Cycloaddition of carbonyl ylides to isatins: Synthesis of novel spiro oxindoles

Article abstract of DOI:10.1055/s-2001-10764

Facile dipolar cycloaddition reactions of isatins with carbonyl ylides, generated by Rh₂(OAc)₄ catalyzed reaction of α-diazo ketones yielding novel spiro oxindole derivatives are described.

Full text of DOI:10.1055/s-2001-10764

272
LETTER
Cycloaddition of Carbonyl Ylides to Isatins: Synthesis of Novel Spiro
Oxindoles
Vijay Nair,*a K. C. Sheela,a D. Sethumadhavan,a S. Bindu,a Nigam P. Rath,b Günter K. Eigendorfc
a Organic Chemistry Division, Regional Research Laboratory [CSIR], Trivandrum-19, India
b Department of Chemistry, The University of Missouri-St. Louis, Missouri 63121-4499, USA
c Department of Chemistry, The University of British Columbia, Vancouver V6T1Z1, Canada
Fax +91-471-491712; E-mail: gvn@csrrltrd.ren.nic.in
Received 13 December 2000
Abstract: Facile dipolar cycloaddition reactions of isatins with car-
bonyl ylides, generated by Rh2(OAc)4 catalyzed reaction of -diazo
ketones yielding novel spiro oxindole derivatives are described.
Key words: dipolar cycloaddition, carbonyl ylides, diones, spiro
oxindoles
The cycloadditions of o-quinones have invoked consider-
able interest.1-3 Very recently, we have reported that ni-
trile-N-oxides,4 carbonyl ylides,5 azomethine ylides,6,7
and betaines8,9 undergo facile dipolar cycloadditions to o-
quinones, with the latter participating as carbonyl dipo-
larophiles. In this context, we were intrigued by the possi-
bility of a novel spiro oxindole synthesis by the reaction
of carbonyl ylides with isatin. It may be mentioned that in
spite of extensive investigations on carbonyl ylides by
Figure X-ray crystal structure of 4a
Padwa,10,11 their reaction with carbonyl compounds, espe- The experiments were repeated with various isatins and
cially 1,2-diones, has received very little attention. The also diazo ketones. It was found that in all cases, the reac-
only report on the reaction of carbonyl ylide with a 1,2-di- tion proceeds smoothly to afford the spiro oxindole deriv-
one involves our own recent studies.5 The reaction of car- atives 4(b-j) in good yield. As anticipated, the ylide reacts
bonyl ylides with isatins has not been reported previously.
exclusively with the more electrophilic carbonyl and only
the endo adduct was formed in all the cases. The results
are summarized in Table 1.
Our studies were initiated with the Rh(II) acetate cata-
lyzed reaction of 1-diazo-5-phenyl-2,5-pentanedione 1a
with 1-phenylisatin 3a. This reaction proceeded smoothly
to afford a colorless crystalline product 4a in 75% yield
(Scheme 1).
Table 1
Scheme 1
a Yield based on recovered isatin.
The product was purified by silica gel column chromatog-
raphy and characterized by spectral analysis. Finally, the
structure assigned was confirmed unequivocally by single
crystal X-ray determination of 4a (Figure).
Subsequently, the reaction of the dipole generated by the
Rh(II) acetate catalyzed reaction of cyclopropyl substitut-
ed diazo ketone 512 with various isatins was performed
Synlett 2001, No. 2, 272–274 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Cycloaddition of Carbonyl Ylides to Isatins
273
(Scheme 2). In this case the reaction proceeded also very
well to afford cyclopropyl substituted spirooxindoles. The
results are summarized in Table 2.
Acknowledgement
The authors thank Dr. G. Anilkumar, The University of Nijmegen,
The Netherlands, for elemental analyses. KCS, DS and SB thank the
CSIR, New Delhi for the award of Research Fellowships.
References and Notes
(1) For earlier work on Diels-Alder reactions of o-quinones, see
Patai, S.; Rappoport, Z. In The Chemistry of Quinonoid
Compounds, Vol. 2, John Wiley & Sons: New York, 1998.
(2) (a) Nair, V.; Kumar, S. Synlett 1996, 1143 and references
cited therein. (b) Nair, V.; Kumar, S.; Rath, N. P.; Morton, G.
O. Chem. Lett. 1995, 383. (c) Nair, V.; Kumar, S.; Anilkumar,
G.; Nair, J. S. Tetrahedron 1995, 51, 9155. (d) Nair, V.;
Kumar, S.; J. Chem. Soc., Perkin Trans. 1 1996, 443. (e) Nair,
V.; Kumar, S. Synth. Commun. 1996, 26, 217.
(3) (a) Padwa, A. 1,3-Dipolar Cycloaddition Chemistry, Wiley
Interscience: New York, 1984. (b) Friedrichsen, W.; Schröer,
W. D.; Debaerdeuaeter, T. Liebigs Ann. Chem. 1980, 1850.
(c) Friedrichsen, W.; Kappe, T.; Bottcher, A. Heterocycles
1982, 19, 1083. (d) Awad, W. I.; Omran, S. M. A. R.; Sobhy,
M. J. Org. Chem. 1966, 31, 331.
Scheme 2
Table 2
(4) Nair, V.; Radhakrishnan, K. V.; Sheela, K. C.; Rath, N. P.
Tetrahedron 1999, 55, 14199.
(5) Nair, V.; Sheela, K. C.; Radhakrishnan, K.V.; Rath, N. P.
Tetrahedron Lett. 1998, 39, 5627.
(6) Nair, V.; Sheela, K.C.; Rath, N.P.; Eigendorf, G.K.
Tetrahedron Lett. 2000, 41, 6217.
(7) Nair, V.; Sheela, K.C.; Rath, N.P. Chem. Lett. 2000, 980.
(8) Nair, V.; Nair, J. S.; Vinod, A. U. Synthesis 2000, 1713.
(9) Nair, V.; Vinod, A. U.; Nair, J. S.; Sreekanth,A. R.; Rath, N.
P. Tetrahedron Lett. 2000, 41, 6675.
(10) Padwa, A.; Fryxell, G. E.; Zhi, L. J. Am. Chem. Soc. 1990,
112, 3100.
The structure of the products were assigned on the basis
of spectral data and elemental analysis or HRMS.13
Following this, the reaction of a seven membered carbon-
yl ylide generated by the Rh(II) catalyzed reaction of 1-di-
azo-6-phenyl-2,6-hexadione 8, was also performed with
N-methyl isatin. This reaction afforded a cycloadduct 9 in
32% yield along with 10 (8%) resulting from the Büchner
reaction of benzene and the carbenoid (Scheme 3).
(11) Padwa, A.; Weingarten, M. D. Chem. Rev. 1996, 96, 223.
(12) (a) Padwa, A.; Chinn, R. L.; Hornbuckle, S. F.; Zhang, Z. J. J.
Org. Chem. 1991, 56, 3271. (b) Padwa, A.; Sandanayaka, V.
P.; Curtis, E. A. J. Am. Chem. Soc. 1994, 116, 2667.
(13) Representative procedure for the synthesis of spiro
oxindoles: (1S,3’R,5S)-5-phenyl-1’-(phenyl)spiro-[6,8-
dioxabicyclo[3.2.1]octane-7,3’-[3H]indole]-2,2’(1’H)-
dione (4a): To a solution of 1-diazo-5-phenyl-2,5-
pentanedione 1a (217 mg, 1.07 mmol) in rigorously dried
toluene (3 mL),was added a catalytic amount of Rh2(OAc)4
(2 mg) and then allowed to stir at room temperature under
argon atmosphere for 1 min. To this 1-phenylisatin (200 mg,
0.89 mmol) was added and the reaction mixture was allowed
to stir for 30 minutes. The solvent was then evaporated in
vacuo. The residue obtained was chromatographed on a silica
gel column to afford 4a (298 mg, 75%) as colorless crystals.
Mp 191-193 °C; IR (KBr) max 3055, 1733, 1611, 1496, 1361,
1297, 1055, 904, 754 cm-1; 1H NMR (CDCl3-CCl4, v/v, 3:1;
300 MHz) 7.69-6.92 (m, 13H), 6.79 (d, 1H, J = 7.7 Hz), 4.63
(s, 1H), 3.40-3.32 (m, 1H), 2.75-2.48 (m, 3H); 13C NMR
(CDCl3-CCl4, v/v, 3:1; 75 MHz) 202.40, 171.04, 142.61,
139.41, 133.65, 129.64, 128.47, 128.43, 126.33, 124.94,
124.03, 111.57, 109.77, 87.61, 83.04, 35.55, 33.73. Anal.
calcd. for C25H19NO4: C, 75.48; H, 4.78; N, 3.52. Found: C,
75.29; H, 4.69; N, 3.57.
Scheme 3
In conclusion, it has been shown that the five, six, and sev-
en membered cyclic carbonyl ylides undergo facile cy-
cloaddition to isatins, thus offering an efficient and direct
method for the synthesis of novel spiro oxindole deriva-
tives. It is anticipated that the products of the cycloaddi-
tion themselves will undergo some interesting and
potentially useful transformations. Further work is in
progress.
X-ray crystal data of 4a: C25H19NO4, M. 397.41,
orthorhombic, space group Pbca, unit cell dimensions
a = 18.0300(4) A°, b = 9.8921(2) A°, c = 21.5710(6) A°,
=
= = 90°, R indices (all data) R1 = 0.1068,
wR2 = 0.1077, volume = 3847.29(16) A°3, Z = 8, D
calcd. = 1.372 Mg/m3, absorption coefficient = 0.093 mm-1,
T = 213(2) K, = 0.71073 A°, 36868 reflections measured,
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V. Nair et al.
LETTER
204.79, 171.99, 143.19, 130.47, 128.00, 124.65, 123.36,
113.67, 108.32, 86.97, 80.32, 39.46, 29.32, 26.45, 15.19,
13.48. HRMS cacld. for C16H15NO4: 285.1001. Found:
285.0989.
3648 unique [R(int) = 0.11] which were used in all calculations
(Sheldrick, G. M., Siemens, Analytical X-ray Division,
Madison, WI, 1995).
Spectral data of 7: Colorless solid, mp 158-160 °C. IR (KBr)
max 3007, 1730, 1684, 1611, 1475, 1147, 988 cm-1. 1H NMR
(CDCl3-CCl4, v/v, 3:1; 300 MHz)
J = 7.7 Hz), 4.58 (s, 1H), 3.33 (s, 3H), 3.17 (s, 3H),
1.29-1.11 (m, 4H). 13C NMR (CDCl3-CCl4, v/v, 3:1; 75 MHz)
m
d
Article Identifier:
1437-2096,E;2001,0,02,0272,0274,ftx,en;L09400ST.pdf
Synlett 2001, No. 2, 272–274 ISSN 0936-5214 © Thieme Stuttgart · New York