Indium trichloride: A useful catalyst for ionic Diels-Alder reactions

Article abstract of DOI:10.1016/S0040-4039(00)01857-8

Indium trichloride (20 mol%) in nitromethane permits ionic Diels-Alder reaction of a variety of 2,3-olefinic acetals to form the corresponding cycloadducts in good yields with good endo selectivities. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)01857-8

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 10333–10336
Indium trichloride: a useful catalyst for ionic Diels–Alder
reactions†
B. Gopal Reddy, R. Kumareswaran and Y. D. Vankar*
Department of Chemistry, Indian Institute of Technology, Kanpur 208 016, India
Received 31 August 2000; revised 12 October 2000; accepted 19 October 2000
Abstract
Indium trichloride (20 mol%) in nitromethane permits ionic Diels–Alder reaction of a variety of
2,3-olefinic acetals to form the corresponding cycloadducts in good yields with good endo selectivities.
© 2000 Elsevier Science Ltd. All rights reserved.
Keywords: ionic Diels–Alder reaction; indium trichloride; asymmetric catalysis.
The ionic Diels–Alder (IDA) reaction,2 using a 2,3-olefinic acetal instead of an a,b-unsatu-
rated carbonyl compound as a dienophile, is a useful variation of the conventional Diels–Alder
reaction in cases where Lewis acids cause polymerization of dienophiles or thermal means do
not readily lead to the expected adducts. Gassman and co-workers3 systematically studied this
reaction and several new aspects were reported by them in a series of excellent papers.
Additionally, Grieco et al.4 have reported that LiClO4·Et2O (4 M or 5 M solution) along with
1% camphorsulfonic acid permits the ionic Diels–Alder reaction. In this study an important
observation that addition of 1% camphorsulfonic acid is necessary, otherwise LiClO4·Et2O does
not give any desired adduct, deserves special mention. We have also reported5 that LiClO4 in
nitromethane (4 M solution), without the addition of camphorsulfonic acid, leads to the desired
ionic Diels–Alder adducts from a variety of olefinic acetals. This change in the dipole moment
of 1.33 D of diethyl ether to 3.4 D of nitromethane was attributed as the possible cause of the
success of the reaction using LiClO4–CH3NO2 since ionic Diels–Alder reactions involve charged
intermediate species. In addition to this, we also reported that Nafion-H5 acts as an excellent
solid catalyst for the ionic Diels–Alder reaction and in some cases with improved selectivity.
Apart from this there have been efforts6,7 to study the asymmetric variance of IDA reactions
in the literature. Our endeavors5 in this direction involved utilization of chiral acetals containing
* Corresponding author. Tel: +0091 512 597 169; fax: 0091 512 590 007; e-mail: vankar@iitk.ac.in
† Part 14, General Synthetic Methods. For part 13 see: Ref. 1.
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)01857-8

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dienophiles with a side chain appendage using TiCl4, BF3·Et2O and TiCl2(iPrO)2 as catalysts. On
the other hand, our efforts to study8 these reactions with achiral olefinic acetals in the presence
of chiral catalysts have met with little success. Thus, reaction of olefinic acetal 1 (Scheme 1) with
cyclopentadiene in the presence of chiral catalyst 2,9 derived from TADDOL, gave the expected
IDA adduct 3 in 71% yield. This was then hydrolyzed to the known aldehyde 4 which, however,
had rather low enantioselectivity (10.4% ee)10 possibly because of the flexible transition state 5
as a result of very high reactivity of the catalyst 2, even at low temperatures (−78 to −45°C).
In order to perform asymmetric IDA reactions, it would thus be desirable to use a catalyst
which is moderately reactive so that it permits transition states of type 5 to remain rather close
to cause diastereomeric differentiation. Clearly, such catalysts should also be capable of
interacting with chiral ligands and yet bear sufficient reactivity towards IDA reactions. Towards
this effect, we considered InCl3,11–16 Yb(OTf)317 and Sc(OTf)317 as catalysts which have, in recent
years, gained importance owing to their Lewis acidic character and which could also be
maintained in aqueous medium. As a result of this property, several reactions such as
Diels–Alder,12,17 hetero Diels–Alder,13 aldol,14 Friedel–Crafts15 and Ferrier reactions,16 with
some advantages over the traditional Lewis acids have appeared in the literature. Additionally,
use of chiral ligands such as TADDOL and (R)- or (S)-BINOL to modify Yb(OTf)3 and
Sc(OTf)3 to effect asymmetric induction has enjoyed some success.17 To the best of our
knowledge, no report is known where InCl3, Yb(OTf)3 or Sc(OTf)3 have been employed in IDA
reactions. This aspect, coupled with the fact that an appropriate bidentate ligand could modify17
each of these into a chiral catalyst, led us to examine their behavior in IDA reactions.
Scheme 1.
Indeed InCl3 was found to be an excellent catalyst in IDA reactions but surprisingly, however,
with neither Yb(OTf)3 nor Sc(OTf)3 were IDA reactions clean and no cycloadduct was formed
indicating thereby that InCl3 is indeed a unique catalyst for these reactions. A variety of acyclic
and cyclic olefinic acetals undergo reactions with isoprene and cyclopentadiene in the presence
of 20 mol% of InCl3 to form the corresponding cycloadducts in good yields (Table 1). Among
the various solvents nitromethane was found to be the best in terms of reaction time and yield,
indicating once again that the transition state does impart some ionic character. In the case of
cyclopentadiene based reactions, the endo/exo ratio was fairly good and comparable to the
4,5
LiClO4 and Nafion-H5 based reactions. All the cycloadducts were hydrolyzed to the corre-
sponding carbonyl compounds and their spectral data compared with the literature5 values.

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Table 1
Ionic Diels–Alder reaction using InCl3
For the asymmetric variation, InCl3 was then treated with TADDOL and (R)-BINOL
separately in the presence of NaH (or Et3N) in THF to form catalysts 6 and 7 (Scheme 1),
respectively, and further reacted in situ with 1 and cyclopentadiene in nitromethane. Unfortu-
nately, however, no IDA reaction was found to occur, perhaps indicating that the modified

10336
indium catalysts are not sufficiently electrophilic to permit opening of the olefinic acetals for
ionic Diels–Alder reactions.
Nevertheless, the success of indium chloride as a catalyst for achiral IDA reactions is
important and this suggests that other more reactive derivatives of indium such as indium
triflate based chiral catalysts may be useful for asymmetric IDA reactions. Work towards this
end is in progress.
General experimental procedure: To a stirred solution of a dienophile (2 mmol) and freshly
distilled diene (6 mmol) (isoprene or cyclopentadiene) in nitromethane (4 mL) was added
anhydrous InCl3 (20 mol%) (10 mg hydroquinone was also added while using isoprene) at
15–20°C. The progress of the reaction was monitored by TLC and after completion the reaction
mixture was extracted with CH2Cl2 (3×20 mL), washed with water, brine and dried over
anhydrous Na2SO4. Evaporation of the solvent and purification by column chromatography
gave the desired cycloadducts.
Acknowledgements
We thank the Department of Science and Technology and Council of Scientific and Industrial
Research, New Delhi for financial support.
References
1. Kumareswaran, R.; Pachamuthu, K.; Vankar, Y. D. Synlett 2000, 1652.
2. (a) Gassman, P. G.; Singleton, D. A.; Wilwerding, J. J.; Chavan, S. P. J. Am. Chem. Soc. 1987, 109, 2182. (b)
Pascal-Teresa, B. D.; Houk, K. N. Tetrahedron Lett. 1996, 37, 1759. (c) For a short review, see: Sanghi, R.;
Vankar, P. S.; Vankar, Y. D. J. Ind. Chem. Soc. 1998, 75, 709.
3. Gassman, P. G.; Chavan, S. P. Tetrahedron Lett. 1990, 31, 6489.
4. Grieco, P. A.; Colins, J. L.; Handy, S. T. Synlett 1995, 1155.
5. Kumareswaran, R.; Vankar, P. S.; Reddy, M. V. R.; Pitre, S. V.; Roy, R.; Vankar, Y. D. Tetrahedron 1999, 55,
1099.
6. Alexakis, A.; Mangeney, P. Tetrahedron: Asymmetry 1990, 1, 477.
7. Sammakia, T.; Berliner, M. A. J. Org. Chem. 1994, 59, 6890.
8. Kumareswaran, R. PhD dissertation, IIT Kanpur, 1998.
9. Seebach, D.; Dahinden, R.; Marti, R. E.; Beck, A. E.; Plattner, D. A.; Kuhnle, N. M. J. Org. Chem. 1995, 60,
1788.
10. The rotation value of [h]2D5=+14 (c 1, CH2Cl2) was observed for the aldehyde 4 and the ee was calculated by
comparing the rotation value with the literature value, cf. Ishihara, K.; Kurihara, H.; Yamamoto, H. J. Am.
Chem. Soc. 1996, 118, 3049.
11. Babu, G.; Perumal, P. T. Aldrichim. Acta 2000, 33, 16.
12. Loh, T.-P.; Pei, J.; Lin, M. Chem. Commun. 1996, 2315.
13. Babu, G.; Perumal, P. T. Tetrahedron 1999, 55, 4793.
14. Loh, T.-P.; Pei, J.; Cao, G.-Q. Chem. Commun. 1996, 1819.
15. Miyai, T.; Onsihi, Y.; Baba, A. Tetrahedron 1999, 55, 1017.
16. Babu, B. S.; Balasubramanian, K. K. Tetrahedron Lett. 2000, 41, 1271.
17. (a) Kobayashi, S.; Hachiya, I.; Takahori, T.; Araki, M.; Ishitani, H. Tetrahedron Lett. 1992, 33, 6815. (b)
Arseniyadis, S.; Rodriguez, R.; Yashunsky, D. V.; Camara, J.; Ourisson, G. Tetrahedron Lett. 1994, 35, 4843. (c)
Kobayashi, S. Synlett 1994, 689. (d) Kobayashi, S.; Ishitani, H.; Araki, M.; Hachiya, I. Tetrahedron Lett. 1994,
35, 6325.
.