthesis of Indene-spiro-oxindoles
Involving Tandem Prins and
5
Friedel−Crafts Reactions
Deevi Basavaiah* and Kanumuri Ramesh Reddy
School of Chemistry, UniVersity of Hyderabad, Hyderabad-500 046, India
Received October 17, 2006
ABSTRACT
A simple and one-pot protocol for the synthesis of indene-spiro-oxindole derivatives via TiCl
4
-mediated reaction between 1,1-diarylethylenes
and isatin derivatives involving construction of two carbon−carbon bonds through tandem Prins and intramolecular Friedel−Crafts (PFC)
reactions has been described. A plausible mechanism for this transformation is also presented.
1
Indene and spiro-indene derivatives occupy a special place
in organic and medicinal chemistry because these compounds
are well-known h5-HT6 serotonin receptors, estrogen recep-
tor modulators, antiproliferative agents, and oxytocin an-
nected by an interesting spiro-bridge would be of biological
interest and also aesthetically appealing and in continuation
of our interest in the synthesis of heterocyclic molecules,3
we herein report a facile reaction of 1,1-diarylethylenes with
2
tagonists. The spiro-oxindole framework represents yet
isatin derivatives under the influence of TiCl to provide a
4
another important structural organization present in a number
of bioactive natural products such as coerulescine, horsfiline,
welwitindolinone A, spirotryprostatin A, elacomine, alsto-
nisine, surugatoxin, etc. With the view that the molecules
containing both the indene and oxindole frameworks con-
novel one-pot protocol for the synthesis of 1H-indene-spiro-
oxindole derivatives via the construction of two C-C bonds
4
in an operationally simple process involving tandem Prins
5
and intramolecular Friedel-Crafts reactions (PFC reaction
sequence). We have been working for the last several years
3
b-d
on various aspects of the Baylis-Hillman reaction,
which
is a popular, atom-economical, C-C bond forming reaction.6
On the basis of our studies on the application of isatin
derivatives as electrophiles in the Baylis-Hillman reaction7
(
1) (a) Kolanos, R.; Siripurapu, U.; Pullagurla, M.; Riaz, M.; Setola, V.;
Roth, B. L.; Dukat, M.; Glennon, R. A. Bioorg. Med. Chem. Lett. 2005,
5, 1987-1991. (b) Watanabe, N.; Nakagava, H.; Ikeno, A.; Minato, H.;
Kohayakawa, C.; Tsuji, J. Bioorg. Med. Chem. Lett. 2003, 13, 4317-4320.
c) Karaguni, I.-M.; Glusenkamp, K.-H.; Langerak, A.; Geisen, C.; Ullrich,
V.; Winde, G.; Moroy, T.; Muller, O. Bioorg. Med. Chem. Lett. 2002, 12,
1
(
7
09-713. (d) Evans, B. E.; Leighton, J. L.; Rittle, K. E.; Gilbert, K. F.;
(3) (a) Basavaiah, D.; Rao, J. S.; Reddy, R. J.; Rao, A. J. Chem. Commun.
2005, 2621-2623. (b) Basavaiah, D.; Satyanarayana, T. Chem. Commun.
2004, 32-33. (c) Basavaiah, D.; Rao, A. J. Chem. Commun. 2003, 604-
605. (d) Basavaiah, D.; Satyanarayana, T. Org. Lett. 2001, 3, 3619-3622.
(4) For a leading review on the Prins reaction, see: Adams, D. R.;
Bhatnagar, S. P. Synthesis 1977, 661-672.
(5) For a leading reference on the Friedel-Crafts reaction, see: (a) Olah,
G. A.; Krishnamurti, R.; Prakash, G. K. S. In ComprehensiVe Organic
Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon: New York, 1991;
Vol. 3, pp 293-339.
Lundell, G. F.; Gould, N. P.; Hobbs, D. W.; Dipardo, R. M.; Veber, D. F.;
Pettibone, D. J.; Clineschmidt, B. V.; Anderson, P. S.; Freidinger, R. M. J.
Med. Chem. 1992, 35, 3919-3927.
(2) (a) Chang, M.-Y.; Pai, C.-L.; Kung, Y.-H. Tetrahedron Lett. 2005,
4
6, 8463-8465. (b) Baran, S. P.; Richter, R. M. J. Am. Chem. Soc. 2005,
1
27, 15394-15396. (c) Hilton, S. T.; Ho, T. C. T.; Pljevaljcic, G.; Jones,
K. Org. Lett. 2000, 2, 2639-2641. (d) Kosuge, T.; Tsuji, K.; Hirai, K.;
Yamaguchi, K.; Okamoto, T.; Iitaka, Y. Tetrahedron Lett. 1981, 22, 3417-
3
420.
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0.1021/ol062561m CCC: $37.00
© 2007 American Chemical Society
Published on Web 12/07/2006