High nucleophilicity of cyclic amidocarbene toward aryl isocyanates, new approach to spiro[azetidinone-4,3′-indolinone] derivatives

Article abstract of DOI:10.1021/jo060265h

The nucleophilic addition of β-lactam-4-ylidenes 2, a type of ambiphilic cyclic amidocarbene, to aryl isocyanates has been studied and their application in organic synthesis has been demonstrated. Thermolysis of spiro[β-lactam-4,2′-oxadiazolines] 1 in the

Full text of DOI:10.1021/jo060265h

High Nucleophilicity of Cyclic Amidocarbene toward Aryl
Isocyanates, New Approach to Spiro[azetidinone-4,3′-indolinone]
Derivatives
Ying Cheng,* Bo Wang, and Lan-Qing Cheng
Chemistry Department, Beijing Normal UniVersity, Beijing 100875, China
ycheng2@bnu.edu.cn
ReceiVed February 8, 2006
The nucleophilic addition of â-lactam-4-ylidenes 2, a type of ambiphilic cyclic amidocarbene, to aryl
isocyanates has been studied and their application in organic synthesis has been demonstrated. Thermolysis
of spiro[â-lactam-4,2′-oxadiazolines] 1 in the presence of aryl isocyanates afforded both N-lactam and
O-lactam substituted spiro[azetidine-2-one-4,3′-indole-2′-one] derivatives 5 and 6 in the total yield of
65-86%. Upon hydrolysis, products 5 and 6 were converted into spiro[azetidine-2-one-4,3′-indole-2′-
one] 9 that was analogous to known biologically active compounds.
Introduction
metal complexes.3,5 In addition, the nucleophilic carbenes are
also versatile intermediates in the construction of novel multi-
functional heterocycles.6 For example, diamino-, aminooxy-,
aminothio-, dioxy-, dithio-, and oxythiocarbenes have been
reported to react with aryl or vinyl isocyanates to form N,N-
diarylimidazoline-2,4-dione (hydantoin)7 or pyrroline-2-one
derivatives,8 respectively. In comparison to nucleophilic car-
benes, the chemistry of ambiphilic carbenes has scarcely been
explored. Except for cyclopropanation of alkenes and alkynes,
ambiphilic carbenes seem not to have found much usage in
organic synthesis. In 1990s, Warkentin and co-workers inves-
Carbene is the sole two-valence intermediate in the carbon-
central active intermediates. The completion of the octet of
electrons at the carbene center is, in general, the driving force
behind the carbene reactions. Therefore, these active species
normally behave as electrophiles, and react more effectively
with electron-rich substrates than with electron-deficient ones.1
If one or two heteroatoms (e.g., O, N, or S) are directly bound
to the carbene center, the electronic delocalization of the lone
pair electrons on heteroatoms can compensate for the electronic
deficiency at the carbene and could cause the nature of the
carbene to change from electrophilic to nucleophilic.2 Carbenes
can thus be divided into electrophilic, ambiphilic, and nucleo-
philic carbenes. The nucleophilic carbenes, especially the
N-heterocyclic carbenes,3 have attracted considerable attention
in recent years because many N-heterocyclic carbenes are stable
and can be used as organocatalysts4 and as ligands in transition
(3) Herrmann, W. A.; Ko¨cher, C. Angew. Chem., Int. Ed. Engl. 1997,
36, 2162.
(4) (a) Grasa, G. A.; Kissling, R. M.; Nolan, S. P. Org. Lett. 2002, 4,
3583. (b) Grasa, G. A.; Gu¨veli, T.; Singh, R.; Nolan, S. P. J. Org. Chem.
2003, 7, 2812. (c) Nyce, G. W.; Lamboy, J. A.; Connor, E. F.; Waymouth,
R. M.; Hedrick, J. L. Org. Lett. 2002, 4, 3587. (d) Singh, R.; Kissling, R.
M.; Letellier, M.-A.; Nolan, S. P. J. Org. Chem. 2004, 69, 209. (e) Davis,
J. H., Jr.; Forrester, K. J. Tetrahedron Lett. 1999, 40, 1621. (f) Enders, D.;
Kallfass, U. Angew. Chem., Int. Ed. 2002, 41, 1743. (g) Kerr, M. S.; Read
de Alaniz, J.; Rovis, T. J. Am. Chem. Soc. 2002, 124, 10298. (h) Enders,
D.; Balensiefer, T. Acc. Chem. Res. 2004, 37, 534.
* Address correspondence to this author. Phone: +86-10-58805558. Fax:
+86-10-58802075.
(1) (a) Matlin, S. A. Ann. Rep. Prog. Chem., Sect. B: Org. Chem. 1979,
75, 79. (b) Buehler, C. A. J. Chem. Edu. 1972, 49, 239.
(2) (a) Moss, R. A. Acc. Chem. Res. 1989, 22, 15. (b) Warkentin, J.
AdV. Carbene Chem. 1998, 2, 245.
(5) Bourissou, D.; Guerret, O.; Gabbai, F. P.; Bertrand, G. Chem. ReV.
2000, 100, 39.
(6) Cheng, Y.; Meth-Cohn, O. Chem. ReV. 2004, 104, 2507.
10.1021/jo060265h CCC: $33.50 © 2006 American Chemical Society
Published on Web 05/11/2006
4418
J. Org. Chem. 2006, 71, 4418-4427

Spiro[azetidinone-4,3′-indolinone] DeriVatiVes
TABLE 1. The Optimization of Thermolysis of
Spiro[â-lactam-4,2′-oxadiazoline] 1b and Reaction between Carbene
2b and p-Chlorophenyl Isocyanate 3c
tigated the reactions of â-lactam-4-ylidenes, a type of cyclic
amidocarbenes derived from thermolysis of spiro[â-lactam-4,2′-
oxadiazolines],9 with both electron-rich and electron-deficient
alkenes or alkynes, and they demonstrated the â-lactam-4-
ylidenes to be ambiphilic carbenes but with pronounced
electrophilic activity.10 We have been interested in the chemistry
of nucleophilic and ambiphilic carbenes for some time,11 and
our previous studies have shown the reaction outcomes being
strongly influenced by the structures of both carbenes and their
reaction partners. Although the â-lactam-4-ylidenes are formally
N-heterocyclic carbenes, the amido nitrogen is relatively a weak
electronic donor and therefore they might not be distinctly
nucleophilic. With the purpose of investigating the nucleophilic
behavior of cyclic amidocarbenes, and of preparing multifunc-
tional â-lactam derivatives of pharmaceutical importance, we
undertook the current study of the reaction between â-lactam-
4-ylidenes and aryl isocyanates. Herein, we report our findings
that â-lactam-4-ylidenes, the typical ambiphilic carbenes, actu-
ally behave as good nucleophiles as bisheteroatom-substituted
carbenes in the addition reaction to isocyanates to form both
N- and O-lactam substituted spiro[azetidine-2-one-4,3′-indole-
2′-one] derivatives in the total yield of 65-86%.
yield (%)a
(°C) (h) 4b 5b 6b total
starting
entry materials 1:3
temp time
solvent
1
2
3
4
5
6
7
8
9
1b 3c 1:1 toluene
1b 3c 1:2 toluene
110
110
110
110
110
80
100
100
80
12
12
4
7
28 41 73
23 39 69
1b 3c 1:3 toluene
1b 3c 1:4 toluene
1b 3c 2:1 toluene
1b 3c 2:1 benzene
1b 3c 2:1 1,4-dioxane
1b 3c 2:1 CH3CH2CN
1b 3c 2:1 ClCH2CH2Cl
12 18 20 28 66
12 18 25 29 72
12
12
12
12
12
12
33 49 82
18 43 61
32 42 74
46 31 77
28 29 57
40 18 58
10
1b 3c 2:1 Cl2CHCH2Cl 110
a Isolated yield b Calculation of the yield of 4 was based on the reaction
of one carbene with two isocyanate molecules, while the yields of 5 and 6
were based on the reaction of two carbenes with one isocyanate molecule.
SCHEME 1. The Reactions between â-Lactam-4-ylidenes 2
and Aryl Isocyanates 3
Results and Discussion
All cyclic amidocarbenes, â-lactam-4-ylidenes 2, were gener-
ated in situ by thermolysis of spiro[â-lactam-4,2′-oxadiazolines]
1 according to the Warkentin’s method.9 Initially, we examined
the reactivity of 2b (R ) Me, X ) Me) by refluxing
oxadiazoline 1b with 1 equiv of aryl isocyanate 3c (Y ) Cl) in
toluene. The reaction proceeded smoothly to give three types
of products 4bc, 5bc, and 6bc in the total yield of 73% (entry
1 in Table 1, Scheme 1). To increase the chemical yields and
to improve the selectivity, the reaction was optimized by varying
the ratio of starting materials, reaction media, and temperature.
It was found that, in the presence of an excess amount of
isocyanate 3c, the yield of 4bc slightly increased. When the
carbene source 1b was doubled, 5bc and 6bc were isolated in
a combined yield of 82% and the formation of 4bc was
eliminated (entry 5, Table 1). Toluene, 1,4-dioxane, and benzene
were observed to favor the formation of O-substituted product
6bc, whereas propionitrile and trichloroethane were beneficial
to N-substituted product 5bc. Since products 5 and 6 were
(7) (a) Enders, D.; Breuer, K.; Runsink, J.; Teles, J. H. Liebigs Ann.
1996, 2019. (b) Katritzky, A. R.; Cheng, D.; Leeming, P.; Ghiviriga, I.;
Hartshorn, C. M.; Steel, P. J. J. Heterocycl. Chem. 1996, 33, 1935. (c)
Hoffmann, R. W.; Hagenbruch, B.; Smith, D. M. Chem. Ber. 1977, 110,
23. (d) Couture, P.; Terlouw, J. K.; Warkentin, J. J. Am. Chem. Soc. 1996,
118, 4214. (e) Couture, P.; Warkentin J. Can. J. Chem. 1997, 75, 1281. (f)
Gerninghaus, C.; Kuemmell, A.; Seitz, G. Chem. Ber. 1993, 126, 733. (g)
Haug, E.; Kantlehner, W.; Hagen, H.; Speh, P.; Braeuner, H.-J. Liebigs
Ann. Chem. 1988, 6, 605. (h) Hoffmann, R. W.; Reiffen, M. Chem. Ber.
1977, 110, 49. (i) El-Saidi, M.; Kassam, K.; Pole, D. L.; Tadey, T.;
Warkentin, J. J. Am. Chem. Soc. 1992, 114, 8751.
(8) (a) Rigby, J. H.; Wang, Z. Org. Lett. 2002, 4, 4289. (b) Rigby, J. H.;
Cavezza, A.; Ahmed, G. J. Am. Chem. Soc. 1996, 118, 12848. (c) Rigby,
J. H.; Cavezza, A.; Heeg, M. J. Tetrahedron Lett. 1999, 40, 2473. (d) Rigby,
J. H.; Laurent, S. J. Org. Chem. 1999, 64, 1766. (e) Rigby, J. H.; Laurent,
S.; Dong, W.; Danca, M. D. Tetrahedron 2000, 56, 10101.
derived respectively from two different intermediates, indoline-
2-one 9 and 2-hydroxyl indolenine 10 (vide infra), the solvent
effect on the outcomes of reaction was most probably due to
the stabilization of the intermediates 9 and 10 by a polar and
nonpolar solvent, respectively.
To examine the scope of the reaction and to have a good
understanding of the mechanism, the reactions between carbenes
2 and aryl isocyanates 3 both bearing different substituents were
investigated by refluxing the mixture of carbene sources 1 and
aryl isocyanates 3 (1:3 2:1) in toluene for 12 h. As illustrated
in Table 2, the substituents on phenyl groups in both carbene
and isocyanate have a negligible effect on the outcomes of the
reaction. In all cases, the reaction afforded moderate to good
overall yields of 5 and 6 with the ratio of 6 over 5 ranging
from 1:1 to 2:1 (Scheme 1 and Table 2).
(9) (a) Zoghbi, M.; Warkentin, J. J. Org. Chem. 1991, 56, 3214. (b)
Zoghbi, M.; Warkentin, J. Can. J. Chem. 1993, 71, 912.
(10) (a) Zoghbi, M.; Warkentin, J. Can. J. Chem. 1992, 70, 2967. (b)
Zoghbi, M.; Horne, S. E.; Warkentin, J. J. Org. Chem. 1994, 59, 4090.
(11) (a) Cheng, Y.; Zhu, Q.; Li, Q.-S.; Meth-Cohn, O. J. Org. Chem.
2005, 70, 4840. (b) Cheng, Y.; Yang, H.; Meth-Cohn, O. Chem. Commun.
2003, 90. (c) Cheng, Y.; Yang, H.; Meth-Cohn, O. Org. Biomol. Chem.
2003, 1, 3605.
Both products 5 and 6 exist as a pair of diastereoisomers.
Most of the diastereoisomers were separated successfully by
J. Org. Chem, Vol. 71, No. 12, 2006 4419

Cheng et al.
TABLE 2. The Reactions of Carbenes 2 with Aryl Isocyanates 3
under Optimal Conditions
It is worth noting that products 5 and 6 show distinctly
different 13C NMR and 1H NMR spectra and they can be used
in turn as diagnostics to differentiate 5 and 6. For example,
N,N-substituted carbon (4′′-C) of 5-I and 5-II resonated in a
range of 68-70 ppm in 13C NMR, while N,O-substituted carbon
of 6-I and 6-II appeared at a lower field around 85-90 ppm,
respectively. In the products derived from dimethyl substituted
â-lactam-4-ylidenes 2a-2e, the 4′′-H signal of 5-I was a sharp
singlet at about 6.0 ppm, whereas in 5-II the 4′′-H appeared as
a broad peak at 6.2 ppm. In addition to these NMR features of
4′′-C and 4′′-H between configurational isomers or diastereo-
mers, the 3′′-Me groups in two diastereomers of 6 can also be
easily distinguished. In the case of isomers 6-I, all of the methyl
proton signals were observed at the normal region (1.2-1.6
ppm); however, the proton of one of the four methyl groups in
isomer 6-II resonated at very high field (0.7-0.8 ppm). (See
the Supporting Information, table and NMR spectra.) This
shielding effect can be explained from the ChemBats3D
optimized structure of 6-II, which showed one methyl group
was exactly located in the shielding region of the N-substituted
phenyl ring. (See the Supporting Information, Figure 2.)
The formation of indolone derivatives 4, 5, and 6 can be best
explained by nucleophilic addition of â-lactam carbenes to
isocyanates. The resulting zwitterion 7 undergoes intramolecular
electrophilic substitution reaction to give intermediate 9. The
interaction of 9 with another isocyanate molecule affords product
4, while insertion of carbene to the N-H or O-H bond of the
tautomers 9 or 10 accounts for the formation of 5 and 6,
respectively (Scheme 2). The pathway from 9 to 4 was
confirmed by reaction of 9bc with isocyanate 3c under the
identical conditions of the reaction between 1b and 3c that
afforded 4bc as the sole product in 73% yield. The direct
formation of 5bc (27%) and 6bc (15%) from thermolysis of
carbene source 1b in the presence of 9bc gave evidence for the
mechanism depicted in Scheme 2. It should be noted that
â-lactam amidocarbene 2 exhibits different reactivity from
typical nucleophilic carbenes when treated with aryl isocyanates.
For example, most reactions between diheteroatom-substituted
carbenes and aryl isocyanates have been reported to afford
N,N-diarylimidazoline-2,4-dione (hydantoin) derivatives as
sole products,7 while only N,N- or N,S-substituted carbenes
were mentioned to form indolone products in very low yields
(13-39%).8a,12 On the contrary, however, only indolone deriva-
tives were obtained in our cases. Furthermore, the O-carbene
substituted indole-2-ones, the major products in our reactions,
have never before been reported in the reactions between typical
nucleophilic carbenes and aryl or vinyl isocyanates. The different
outcomes most probably originated from the different stability
and therefore the reactivity of the dipolar intermediates. The
dipolar intermediates derived from the addition of typical
nucleophilic carbenes to isocyanates are stabilized by two
heteroatoms. Therefore the carbon cation of this dipole is not
reactive to aromatic electrophilic substitution, and the nitrogen
anion, on the other hand, readily attacks the second molecule
of aryl isocyanate to form N,N-diarylimidazoline-2,4-dione
(hydantoin). In contrast, the less stable dipolar intermediate 7
derived from amidocarbenes prefers to undergo intramolecular
cyclization to form an indolone intermediate 9, which provides
products 4, 5, and 6 via different pathways.
yield (%)a
starting
entry materials products 5-I 5-II
5
6-I 6-II
6
6:5b total
1
2
3
4
5
6
7
8
1a, 3b 5ab, 6ab 12 11 23
1a, 3c 5ac, 6ac 13 13 26
1b, 3b 5bb, 6bb 14 12 26 26 16 42 1.6:1 68
1b, 3c 5bc, 6bc 16 17 33 49 1.5:1 82
1c, 3a 5ca, 6ca 11 12 23 26 16 42 1.8:1 65
1c, 3b 5cb, 6cb 18 14 32 19 15 34
1c, 3c 5cc, 6cc 15 18 33 19 14 33
1d, 3b 5db, 6db 10 19 29 31 26 57
47
2:1 70
45 1.7:1 71
1:1 66
1:1 66
2:1 86
9
1e, 3b 5eb, 6eb 12 15 27 26 19 45 1.7:1 72
10
11
1f, 3c
1g, 3c
5fc, 6fc
19 14 33 31 16 47 1.4:1 80
5gc, 6gc 17 16 33 29 14 43 1.3:1 76
a Isolated yield. b The ratio of product 6 over 5 was determined by
isolated yields.
FIGURE 1. Biologically active spiro[azetidine-4,3′-indoline]-2,2′-
diones.
column chromatography on silica gel. The pairs of two dia-
stereoisomers of 6ab, 6ac, and 6bc could not be separated by
column chromatography; fortunately, pure 6ab-I, 6ac-I, or 6bc-I
was precipitated respectively from their solution in a mixture
of petroleum ether and ethyl acetate. The structures of all
products were elucidated on the basis of spectroscopic data,
microanalysis, and X-ray diffraction studies. Thus, mass data
and elemental analyses indicated the product 4 derived from
one carbene and two isocyanate molecules (1+2 adduct) but 5
and 6 were the adducts of two carbene moieties to one
isocyanate (2+1 adduct), respectively. However, spectroscopic
data did not allow full verification of the structure. X-ray
diffraction studies then unambiguously confirmed that the
compound 5db-I (R ) Me, X ) Cl, Y ) CH3) was (R,R)- or
(S,S)-1′-(azetidine-2′′-one)spiro[azetidine-4,3′-indoline]-2,2′-di-
one, while 6eb-I (R ) Me, X ) Br, Y ) CH3) and 6gc-I (R )
Ph, X ) Br, Y ) Cl) were (R,R)- or (S,S)-2′-(azetidine-2′′-
one)oxyspiro[azetidine-4,3′-indolenine]-2-ones (see the Sup-
porting Information, Figure 1). No X-ray quality single crystals
were obtained for compound 4bc. The observations of a N-H
1
moiety in both the infrared and H NMR spectrum and of a
similar resonance pattern of the aromatic protons as that of 5bc
1
in the H NMR spectrum suggested the 1′-(p-chlorophenyl)-
carbamoyl spiro[azetidine-4,3′-indoline]-2,2′-dione structure for
4bc. The proposed structure of 4bc was also supported by the
chemical hydrolyses of 4bc, 5bc, and 6bc that all gave the same
spiro[azetidine-4,3′-indoline]-2,2′-dione product 9bc. The struc-
ture assignment of 4bc was further evidenced by preparation
of 4bc from the reaction of 9bc with isocyanate 3c (vide infra).
It has been reported that many spiro[azetidinone-4,3′-indo-
lones] derivatives are biologically active. For example, com-
(12) Er, H.-T.; Pole, D. L.; Warkentin, J. Can. J. Chem. 1996, 74, 1480.
4420 J. Org. Chem., Vol. 71, No. 12, 2006

Spiro[azetidinone-4,3′-indolinone] DeriVatiVes
SCHEME 2. The Proposed Mechanism for the Formation of Products 4, 5, and 6
pounds 1113a and 1213b have been found to exhibit significant
activity against maximal electroshock seizure, while compounds
1313c show fungicidal activity against Aspergillus flaVus, A.
niger, and Helminthosporium oryzae. Compound 1413d has been
reported to inhibit picornaviruses and human leukocyte elastase,
and compounds 1513e are active against gram-positive bacteria
(Figure 1). With products 4-6 in hand, we envisioned that the
removal of the N-substituent or O-substituent would easily give
analogues of those bioactive compounds. Treated with p-
toluenesulfonic acid in a hot chlorinated alkane solution, both
the N-substituted indolones 5bc and its O-substituted isomers
6bc were converted into spiro[azetidine-4,3′-indoline]-2,2′-dione
9bc in excellent yield, albeit the hydrolysis of the former needs
a higher temperature or longer reaction time than that of the
later. Hydrolysis of 4bc with sodium hydroxide in ethanol also
afforded 9bc. Finally, compound 9bc was prepared very
conveniently in good yield by refluxing 1b with 3c in toluene
followed by heating the resulting mixture with p-toluenesulfonic
acid in trichloroethane (Scheme 3 and Table 3). With our
method, 9fa14 readily prepared from 1f and 3a was converted
into bioactive compound 1113a in 60% yield with treatment of
diphenylacetyl chloride at room temperature (Scheme 4). Almost
all of the known methods for preparation of spiro[azetidinone-
4,3′-indolones] were based on the [2+2] cycloaddition of a
ketene with an imine that was yielded from the reaction of an
amine with an isatin.13,15 Since most of the substituted isatins
are not commercially available, the application of a known
literature method has been limited. The easy availability of
isocyanates under our cyclic carbene approach gives more
advantages in the synthesis of spiro[azetidinone-4,3′-indolones].
In summary, we have studied the nucleophilicity of cyclic
amidocarbenes, â-lactam-4-ylidenes. They are highly reactive
toward aryl isocyanates to form both N- and O-â-lactam
substituted spiro[azetidinone-4,3′-indolinone] derivatives. The
products have been further converted in good to excellent yields
into spiro[azetidinone-4,3′-indolinone], which was analogous to
the known biologically active compounds. We have revealed
the nucleophilic feature of cyclic amidocarbenes and demon-
strated their application in organic synthesis.
Experimental Section
General Procedure for Thermolysis of Spiro[â-lactam-4,3′-
oxadiazolines] 1 in the Presence of Aryl Isocyanates. Under
nitrogen atmosphere, a mixture of oxadiazolines 1 (6 mmol) and
aryl isocyanate 3 (3 mmol) was refluxed in toluene (80 mL) for 12
h. After removal of the solvent, the residue was subjected to
chromatography on a silica gel column eluting with a mixture of
petroleum ether (60-90 °C) and ethyl acetate (petroleum ether:
ethyl acetate from 10:1 to 3:1) to afford products 5 and 6. (Note:
4bc was also isolated from the reaction of 3 mmol of oxadiazoline
1b with 3 mmol of isocyanate 3c.)
(R,R)- and (S,S)-1′-(3′′,3′′-dimethyl-1′′-phenylazetidin-2′′-one)-
3,3,5′-trimethyl-1-phenylspiro[azetidine-4,3′-indoline]-2,2′-di-
1
one 5ab-I: mp 214-215 °C; IR V (cm-1) 1770, 1735, 1503; H
NMR (500 MHz) δ (ppm) 7.34-7.38 (m, 4H), 7.22 (t, J ) 7.6
Hz, 2H), 7.14 (t, J ) 7.0 Hz, 1H), 7.11 (s, 1H), 7.09 (d, J ) 8.4
Hz, 2H), 7.05 (d, J ) 10.8 Hz, 2H), 7.01 (d, J ) 8.2 Hz, 1H), 6.06
(s, 1H), 2.26 (s, 3H), 1.59 (s, 6H), 1.31 (s, 3H), 1.30 (s, 3H); 13C
NMR (125 MHz) δ (ppm) 174.6, 170.1, 169.9, 138.8, 137.3, 136.8,
132.8, 131.3, 129.6, 129.2, 126.8, 124.9, 124.4, 122.8, 117.0, 116.1,
112.2, 69.8, 69.1, 60.2, 57.3, 22.5, 21.1, 21.0, 18.5, 16.3; MS (EI)
70 (100), 119 (90), 146 (50), 479 (M+, 60%). Anal. Calcd for
C30H29N3O3: C 75.13, H 6.09, N 8.76. Found: C 75.11, H 6.35, N
8.67.
(13) (a) Singh, G. S.; Singh, T.; Lakhan, R. Indian J. Chem., Sect. B:
Org. Chem. Incl. Med. Chem. 1997, 36B (10), 951. (b) Singh, G. S.;
Siddiqui, N.; Pandeya, S. N. Boll. Chim. Farm. 1994, 133 (2), 76. (c) Kumar,
R.; Giri, S. N. J. Agric. Food Chem. 1989, 37 (4), 1094. (d) Skiles, J. W.;
McNeil, D. Tetrahetron Lett. 1990, 31 (50), 7277. (e) Joshi, K. C.; Jain,
R.; Sharma, V. J. Indian Chem. Soc. 1986, 63 (4), 430.
(15) (a) Dandia, A.; Singh, R.; Sharma, P. Heteroatom Chem. 2003, 14
(5), 468. (b) Azizian, J.; Sarrafi, Y.; Mehrdad, M.; Jadidi, K. Indian J.
Chem., Sect. B: Org. Chem. Incl. Med. Chem. 2000, 39B (4), 304. (c) Singh,
G. S.; Prakash, S. Indian J. Heterocycl. Chem. 1997, 7 (2), 145. (d) Joshi,
K. C.; Dandia, A.; Bhagat, S. J. Fluorine Chem. 1990, 48 (2), 169.
(14) Singh, G. S. Indian J. Heterocycl. Chem. 2001, 10, 235.
J. Org. Chem, Vol. 71, No. 12, 2006 4421

Cheng et al.
SCHEME 3. Preparation of Spiro[azetidine-4,3′-indoline]-2,2′-dione 9bc
TABLE 3. Preparation of Spiro[azetidine-4,3′-indoline]-2,2′-dione
131.1, 130.6, 129.6, 129.1, 126.0, 124.4, 124.3, 120.1, 116.5, 116.2,
89.9, 73.3, 58.7, 56.8, 21.7, 21.5, 19.8, 19.7, 17.2; MS (EI) 146
(100), 235 (25), 306 (10), 479 (M+, 10%). Anal. Calcd for
C30H29N3O3: C 75.13, H 6.09, N 8.76. Found: C 75.10, H 6.27, N
8.74.
9bc and 9fa
starting
material
reagent/
solvent
temp
(°C)
time
(h)
yield
(%)a
product
6bc
TsOH/CHCl3
TsOH/CHCl3
TsOH/TCEb
TsOH/CHCl3
TsOH/TCE
TsOH/Toluene
NaOH/EtOH
toluene
60-70
60-70
0.5
17
3
41
6
17
3
12
8
9bc
9bc
9bc
9bc
9bc
9bc
9bc
9bc
93
95
95
95
98
36
46
75c
The mixture of two diastereoisomers 6ab-II and 6ab-I (6ab-
5bc-I
5bc-I
5bc-II
5bc-II
5bc-II
4bc
1
II:6ab-I 2:1): IR V (cm-1) 1769, 1588, 1503; H NMR δ (500
110-120
60-70
MHz) (ppm) 7.49 (d, J ) 8.0 Hz, 2H, II), 7.38 (d, J ) 7.9 Hz, 1H
+ 0.5H, II + I), 7.35 (t, J ) 7.4 Hz, 2H, II), 7.25-7.32 (m, 2.5H,
II + I), 7.13-7.22 (m, 5H, II + I), 7.08 (d, J ) 7.7 Hz, 1H, I),
7.05 (t, J ) 7.5 Hz, 1H, II), 7.02 (d, J ) 7.8 Hz, 2H, II), 6.94 (d,
J ) 7.8 Hz, 0.5H, I), 6.90 (t, J ) 7.1 Hz, 1H, I), 6.86 (d, J ) 7.4
Hz, 1H, I), 6.66 (s, 1H, II), 6.00 (s, 0.5H, I), 2.38 (s, 3H + 1.5H,
II + I), 1.60 (s, 1.5H, I), 1.59 (s, 1.5H, I), 1.45 (s, 1.5H, I), 1.41
(s, 3H + 1.5H, II + I), 1.37 (s, 3H, II), 1.33 (s, 3H, II), 0.72 (s,
3H, II); 13C NMR (125 MHz) δ (ppm) 176.0, 175.3, 170.2, 169.8,
149.1, 137.3, 136.7, 136.1, 134.3, 131.0, 130.6, 130.3, 129.6, 129.2,
129.1, 125.9, 124.8, 124.4, 124.3, 120.7, 119.9, 117.4, 116.7, 116.5,
116.2, 89.9, 86.8, 59.1, 58.7, 56.8, 56.4, 22.1, 21.7, 21.5, 20.2, 19.8,
19.7, 19.0, 17.2, 15.9; MS (EI) 146 (100), 187 (15), 235 (15), 479
(M+, 15%). Anal. Calcd for C30H29N3O3: C 75.13, H 6.09, N 8.76.
Found: C 74.92, H 6.10, N 8.65.
110-120
110-120
70-80
110-120
110-120
110-120
110-120
1b, 3c
TsOH/TCE
toluene
TsOH/TCE
1f, 3a
12
8
9fa
68
a Isolated yield. b TCE ) trichloroethane. c A mixture of 1b and 3c was
refluxed in toluene for 12 h, and after removal of toluene then another 8 h
with TsOH in trichloroethane.
(R,S)- and (S,R)-1′-(3′′,3′′-dimethyl-1′′-phenylazetidin-2′′-one)-
3,3,5′-trimethyl-1-phenylspiro[azetidine-4,3′-indoline]-2,2′-di-
1
one 5ab-II: mp 249-250 °C; IR V (cm-1) 1761, 1727, 1503; H
(R,R)- and (S,S)-1′-(3′′,3′′-dimethyl-1′′-phenylazetidin-2′′-one)-
5′-chloro-3,3,-dimethyl-1-phenylspiro[azetidine-4,3′-indoline]-
2,2′-dione 5ac-I: mp 253-255 °C; IR V (cm-1) 1772, 1736, 1600;
1H NMR (500 MHz) δ (ppm) 7.35-7.36 (d, J ) 3.6 Hz, 4H), 7.29
(s, 1H), 7.23-7.26 (m, 3H), 7.16-7.18 (m, 1H), 7.11 (d, J ) 7.4
Hz, 1H), 7.05-7.08 (m, 3H), 6.05 (s, 1H), 1.60 (s, 3H), 1.59 (s,
3H), 1.33 (s, 3H), 1.30 (s, 3H); 13C NMR (125 MHz) δ (ppm)
174.1, 169.8, 169.3, 139.7, 137.0, 136.5, 130.9, 129.7, 129.3, 129.0,
126.3, 125.2, 124.9, 124.7, 116.9, 116.0, 113.3, 69.9, 68.8, 60.8,
57.4, 22.5, 21.2, 18.5, 16.3; MS (EI) 119 (72), 146 (100), 499 (M+,
6%)/501 (2). Anal. Calcd for C29H26ClN3O3: C 69.66, H 5.24, N
8.40. Found: C 69.49, H 5.34, N 8.35.
(R,S)- and (S,R)-1′-(3′′,3′′-dimethyl-1′′-phenylazetidin-2′′-one)-
5′-chloro-3,3,-dimethyl-1-phenylspiro[azetidine-4,3′-indoline]-
2,2′-dione 5ac-II: mp 284-285 °C; IR V (cm-1) 1762, 1731, 1603;
1H NMR (500 MHz) δ (ppm) 7.34 (s, 4H), 7.27 (s, 1H), 7.22 (t, J
) 7.8 Hz, 3H), 7.19 (br s, 1H), 7.10 (t, J ) 8.5 Hz, 2H), 6.99 (d,
NMR (500 MHz) δ (ppm) 7.31-7.36 (m, 4H), 7.19 (t, J ) 7.7
Hz, 2H), 7.15 (t, J ) 7.0 Hz, 1H), 7.08 (d, J ) 7.2 Hz, 2H), 7.05
(s, 2H), 7.01 (d, J ) 7.7 Hz, 2H), 6.28 (brs, 1H), 2.24 (s, 3H),
1.61 (s, 3H), 1.52 (br s, 3H), 1.35 (s, 6H); 13C NMR (125 MHz) δ
(ppm) 175.3, 169.9 (2 CO), 138.7, 137.0, 136.8, 132.8, 131.2, 129.6,
129.2, 126.6, 124.8, 124.3, 122.7, 117.0, 116.3, 116.1, 112.5, 69.0,
68.6, 60.0, 56.6, 23.0, 21.02, 20.95, 18.5, 16.6; MS (EI) 146 (90),
479 (M+, 100%). Anal. Calcd for C30H29N3O3: C 75.13, H 6.09,
N 8.76. Found: C 74.92, H 6.39, N 8.67.
(R,R)- and (S,S)-2′-(3′′,3′′-dimethyl-1′′-phenylazetidin-2′′-one)-
oxy-3,3,5′-trimethyl-1-phenylspiro[azetidine-4,3′-indolenine]-2-
one 6ab-I: mp 219-220 °C; IR V (cm-1) 1769, 1762, 1587, 1504;
1H NMR (300 MHz) δ (ppm) 7.36 (d, J ) 7.8 Hz, 1H), 7.24-7.32
(m, 3H), 7.19 (s, 1H), 7.15 (t, J ) 7.4 Hz, 1H), 7.08 (d, J ) 7.7
Hz, 2H), 6.83-6.98 (m, 5H), 5.99 (s, 1H), 2.38 (s, 3H), 1.59 (s,
3H), 1.59 (s, 3H), 1.44 (s, 3H), 1.40 (s, 3H); 13C NMR (125
MHz) δ (ppm) 175.3, 170.1, 169.7, 149.2, 137.7, 136.7, 134.4,
4422 J. Org. Chem., Vol. 71, No. 12, 2006

Spiro[azetidinone-4,3′-indolinone] DeriVatiVes
SCHEME 4. Preparation of 1′-Diphenylacetyl-3,3,-diphenylspiro[azetidine-4,3′-indoline]-2,2′-dione 11
J ) 8.3 Hz, 2H), 6.27 (br s, 1H), 1.62 (s, 3H), 1.52 (s, 3H), 1.37
(s, 3H), 1.34 (s, 3H); 13C NMR (125 MHz) δ (ppm) 174.8, 169.7,
169.4, 139.6, 136.7, 136.5, 130.8, 129.7, 129.3, 129.0, 126.1, 125.1,
124.8, 124.6, 116.9, 116.1, 113.6, 68.6 (4-C and 4′′-C), 60.6, 56.7,
22.9, 21.1, 18.4, 16.6; MS (EI) 119 (60), 146 (100), 499 (M+, 4%).
Anal. Calcd for C29H26ClN3O3: C 69.66, H 5.24, N 8.40. Found:
C 69.32, H 5.48, N 8.29.
(R,R)- and (S,S)-2′-(3′′,3′′-dimethyl-1′′-phenylazetidin-2′′-one)-
oxy-5′-chloro-3,3,-dimethyl-1-phenylspiro[azetidine-4,3′-indole-
nine]-2-one 6ac-I: mp 217-218 °C; IR V (cm-1) 1763, 1601, 1583;
1H NMR (500 MHz) δ (ppm) 7.42-7.46 (m, 2H), 7.37 (s, 1H),
7.32 (t, J ) 7.9 Hz, 2H), 7.19 (t, J ) 7.4 Hz, 1H), 7.06 (d, J ) 8.0
Hz, 2H), 6.97 (t, J ) 7.2 Hz, 1H), 6.91 (t, J ) 7.9 Hz, 2H), 6.85
(d, J ) 7.8 Hz, 2H), 6.00 (s, 1H), 1.61 (s, 3H), 1.59 (s, 3H), 1.46
(s, 3H), 1.41 (s, 3H); 13C NMR (125 MHz) δ (ppm) 176.3, 169.5,
169.4, 150.1, 137.4, 136.6, 132.4, 130.7, 130.4, 129.8, 129.2, 125.4,
124.7, 124.4, 121.4, 116.5, 116.1, 90.3, 73.3, 59.4, 56.9, 21.9, 19.7
(2 CH3), 17.2; MS (EI) 129 (82), 144 (100), 174 (75), 254 (40),
499 (M+, 25)/501 (7). Anal. Calcd for C29H26ClN3O3: C 69.66, H
5.24, N 8.40. Found: C 69.45, H 5.40, N 8.39.
138.8, 134.6, 134.45, 134.38, 133.9, 132.6, 131.2, 130.0, 129.7,
126.6, 122.8, 117.0, 116.2, 112.4, 69.0, 68.6, 59.9, 56.6, 22.9, 21.01,
20.95, 18.5, 16.6; MS (EI) 91 (55), 133 (35), 160 (60), 507 (M+,
100)/508 (35, M + 1). Anal. Calcd for C32H33N3O3: C 75.71, H
6.55, N 8.28. Found: C 75.75, H 7.01, N 8.42.
(R,R)- and (S,S)-2′-(3′′,3′′-dimethyl-1′′-methylphenylazetidin-
2′′-one)oxy-3,3,5′-trimethyl-1-methylphenylspiro[azetidine-4,3′-
indolenine]-2-one 6bb-I: mp 241-243 °C; IR V (cm-1) 1765, 1581,
1518; 1H NMR (300 MHz) δ (ppm) 7.36 (d, J ) 7.8 Hz, 1H), 7.24
(d, J ) 7.8 Hz, 1H), 7.17 (s, 1H), 7.08 (d, J ) 8.3 Hz, 2H), 6.97
(d, J ) 8.5 Hz, 2H), 6.76 (d, J ) 8.5 Hz, 2H), 6.69 (d, J ) 8.3 Hz,
2H), 5.96 (s, 1H), 2.37 (s, 3H), 2.34 (s, 3H), 2.23 (s, 3H), 1.58 (s,
3H), 1.57 (s, 3H), 1.43 (s. 3H), 1.39 (s, 3H); 13C NMR (125 MHz)
δ (ppm) 175.5, 169.9, 169.5, 149.2, 135.2, 134.32, 134.26, 133.9,
131.0, 130.7, 130.0, 129.5, 125.9, 120.0, 117.1, 116.6, 116.2, 90.0,
73.3, 58.7, 56.7, 21.7, 21.5, 20.9, 19.80, 19.77, 17.2; MS (EI) 91
(78), 144 (45), 160 (100), 507 (M+, 17)/508 (7). Anal. Calcd for
C32H33N3O3: C 75.71, H 6.55, N 8.28. Found: C 75.73, H 6.85, N
8.03.
(R,S)- and (S,R)-2′-(3′′,3′′-dimethyl-1′′-methylphenylazetidin-
2′′-one)oxy-3,3,5′-trimethyl-1-methylphenylspiro[azetidine-4,3′-
indolenine]-2-one 6bb-II: mp 213-214 °C; IR V (cm-1) 1777, 1760,
The mixture of two diastereoisomers 6ac-II and 6ac-I (6ac-
1
II:6ac-I 1:0.9): IR V (cm-1) 1778, 1766, 1600, 1581; H NMR
1
(500 MHz) δ (ppm) 7.42-7.47 (m, 4H + 1.8H, II + I), 7.34-
3.77 (m, 3H + 0.9H, II + I), 7.32 (t, J ) 7.9 Hz, 1.8H, I), 7.23 (d,
J ) 8.0 Hz, 1H, II), 7.19 (d, J ) 8.8 Hz, 1H, II), 7.16 (t, J ) 7.1
Hz, 0.9H, I), 7.05-7.09 (m, 2H + 0.9H, II + I), 7.00 (d, J ) 7.8
Hz, 2H, II), 6.96 (t, J ) 7.2 Hz, 0.9H, I), 6.91 (t, J ) 7.9 Hz,
1.8H, I), 6.86 (d, J ) 7.8 Hz, 1.8H, I), 6.66 (s, 1H, II), 6.00 (s,
0.9H, I), 1.61 (s, 2.7H, I), 1.59 (s, 2.7H, I), 1.46 (s, 2.7H, I), 1.42
(s, 3H, II), 1.41 (s, 2.7H, I), 1.38 (s, 3H, II), 1.34 (s, 3H, II), 0.73
(s, 3H); 13C NMR (125 MHz) δ (ppm) 176.9, 176.3, 169.6, 169.4,
150.0, 137.4, 137.1, 136.6, 136.0, 132.4, 132.1, 130.74, 130.69,
130.4, 130.3, 129.8, 129.3, 129.22, 129.16, 125.44, 125.39, 125.0,
124.7, 124.6, 124.4, 121.4, 121.2, 117.3, 116.6, 116.5, 116.1, 90.3,
87.2, 59.7, 59.4, 56.9, 56.5, 22.2, 21.9, 20.2, 19.7, 18.9, 17.2, 15.9;
MS (EI) 119 (60), 146 (100), 192 (53), 499 (15)/501 (5). Anal.
Calcd for C29H26ClN3O3: C 69.66, H 5.24, N 8.40. Found: C 69.50,
H 5.38, N 8.37.
1588, 1517; H NMR (500 MHz) δ (ppm) 7.37 (d, J ) 8.1 Hz,
3H), 7.26 (d, J ) 8.1 Hz, 1H), 7.15 (s, 1H), 7.14 (d, J ) 8.2 Hz,
2H), 6.99 (d, J ) 8.3 Hz, 2H), 6.91 (d, J ) 8.4 Hz, 2H), 6.60 (s,
1H), 2.37 (s, 3H), 2.33 (s, 3H), 2.26 (s, 3H), 1.39 (s, 3H), 1.38 (s,
3H), 1.34 (s, 3H), 0.76 (s, 3H); 13C NMR (125 MHz) δ (ppm)
176.1, 169.9, 169.6, 149.2, 134.9, 134.5, 134.2, 134.1, 133.6, 130.9,
130.5, 130.0, 129.6, 125.9, 119.7, 117.4, 116.7, 87.0, 73.2, 59.0,
56.4, 22.1, 21.4, 20.94, 20.86, 20.2, 19.1, 16.1; MS (EI) 91 (55),
133 (80), 160 (100), 507 (M+, 13)/508 (4). Anal. Calcd for
C32H33N3O3: C 75.71, H 6.55, N 8.28. Found: C 75.28, H 6.30, N
8.25.
1′-(p-Chlorophenyl)carbamoyl-5′-chloro-3,3-dimethyl-1-(p-
methylphenyl)spiro[azetidine-4,3′-indoline]-2,2′-dione 4bc: mp
206-207 °C; IR V (cm-1) 3251, 1769, 1745, 1598, 1549; 1H NMR
(500 MHz) δ (ppm) 10.45 (s, 1H), 8.42 (d, J ) 8.8 Hz, 1H), 7.56
(d, J ) 8.7 Hz, 2H), 7.50 (d, J ) 8.8 Hz, 1H), 7.37 (d, J ) 8.4 Hz,
2H), 7.36 (s, 1H), 7.07 (d, J ) 8.2 Hz, 2H), 6.96 (d, J ) 8.2 Hz,
2H), 2.28 (s, 3H), 1.53 (s, 3H), 1.38 (s, 3H); 13C NMR (125 MHz)
δ (ppm) 176.3, 169.0, 148.4, 138.5, 135.1, 134.8, 133.6, 131.1,
130.9, 130.1, 130.0, 129.3, 125.5, 124.2, 121.7, 118.3, 117.0, 62.1,
48.8, 20.89, 20.87, 18.3; MS (EI) 153 (82), 192 (85), 207 (85),
242 (90), 270 (100), 340 (85), 493 (M+, 5%). Anal. Calcd for
C26H21Cl2N3O3: C 63.17, H 4.28, N 8.50. Found: C 63.18, H 4.62,
N 8.34.
(R,R)- and (S,S)-1′-(3′′,3′′-dimethyl-1′′-methylphenylazetidin-
2′′-one)-3,3,5′-trimethyl-1-methylphenylspiro[azetidine-4,3′-in-
doline]-2,2′-dione 5bb-I: mp 179-181°C; IR V (cm-1) 1758, 1725,
1
1519, 1488; H NMR (300 MHz) δ (ppm) 7.25 (d, J ) 8.3 Hz,
2H), 7.13 (d, J ) 8.3 Hz, 2H), 7.09 (s, 1H), 6.96-7.05 (m, 6H),
6.02 (s, 1H), 2.30 (s, 3H), 2.26 (s, 3H), 2.25 (s, 3H), 1.57 (s, 6H),
1.29 (s, 6H); 13C NMR (125 MHz) δ (ppm) 174.7, 169.9, 169.7,
138.9, 134.8, 134.6, 134.3, 134.1, 132.6, 131.3, 130.1, 129.7, 126.7,
122.9, 116.9, 116.0, 112.2, 69.8, 69.1, 60.1, 57.2, 22.5, 21.1, 21.0,
20.92, 20.85, 18.5, 16.3; MS (EI) 70 (100), 91 (88), 132 (62), 133
(100), 160 (65), 507 (40)/508 (15, M + 1). Anal. Calcd for
C32H33N3O3: C 75.71, H 6.55, N 8.28. Found: C 75.73, H 6.75, N
8.29.
(R,R)- and (S,S)-1′-(3′′,3′′-dimethyl-1′′-methylphenylazetidin-
2′′-one)-5′-chloro-3,3,-dimethyl-1-methylphenylspiro[azetidine-
4,3′-indoline]-2,2′-dione 5bc-I: mp 291-292 °C; IR V (cm-1) 1758,
1
1725, 1519, 1489; H NMR (500 MHz) δ (ppm) 7.18 (d, J ) 1.5
Hz, 1H), 7.14 (d, J ) 8.3 Hz, 3H), 7.05 (d, J ) 8.2 Hz, 2H), 6.95
(d, J ) 8.4 Hz, 3H), 6.87 (d, J ) 8.3 Hz, 2H), 5.93 (s, 1H), 2.23
(s, 3H), 2.19 (s, 3H), 1.49 (s, 3H), 1.48 (s, 3H), 1.22 (s, 3H), 1.19
(s, 3H); 13C NMR (75 MHz) δ (ppm) 174.2, 169.6, 169.1, 139.8,
134.9, 134.6, 134.4, 134.0, 130.8, 130.2, 129.8, 128.8, 126.2, 125.0,
116.9, 115.9, 113.3, 69.9, 68.8, 60.7, 57.3, 22.4, 21.1, 20.9, 20.8,
18.5, 16.3; MS (EI) 160 (100), 527 (M+, 10%)/529 (3). Anal. Calcd
for C31H30ClN3O3: C 70.51, H 5.73, N 7.96. Found: C 70.56, H
6.09, N 7.85.
(R,S)- and (S,R)-1′-(3′′,3′′-dimethyl-1′′-methylphenylazetidin-
2′′-one)-3,3,5′-trimethyl-1-methylphenylspiro[azetidine-4,3′-in-
doline]-2,2′-dione 5bb-II: mp 238-239 °C; IR V (cm-1) 1762,
1
1730, 1518, 1488; H NMR (500 MHz) δ (ppm) 7.24 (d, J ) 8.1
Hz, 2H), 7.11 (d, J ) 8.2 Hz, 2H), 7.07 (s, 1H), 7.03 (s, 2H), 6.98
(d, J ) 8.2 Hz, 2H), 6.91 (d, J ) 8.3 Hz, 2H), 6.23 (br s, 1H), 2.34
(s, 3H), 2.30 (s, 3H), 2.24 (s, 3H), 1.59 (s, 3H), 1.50 (br s, 3H),
1.33 (s, 6H); 13C NMR (125 MHz) δ (ppm) 175.3, 169.7 (2 CO),
J. Org. Chem, Vol. 71, No. 12, 2006 4423

Cheng et al.
(R,S)- and (S,R)-1′-(3′′,3′′-dimethyl-1′′-methylphenylazetidin-
2′′-one)-5′-chloro-3,3,-dimethyl-1-methylphenylspiro[azetidine-
(M+, 45%)/526 (15). Anal. Calcd for C31H31N3O5: C 70.84, H 5.94,
N 7.99. Found: C 70.94, H 6.30, N 7.99.
4,3′-indoline]-2,2′-dione 5bc-II: mp 248-249 °C; IR V (cm-1
)
(R,R)- and (S,S)-2′-(3′′,3′′-dimethyl-1′′-methoxyphenylazeti-
din-2′′-one)oxy-3,3-dimethyl-1-methoxyphenylspiro[azetidine-
4,3′-indolenine]-2-one 6ca-I: mp 193-194 °C; IR V (cm-1) 1763,
1
1763, 1739, 1519; H NMR (500 MHz) δ (ppm) 7.07-7.16 (m,
4H), 7.04 (d, J ) 8.4 Hz, 2H), 6.98 (d, J ) 8.4 Hz, 1H), 6.92 (d,
J ) 8.5 Hz, 2H), 6.80 (d, J ) 8.4 Hz, 2H), 6.14 (br s, 1H), 2.26 (s,
3H), 2.22 (s, 3H), 1.51 (s, 3H), 1.42 (br s, 3H), 1.25 (s, 3H), 1.22
(s, 3H); 13C NMR (125 MHz) δ (ppm) 174.8, 169.5, 169.2, 139.7,
134.8, 134.4, 134.3, 134.1, 130.7, 130.2, 129.8, 128.9, 126.1, 124.9,
116.9, 116.1, 113.6, 68.7 (4-C and 4′′-C), 60.5, 56.7, 22.8, 21.05,
21.02, 20.95, 18.4, 16.6; MS (EI) 394 (65), 457 (100)/459(35), 527
(M+,6%)/529 (2). Anal. Calcd for C31H30ClN3O3: C 70.51, H 5.73,
N 7.96. Found: C 70.51, H 5.93, N 7.83.
1
1577, 1513; H NMR (500 MHz) δ (ppm) 7.46-7.49 (m, 2H),
7.38 (d, J ) 7.4 Hz, 1H), 7.19 (t, J ) 7.2 Hz, 1H), 7.00 (d, J ) 9.0
Hz, 2H), 6.83 (d, J ) 8.9 Hz, 2H), 6.79 (d, J ) 9.0 Hz, 2H), 6.48
(d, J ) 8.9 Hz, 2H), 6.01 (s, 1H), 3.77 (s, 3H), 3.73 (s, 3H), 1.61
(s, 3H), 1.58 (s, 3H), 1.44 (s, 3H), 1.40 (s, 3H); 13C NMR (125
MHz) δ (ppm) 176.3, 169.6, 169.2, 156.3, 156.2, 151.7, 131.1,
130.7, 130.6, 130.2, 125.1, 124.5, 120.4, 118.0, 117.6, 114.7, 114.3,
90.2, 73.5, 58.9, 56.8, 55.4, 55.3, 21.8, 19.80, 19.77, 17.3; MS (EI)
134 (75), 149 (95), 176 (100), 227 (100), 525 (M+, 50%)/ 526
(17). Anal. Calcd for C31H31N3O5: C 70.84, H 5.94, N 7.99.
Found: C 70.95, H 6.10, N 7.95.
(R,R)- and (S,S)-2′-(3′′,3′′-dimethyl-1′′-methylphenylazetidin-
2′′-one)oxy-5′-chloro-3,3-dimethyl-1-methylphenylspiro[azetidine-
4,3′-indolenine]-2-one 6bc-I: mp 225-226 °C; IR V (cm-1) 1765,
1
(R,S)- and (S,R)-2′-(3′′,3′′-dimethyl-1′′-methoxyphenylazeti-
din-2′′-one)oxy-3,3-dimethyl-1-methoxyphenylspiro[azetidine-
4,3′-indolenine]-2-one 6ca-II: mp 144-145 °C; IR V (cm-1) 1768,
1578, 1517; H NMR (500 MHz) δ (ppm) 7.44 (d, J ) 8.2 Hz,
1H), 7.42 (d, J ) 8.2 Hz, 1H), 7.35 (s, 1H), 7.10 (d, J ) 8.3 Hz,
2H), 6.94 (d, J ) 8.4 Hz, 2H), 6.76 (d, J ) 8.4 Hz, 2H), 6.70 (d,
J ) 8.3 Hz, 2H), 5.97 (s, 1H), 2.35 (s, 3H), 2.23 (s, 3H), 1.59 (s,
3H), 1.57 (s, 3H), 1.45 (s, 3H), 1.39 (s, 3H); 13C NMR (125 MHz)
δ (ppm) 176.5, 169.33, 169.28, 150.1, 135.0, 134.2, 134.0, 132.6,
130.7, 130.3, 130.1, 129.7, 129.5, 125.4, 121.3, 116.5, 116.1, 90.4,
73.3, 59.3, 56.8, 21.9, 21.0 (2 CH3), 19.8, 19.7, 17.3; MS (EI) 90
(100), 118 (75), 160 (75), 269 (40), 324 (30), 527 (M+, 15%)/529
(5%). Anal. Calcd for C31H30ClN3O3: C 70.51, H 5.73, N 7.96.
Found: C 70.18, H 5.91, N 7.83.
1
1588, 1514; H NMR (500 MHz) δ (ppm) 7.45-7.48 (m, 2H),
7.40 (d, J ) 8.7 Hz, 2H), 7.35 (d, J ) 7.4 Hz, 1H), 7.18 (t, J ) 7.2
Hz, 1H), 6.94 (d, J ) 8.8 Hz, 2H), 6.86 (d, J ) 8.8 Hz, 2H), 6.71
(d, J ) 8.9 Hz, 2H), 6.60 (s, 1H), 3.79 (s, 3H), 3.72 (s, 3H), 1.38
(s, 6H), 1.31 (s, 3H), 0.76 (s, 3H); 13C NMR (125 MHz) δ (ppm)
176.8, 169.6, 169.3, 156.8, 156.4, 151.7, 130.8, 130.6, 130.4, 129.4,
125.1, 124.5, 120.2, 119.0, 118.1, 114.39, 114.36, 87.2, 73.4, 59.2,
56.4, 55.5, 55.4, 22.1, 20.2, 19.0, 16.1; MS (EI) 134 (100), 145
(85), 176 (100), 227 (45), 525 (M+,35%)/526 (12). Anal. Calcd
for C31H31N3O5: C 70.84, H 5.94, N 7.99. Found: C 70.51, H
6.26, N 7.92.
The mixture of two diastereoisomers 6bc-II and 6bc-I
1
(6bc-II:6bc-I 2:1): IR V (cm-1) 1767, 1582, 1517; H NMR (500
MHz) δ (ppm) 7.40-7.45 (m, 3H, I + II), 7.32-7.36 (m, 3.5H, I
+ II), 7.15 (d, J ) 8.2 Hz, 2H, II), 7.10 (d, J ) 8.3 Hz, 1H, I),
7.00 (d, J ) 8.3 Hz, 2H, II), 6.94 (d, J ) 8.4 Hz, 1H, I), 6.88 (d,
J ) 8.4 Hz, 2H, II), 6.76 (d, J ) 8.4 Hz, 1H, I), 6.70 (d, J )
8.3 Hz, 1H, I), 6.60 (s, 1H, II), 5.97 (s, 0.5H, I), 2.35 (s, 1.5H, I),
2.33 (s, 3H, II), 2.26 (s, 3H, II), 2.23 (s, 1.5H, I), 1.59 (s, 1.5H, I),
1.52 (s, 1.5H, I), 1.44 (s, 1.5H, I), 1.40 (s, 3H, II), 1.39 (s, 3H, II),
1.34 (s, 3H, II), 0.76 (s, 3H, II); 13C NMR (125 MHz) δ (ppm)
176.9, 176.5, 169.5, 169.4, 150.1, 134.7, 134.6, 134.4, 133.5, 132.3,
130.7, 130.6, 130.3, 130.1, 129.9, 129.7, 129.5, 125.4, 125.3, 121.3,
121.1, 117.3, 117.0, 116.6, 116.1, 111.8, 90.4, 87.3, 73.2, 59.6,
59.3, 56.8, 56.5, 22.2, 21.8, 21.2, 21.1, 21.0, 20.9, 20.2, 19.7, 19.0,
18.6, 18.1, 17.3, 16.1; MS (EI) 159 (100)/160 (55), 527 (M+, 10%)/
529 (3).
(R,R)- and (S,S)-1′-(3′′,3′′-dimethyl-1′′-methoxyphenylazeti-
din-2′′-one)-3,3,5′-trimethyl-1-methoxyphenylspiro[azetidine-
4,3′-indoline]-2,2′-dione 5cb-I: mp 202-203 °C; IR V (cm-1
)
1
1765, 1722, 1514; H NMR (300 MHz) δ (ppm) 7.30 (d, J ) 9.0
Hz, 2H), 7.11 (s, 1H), 7.04 (d, J ) 8.9 Hz, 3H), 6.99 (d, J ) 8.2
Hz, 1H), 6.86 (d, J ) 8.9 Hz, 2H), 6.75 (d, J ) 9.0 Hz, 2H), 6.00
(s, 1H), 3.78 (s, 3H), 3.74 (s, 3H), 2.26 (s, 3H), 1.57 (s, 3H), 1.56
(s, 3H), 1.29 (s, 3H), 1.26 (s, 3H); 13C NMR (125 MHz) δ (ppm)
174.8, 169.6, 169.5, 156.7, 156.4, 138.9, 132.7, 131.3, 130.7, 130.2,
126.7, 123.0, 118.6, 117.5, 114.8, 114.4, 112.3, 70.0, 69.3, 60.2,
57.2, 55.5 (2 OCH3), 22.5, 21.1, 21.0, 18.6, 16.3; MS (EI) 134
(62), 149 (95), 241 (35), 539 (100)/540 (30). Anal. Calcd for
C32H33N3O5: C 71.23, H 6.16, N 7.79. Found: C 71.13, H 6.51, N
7.73.
(R,R)- and (S,S)-1′-(3′′,3′′-dimethyl-1′′-methoxyphenylazeti-
din-2′′-one)-3,3,-dimethyl-1-methoxyphenylspiro[azetidine-4,3′-
indoline]-2,2′-dione 5ca-I: mp 220-221 °C; IR V (cm-1) 1759,
(R,S)- and (S,R)-1′-(3′′,3′′-dimethyl-1′′-methoxyphenylazeti-
din-2′′-one)-3,3,5′-trimethyl-1-methoxyphenylspiro[azetidine-
4,3′-indoline]-2,2′-dione 5cb-II: mp 235-236 °C; IR V (cm-1
)
1
1729, 1514; H NMR (500 MHz) δ (ppm) 7.31 (d, J ) 8.5 Hz,
1
1762, 1721, 1513; H NMR (500 MHz) δ (ppm) 7.26 (d, J ) 8.9
Hz, 2H), 7.09 (s, 1H), 7.03 (br s, 2H), 6.95 (d, J ) 8.2 Hz, 2H),
6.83 (d, J ) 8.9 Hz, 2H), 6.72 (d, J ) 9.0 Hz, 2H), 6.21 (br s, 1H),
3.79 (s, 3H), 3.77 (s, 3H), 2.26 (s, 3H), 1.59 (s, 3H), 1.50 (br s,
3H), 1.33 (s, 6H); 13C NMR (125 MHz) δ (ppm) 175.4, 169.6 (2
CO), 156.6, 156.3, 138.8, 132.7, 131.2, 130.4, 130.3, 126.6, 122.8,
118.6, 117.6, 114.7, 114.4, 112.5, 69.2, 68.7, 60.0, 56.6, 55.4 (2
OCH3), 23.0, 21.04, 20.98, 18.5, 16.6; MS (EI) 134 (60), 149 (100),
539 (M+, 90)/540 (25). Anal. Calcd for C32H33N3O5: C 71.23, H
6.16, N 7.79. Found: C 71.14, H 6.04, N 7.96.
3H), 7.25 (d, J ) 7.6 Hz, 1H), 7.11 (d, J ) 8.1 Hz, 1H), 7.07 (d,
J ) 7.5 Hz, 1H), 7.03 (d, J ) 8.7 Hz, 2H), 6.87 (d, J ) 8.8 Hz,
2H), 6.74 (d, J ) 8.9 Hz, 2H), 6.02 (s, 1H), 3.79 (s, 3H), 3.75 (s,
3H), 1.58 (s, 3H), 1.57 (s, 3H), 1.28 (s, 3H), 1.26 (s, 3H); 13C
NMR (125 MHz) δ (ppm) 174.9, 169.54, 169.48, 156.8, 156.5,
141.4, 130.9, 130.7, 130.1, 126.1, 123.0, 118.7, 117.5, 114.8, 114.6,
114.4, 112.5, 70.1, 69.3, 60.3, 57.2, 55.5 (2 OCH3), 22.5, 21.1,
18.5, 16.3; MS (EI) 134 (40), 149 (60), 176 (45), 227 (100), 525
(M+, 20%)/526 (5). Anal. Calcd for C31H31N3O5: C 70.84, H 5.94,
N 7.99. Found: C 70.62, H 6.40, N 7.80.
(R,R)- and (S,S)-2′-(3′′,3′′-dimethyl-1′′-methoxyphenylazeti-
din-2′′-one)oxy-3,3,5′-trimethyl-1-methoxyphenylspiro[azetidine-
4,3′-indolenine]-2-one 6cb-I: mp 219-220 °C; IR V (cm-1) 1767,
(R,S)- and (S,R)-1′-(3′′,3′′-dimethyl-1′′-methoxyphenylazeti-
din-2′′-one)-3,3,-dimethyl-1-methoxyphenylspiro[azetidine-4,3′-
indoline]-2,2′-dione 5ca-II: mp 268-269 °C; IR V (cm-1) 1762,
1
1585, 1514; H NMR (500 MHz) δ (ppm) 7.35 (d, J ) 7.8 Hz,
1
1721, 1513; H NMR (500 MHz) δ (ppm) 7.25-7.30 (m, 4H),
1H), 7.24 (d, J ) 7.8 Hz, 1H), 7.18 (s, 1H), 7.01 (d, J ) 9.0 Hz,
2H), 6.82 (d, J ) 9.4 Hz, 2H), 6.80 (d, J ) 9.4 Hz, 2H), 6.48 (d,
J ) 9.0 Hz, 2H), 5.99 (s, 1H), 3.77 (s, 3H), 3.73 (s, 3H), 2.38 (s,
3H), 1.59 (s, 3H), 1.57 (s, 3H), 1.44 (s, 3H), 1.39 (s, 3H); 13C
NMR (125 MHz) δ (ppm) 175.6, 169.6, 169.2, 156.3, 156.2, 149.2,
134.3, 131.2, 131.0, 130.7, 130.2, 125.9, 120.0, 118.0, 117.6, 114.7,
114.4, 90.0, 73.4, 58.8, 56.7, 55.4, 55.3, 21.8, 21.5, 19.8 (2 CH3),
17.3; MS (EI) 134 (60), 149 (52), 176 (100), 241 (62), 539 (M+,
7.14 (d, J ) 7.8 Hz, 1H), 7.04 (t, J ) 6.7 Hz, 1H), 6.94 (d, J ) 8.7
Hz, 2H), 6.82 (d, J ) 8.7 Hz, 2H), 6.71 (d, J ) 8.8 Hz, 2H), 6.23
(br s, 1H), 3.78 (s, 3H), 3.75 (s, 3H), 1.60 (s, 3H), 1.51 (br s, 3H),
1.34 (s, 6H); 13C NMR (125 MHz) δ (ppm) 175.5, 169.5, 169.3,
156.7, 156.4, 141.3, 130.7, 130.3, 130.2, 126.0, 123.0, 122.8, 118.7,
117.6, 114.7, 114.4, 112.7, 69.2, 68.8, 60.2, 56.6, 55.4 (2 OCH3),
23.0, 21.0, 18.4, 16.6; MS (EI) 149 (98), 176 (70), 227 (100), 525
4424 J. Org. Chem., Vol. 71, No. 12, 2006

Spiro[azetidinone-4,3′-indolinone] DeriVatiVes
40%)/540 (20). Anal. Calcd for C32H33N3O5: C 71.23, H 6.16, N
7.79. Found: C 71.20, H 6.41, N 7.78.
(R,R)- and (S,S)-1′-(3′′,3′′-dimethyl-1′′-chlorophenylazetidin-
2′′-one)-3,3,5′-trimethyl-1-chlorophenylspiro[azetidine-4,3′-in-
doline]-2,2′-dione 5db-I: mp 252-253 °C; IR V (cm-1) 1764, 1727,
1596, 1496; 1H NMR (300 MHz) δ (ppm) 7.30 (s, 4H), 7.18 (d, J
) 8.9 Hz, 2H), 7.11 (s, 1H), 7.07 (d, J ) 8.3 Hz, 1H), 7.02 (d, J
) 8.9 Hz, 2H), 6.94 (d, J ) 8.2 Hz, 1H), 6.02 (s, 1H), 2.28 (s,
3H), 1.59 (s, 3H), 1.56 (s, 3H), 1.31 (s, 3H), 1.28 (s, 3H); 13C
NMR (125 MHz) δ (ppm) 174.4, 169.8, 169.7, 138.6, 135.7, 135.3,
133.1, 131.6, 130.2, 129.7, 129.6, 129.3, 126.8, 122.4, 118.2, 117.3,
112.2, 69.9, 69.2, 60.5, 57.6, 22.5, 21.1, 21.0, 18.5, 16.3; MS (EI)
70 (100), 153 (76), 180 (45), 547 (30)/ 549 (20). Anal. Calcd for
C30H27Cl2N3O3: C 65.70, H 4.96, N 7.66. Found: C 65.59, H 5.01,
N 7.64.
(R,S)- and (S,R)-2′-(3′′,3′′-dimethyl-1′′-methoxyphenylazeti-
din-2′′-one)oxy-3,3,5′-trimethyl-1-methoxyphenylspiro[azetidine-
4,3′-indolenine]-2-one 6cb-II: mp 211-212 °C; IR V (cm-1) 1771,
1
1589, 1513; H NMR (300 MHz) δ (ppm) 7.42 (d, J ) 9.0 Hz,
2H), 7.36 (d, J ) 7.8 Hz, 1H), 7.25 (d, J ) 7.9 Hz, 1H), 7.17 (s,
1H), 6.97 (d, J ) 9.0 Hz, 2H), 6.88 (d, J ) 9.0 Hz, 2H), 6.73 (d,
J ) 9.0 Hz, 2H), 6.58 (s, 1H), 3.80 (s, 3H), 3.73 (s, 3H), 2.38 (s,
3H), 1.39 (s, 3H), 1.38 (s, 3H), 1.32 (s, 3H), 0.76 (s, 3H); 13C
NMR (125 MHz) δ (ppm) 176.1, 169.7, 169.4, 156.8, 156.4, 149.2,
134.2, 131.0, 130.8, 130.4, 129.5, 125.9, 119.8, 119.0, 118.1, 114.5,
114.4, 87.1, 73.3, 59.1, 56.4, 55.5, 55.4, 22.1, 21.4, 20.2, 19.0, 16.1;
MS (EI) 176 (100), 187 (60), 241 (37), 539 (M+, 5%)/540 (3).
Anal. Calcd for C32H33N3O5: C 71.23, H 6.16, N 7.79. Found: C
70.76, H 6.54, N 7.72.
(R,S)- and (S,R)-1′-(3′′,3′′-dimethyl-1′′-chlorophenylazetidin-
2′′-one)-3,3,5′-trimethyl-1-chlorophenylspiro[azetidine-4,3′-in-
doline]-2,2′-dione 5db-II: mp 296-297 °C; IR V (cm-1) 1762,
1
1731, 1595, 1498; H NMR (500 MHz) δ (ppm) 7.25-7.28 (m,
(R,R)- and (S,S)-1′-(3′′,3′′-dimethyl-1′′-methoxyphenylazeti-
din-2′′-one)-5′-chloro-3,3,-dimethyl-1-methoxyphenylspiro[aze-
tidine-4,3′-indoline]-2,2′-dione 5cc-I: mp 239-240 °C; IR V
4H), 7.14 (d, J ) 8.6 Hz, 2H), 7.07 (m, 2H), 6.98 (d, J ) 8.1 Hz,
1H), 6.92 (d, J ) 8.5 Hz, 2H), 6.23 (br s, 1H), 2.27 (s, 3H), 1.61
(s, 3H), 1.51 (br s, 3H), 1.34 (s, 6H); 13C NMR (125 MHz) δ (ppm)
175.2, 169.8 (2 CO), 138.5, 135.33, 135.29, 133.1, 131.5, 130.1,
129.7, 129.6, 129.3, 126.7, 122.3, 118.2, 117.5, 112.4, 69.2, 68.6,
60.5, 57.0, 23.0, 21.0 (2 CH3), 18.4, 16.6; MS (EI) 70 (100), 153
(90), 180 (60), 547 (72)/549 (52). Anal. Calcd for C30H27Cl2N3O3:
C 65.70, H 4.96, N 7.66. Found: C 65.73, H 5.31, N 7.63.
(R,R)- and (S,S)-2′-(3′′,3′′-dimethyl-1′′-chlorophenylazetidin-
2′′-one)oxy-3,3,5′-trimethyl-1-chlorophenylspiro[azetidine-4,3′-
indolenine]-2-one 6db-I: mp 244-246 °C; IR V (cm-1) 1777, 1763,
1
(cm-1) 1763, 1733, 1513; H NMR (300 MHz) δ (ppm) 7.22-
7.29 (m, 4H), 7.02 (dd, J ) 8.7, 2.8 Hz, 3H), 6.87 (d, J ) 8.9 Hz,
2H), 6.76 (d, J ) 8.9 Hz, 2H), 5.99 (s, 1H), 3.78 (s, 3H), 3.75 (s,
3H), 1.58 (s, 3H), 1.56 (s, 3H), 1.31 (s, 3H), 1.24 (s, 3H); 13C
NMR (125 MHz) δ (ppm) 174.4, 169.3, 169.0, 156.9, 156.6, 139.9,
130.9, 130.5, 129.8, 128.9, 126.2, 125.0, 118.6, 117.4, 114.9, 114.6,
113.4, 70.1, 69.1, 60.8, 57.3, 55.5 (2 OCH3), 22.4, 21.2, 18.5, 16.3;
MS (EI) 134 (100), 149 (50), 176 (80), 559 (M+, 10%)/561(4).
Anal. Calcd for C31H30ClN3O5: C 66.48, H 5.40, N 7.50. Found:
C 66.16, H 5.37, N 7.44.
1
1581, 1497; H NMR (500 MHz) δ (ppm) 7.37 (d, J ) 7.8 Hz,
1H), 7.27 (d, J ) 7.8 Hz, 1H), 7.25 (d, J ) 8.8 Hz, 2H), 7.18 (s,
1H), 6.99 (d, J ) 8.8 Hz, 2H), 6.94 (d, J ) 8.7 Hz, 2H), 6.80 (d,
J ) 8.7 Hz, 2H), 6.02 (s, 1H), 2.39 (s, 3H), 1.58 (s, 6H), 1.45 (s,
3H), 1.40 (s, 3H); 13C NMR (125 MHz) δ (ppm) 175.0, 170.0,
169.5, 149.0, 136.0, 135.0, 134.7, 131.3, 130.1, 129.7, 129.6, 129.3,
129.1, 125.9, 120.2, 117.8, 117.5, 89.7, 73.4, 59.2, 57.1, 21.8, 21.5,
19.8, 19.7, 17.2; MS (EI) 138 (62), 144 (99), 180 (100), 269 (15),
547 (M+, 3%). Anal. Calcd for C30H27Cl2N3O3: C 65.70, H 4.96,
N 7.66. Found: C 65.76, H 5.20, N 7.44.
(R,S)- and (S,R)-1′-(3′′,3′′-dimethyl-1′′-methoxyphenylazeti-
din-2′′-one)-5′-chloro-3,3,-dimethyl-1-methoxyphenylspiro[aze-
tidine-4,3′-indoline]-2,2′-dione 5cc-II: mp 217-219 °C; IR V
1
(cm-1) 1764, 1734, 1515; H NMR (500 MHz) δ (ppm) 7.27 (s,
1H), 7.24 (d, J ) 9.0 Hz, 3H), 7.07 (d, J ) 8.5 Hz, 1H), 6.93
(d, J ) 9.0 Hz, 2H), 6.84 (d, J ) 9.0 Hz, 2H), 6.74 (d, J ) 9.0
Hz, 2H), 6.21 (br s, 1H), 3.80 (s, 3H), 3.78 (s, 3H), 1.60 (s, 3H),
1.51 (br s. 3H), 1.35 (s, 3H), 1.32 (s, 3H); 13C NMR (125 MHz) δ
(ppm) 175.0, 169.2, 169.0, 156.8, 156.6, 139.8, 130.8, 130.1, 129.9,
128.9, 126.1, 124.9, 118.9, 118.6, 117.5, 114.8, 114.5, 113.6, 69.0,
68.8, 60.7, 56.7, 55.5 (2 OCH3), 22.9, 21.1, 18.4, 16.6; MS (EI)
49 (100)/51 (55), 134 (45), 149 (75), 559 (M+, 3%). Anal. Calcd
for C31H30ClN3O5: C 66.48, H 5.40, N 7.50. Found: C 66.27, H
5.61, N 7.50.
(R,S)- and (S,R)-2′-(3′′,3′′-dimethyl-1′′-chlorophenylazetidin-
2′′-one)oxy-3,3,5′-trimethyl-1-chlorophenylspiro[azetidine-4,3′-
indolenine]-2-one 6db-II: mp 178-179 °C; IR V (cm-1) 1780,
1
1771, 1587, 1496; H NMR (500 MHz) δ (ppm) 7.45 (d, J ) 8.7
Hz, 2H), 7.38 (d, J ) 7.8 Hz, 1H), 7.32 (d, J ) 8.8 Hz, 2H),
7.27 (d, J ) 7.8 Hz, 1H), 7.17 (d, J ) 8.8 Hz, 2H), 7.15 (s, 1H),
6.96 (d, J ) 8.8 Hz, 2H), 6.62 (s, 1H), 2.39 (s, 3H), 1.41 (s, 3H),
1.39 (s, 3H), 1.32 (s, 3H), 0.79 (s, 3H); 13C NMR (125 MHz) δ
(ppm) 175.6, 170.0, 169.5, 148.9, 135.7, 134.60, 134.56, 131.3,
130.1, 129.8, 129.5, 129.3 (2 C), 125.9, 120.0, 118.6, 117.9, 86.8,
73.2, 59.5, 56.7, 22.1, 21.5, 20.2, 19.0, 16.1; MS (EI) 144 (80),
180 (100), 269 (20), 547 (M+, 15%)/549 (10). Anal. Calcd for
C30H27Cl2N3O3: C 65.70, H 4.96, N 7.66. Found: C 65.69, H 4.98,
N 7.57.
(R,R)- and (S,S)-2′-(3′′,3′′-dimethyl-1′′-methoxyphenylazeti-
din-2′′-one)oxy-5′-chloro-3,3-dimethyl-1-methoxyphenylspiro-
[azetidine-4,3′-indolenine]-2-one 6cc-I: mp 205-206 °C; IR V
(cm-1) 1764, 1584, 1514; 1H NMR (500 MHz) δ (ppm) 7.44 (d, J
) 8.2 Hz, 1H), 7.40 (d, J ) 8.2 Hz, 1H), 7.36 (s, 1H), 6.99 (d, J
) 8.8 Hz, 2H), 6.81 (dd, J ) 9.0, 2.5 Hz, 4H), 6.48 (d, J ) 8.8
Hz, 2H), 5.99 (s, 1H), 3.79 (s, 3H), 3.73 (s, 3H), 1.60 (s, 3H), 1.57
(s, 3H), 1.45 (s, 3H), 1.39 (s, 3H); 13C NMR (125 MHz) δ (ppm)
176.6, 169.1, 169.0, 156.5, 156.3, 150.1, 132.5, 130.9, 130.7, 130.3,
130.1, 125.4, 121.3, 118.0, 117.5, 114.8, 114.3, 90.4, 73.5, 59.5,
56.8, 55.4, 55.3, 21.9, 19.8, 19.7, 17.3; MS (EI) 134(73), 176 (100),
261 (65), 559 (M+, 15%)/561 (5). Anal. Calcd for C31H30ClN3O5:
C 66.48, H 5.40, N 7.50. Found: C 66.21, H 5.30, N 7.35.
(R,S)- and (S,R)-2′-(3′′,3′′-dimethyl-1′′-methoxyphenylazeti-
din-2′′-one)oxy-5′-chloro-3,3-dimethyl-1-methoxyphenylspiro-
[azetidine-4,3′-indolenine]-2-one 6cc-II: mp 206-207 °C; IR V
(R,R)- and (S,S)-1′-(3′′,3′′-dimethyl-1′′-bromophenylazetidin-
2′′-one)-3,3,5′-trimethyl-1-bromophenylspiro[azetidine-4,3′-in-
doline]-2,2′-dione 5eb-I: mp 268-269 °C; IR V (cm-1) 1772, 1725,
1
1593, 1490; H NMR (500 MHz) δ (ppm) 7.46 (d, J ) 8.4 Hz,
2H), 7.33 (d, J ) 8.4 Hz, 2H), 7.24 (d, J ) 8.4 Hz, 2H), 7.11 (s,
1H), 7.05 (d, J ) 8.7 Hz, 1H), 6.96 (d, J ) 8.8 Hz, 2H), 6.94 (d,
J ) 8.3 Hz, 1H), 6.02 (s, 1H), 2.28 (s, 3H), 1.60 (s, 3H), 1.55 (s,
3H), 1.31 (s, 3H), 1.28 (s, 3H); 13C NMR (125 MHz) δ (ppm)
174.3, 169.9, 169.7, 138.6, 136.1, 135.7, 133.2, 132.7, 132.2, 131.6,
126.8, 122.4, 118.5, 117.6, 117.4, 117.2, 112.2, 69.9, 69.1, 60.6,
57.7, 22.5, 21.1, 21.0, 18.5, 16.3; MS (EI) 70 (100), 143 (35), 197
(35)/199 (32), 635 (M+, 5%)/637 (10)/639 (5). Anal. Calcd for
C30H27N3O3Br2: C 56.53, H 4.27, N 6.59. Found: C 56.74, H 4.55,
N 6.55.
1
(cm-1) 1773, 1587, 1513; H NMR (500 MHz) δ (ppm) 7.39-
7.45 (m, 4H), 7.37 (s, 1H), 6.94 (d, J ) 9.0 Hz, 2H), 6.88 (d, J )
8.9 Hz, 2H), 6,74 (d, J ) 9.0 Hz, 2H), 6.59 (s, 1H), 3.81 (s, 3H),
3.75 (s, 3H), 1.40 (s, 3H), 1.39 (s, 3H), 1.32 (s, 3H), 0.77 (s, 3H);
13C NMR (125 MHz) δ (ppm) 177.0, 169.21, 169.16, 156.9, 156.6,
150.1, 132.3, 130.6, 130.5, 130.2, 129.3, 125.3, 121.1, 119.0, 118.1,
114.5, 114.4, 87.5, 73.4, 59.8, 56.5, 55.50, 55.48, 22.2, 20.2, 18.9,
16.1; MS (EI) 134 (53), 176 (100), 559 (M+, 30)/561 (30). Anal.
Calcd for C31H30ClN3O5: C 66.48, H 5.40, N 7.50. Found: C 66.21,
H 5.67, N 7.41.
(R,S)- and (S,R)-1′-(3′′,3′′-dimethyl-1′′-bromophenylazetidin-
2′′-one)-3,3,5′-trimethyl-1-bromophenylspiro[azetidine-4,3′-in-
doline]-2,2′-dione 5eb-II: mp 284-285 °C; IR V (cm-1) 1761,
J. Org. Chem, Vol. 71, No. 12, 2006 4425

Cheng et al.
1
1730, 1596, 1494; H NMR (500 MHz) δ (ppm) 7.42 (d, J ) 8.7
(R,R)- and (S,S)-2′-(3′′,3′′-diphenyl-1′′-chlorophenylazetidin-
2′′-one)oxy-5′-chloro-3,3-diphenyl-1-chlorophenylspiro[azetidine-
4,3′-indolenine]-2-one 6fc-I: mp 244-245 °C; IR V (cm-1) 1767,
Hz, 2H), 7.29 (d, J ) 6.8 Hz, 2H), 7.20 (d, J ) 8.7 Hz, 2H), 7.08
(m, 2H), 6.97 (d, J ) 8.4 Hz, 1H), 6.85 (d, J ) 8.5 Hz, 2H), 6.22
(br s, 1H), 2.27 (s, 3H), 1.61 (s, 3H), 1.50 (br s, 3H), 1.33 (s, 6H);
13C NMR (125 MHz) δ (ppm) 175.2, 169.8 (2 CO), 138.4, 135.8,
133.2, 132.7, 132.2, 131.5, 126.7, 122.3, 118.5, 117.8, 117.2, 112.4,
69.2, 68.6, 60.5, 57.0, 23.0, 21.0, 18.4, 16.6; MS (EI) 70 (100),
143 (65), 197 (45)/199 (45), 635 (M+, 25%)/637 (55)/639 (22).
Anal. Calcd for C30H27N3O3Br2: C 56.53, H 4.27, N 6.59. Found:
C 56.74, H 4.55, N 6.55.
1
1583, 1494; H NMR δ (ppm) 7.76 (d, J ) 8.8 Hz, 2H), 7.51 (d,
J ) 8.2 Hz, 1H), 7.43 (d, J ) 8.8 Hz, 2H), 7.35-7.40 (m, 4H),
7.24-7.32 (m, 7H), 7.17-7.18 (m, 3H), 7.13 (d, J ) 8.8 Hz, 2H),
7.10 (t, J ) 7.7 Hz, 2H), 7.05 (s, 1H), 7.02 (t, J ) 7.4 Hz, 1H),
6.73 (t, J ) 7.0 Hz, 2H), 6.68 (d, J ) 8.8 Hz, 2H), 6.41 (d, J ) 7.5
Hz, 2H), 5.88 (d, J ) 1.8 Hz, 1H); 13C NMR δ (ppm) 176.8, 165.9,
164.6, 149.1, 137.0, 136.8, 136.0, 135.3, 134.7, 134.2, 131.3, 131.0,
130.6, 130.4, 130.0, 129.3, 129.1, 128.9, 128.8, 128.5, 128.4,
128.31, 128.27, 128.2, 127.9, 127.7, 126.4, 126.3, 121.1, 119.9,
117.9, 86.1, 75.6, 74.6, 72.2; MS (APCI) 274 (100), 359 (92), 815
(M+, 1%)/816/817/818. Anal. Calcd for C49H32Cl3N3O3: C 72.02,
H 3.95, N 5.14. Found: C 71.90, H 4.07, N 5.56.
(R,R)- and (S,S)-2′-(3′′,3′′-dimethyl-1′′-bromophenylazeti-
din-2′′-one)oxy-3,3,5′-trimethyl-1-bromophenylspiro[azeti-
dine-4,3′-indolenine]-2-one 6eb-I: mp 249-250 °C; IR V (cm-1
)
1
1777, 1762, 1581, 1493; H NMR (300 MHz) δ (ppm) 7.38 (d, J
) 8.8 Hz, 2H), 7.37 (d, J ) 7.9 Hz, 1H), 7.27 (d, J ) 9.1 Hz,
1H), 7.17 (s, 1H), 7.10 (d, J ) 8.8 Hz, 2H), 6.93 (d, J ) 8.8 Hz,
2H), 6.74 (d, J ) 8.8 Hz, 2H), 6.03 (s, 1H), 2.39 (s, 3H), 1.58 (s,
6H), 1.45 (s, 3H), 1.39 (s, 3H); 13C NMR (125 MHz) δ (ppm)
175.0, 170.0, 169.5, 149.0, 136.5, 135.4, 134.7, 132.6, 132.1, 131.3,
130.1, 125.9, 120.2, 118.2, 117.8, 117.4, 117.1, 89.6, 73.4, 59.2,
57.1, 21.8, 21.5, 19.8, 19.7, 17.2; MS (EI) 144 (100), 224 (53)/
226 (55), 635 (M+, 15%)/637 (35)/639 (13). Anal. Calcd for
C30H27N3O3Br2: C 56.53, H 4.27, N 6.59. Found: C 56.22, H 4.39,
N 6.50.
(R,S)- and (S,R)-2′-(3′′,3′′-diphenyl-1′′-chlorophenylazetidin-
2′′-one)oxy-5′-chloro-3,3-diphenyl-1-chlorophenylspiro[azetidine-
4,3′-indolenine]-2-one 6fc-II: mp 200-201 °C; IR V (cm-1) 1767,
1
1617, 1596, 1493; H NMR δ (ppm) 7.40-7.44 (m, 6H), 7.37 (t,
J ) 7.1 Hz, 1H), 7.34 (t, J ) 7.4 Hz, 1H), 7.22-7.28 (m, 8H),
7.16-7.20 (m, 4H), 7.11-7.14 (m, 5H), 6.82 (d, J ) 8.8 Hz, 2H),
6.76 (d, J ) 8.8 Hz, 2H), 6.50 (d, J ) 7.7 Hz, 2H), 5.80 (d,
J ) 1.5 Hz, 1H); 13C NMR δ (ppm) 177.5, 166.2, 165.1, 149.0,
137.5, 136.9, 136.0, 134.5, 131.4, 131.12, 131.08, 130.5, 130.1,
129.2, 128.7, 128.62, 128.57, 128.5, 128.2, 128.0, 127.7, 127.2,
126.1, 125.9, 122.4, 120.7, 117.7, 85.5, 75.7, 74.8, 71.4. MS (APCI)
279 (100), 816 (M + 1, 2%)/817/818/819. Anal. Calcd for
C49H32Cl3N3O3: C 72.02, H 3.95, N 5.14. Found: C 72.02, H 3.95,
N 5.14.
(R,S)- and (S,R)-2′-(3′′,3′′-dimethyl-1′′-bromophenylazetidin-
2′′-one)oxy-3,3,5′-trimethyl-1-bromophenylspiro[azetidine-4,3′-
indolenine]-2-one 6eb-II: mp 227-228 °C; IR V (cm-1) 1786,
1
1774, 1588, 1491; H NMR (500 MHz) δ (ppm) 7.47 (d, J )
8.7 Hz, 2H), 7.40 (d, J ) 8.9 Hz, 2H), 7.37 (d, J ) 8.1 Hz, 1H),
7.32 (d, J ) 8.7 Hz, 2H), 7.27 (d, J ) 9.5 Hz, 1H), 7.15 (s, 1H),
6.90 (d, J ) 8.7 Hz, 2H), 6.61 (s, 1H), 2.39 (s, 3H), 1.41 (s, 3H),
1.39 (s, 3H), 1.32 (s, 3H), 0.80 (s, 3H); 13C NMR (125 MHz) δ
(ppm) 175.6, 170.0, 169.5, 148.9, 136.2, 135.0, 134.6, 132.2 (2
C), 131.3, 129.7, 125.9, 120.1, 119.0, 118.2, 117.7, 117.1, 86.8,
73.2, 59.5, 56.8, 22.0, 21.5, 20.2, 19.0, 16.1; MS (EI) 144 (100),
157 (45), 635 (M+, 18%)/637 (35)/639 (20). Anal. Calcd for
C30H27N3O3Br2: C 56.53, H 4.27, N 6.59. Found: C 56.59, H 4.48,
N 6.60.
(R,R)- and (S,S)-1′-(3′′,3′′-diphenyl-1′′-bromophenylazetidin-
2′′-one)-5′-chloro-3,3,-diphenyl-1-bromophenylspiro[azetidine-
4,3′-indoline]-2,2′-dione 5gc-I: mp 302-303 °C; IR V (cm-1) 1770,
1
1729, 1605, 1589, 1490; H NMR δ (ppm) 7.74 (d, J ) 7.4 Hz,
2H), 7.60 (d, J ) 7.4 Hz, 2H), 7.56 (d, J ) 8.5 Hz, 2H), 7.41-
7.48 (m, 8H), 7.36 (t, J ) 7.4 Hz, 2H), 7.28-7.29 (m, 2H), 7.23
(t, J ) 7.0 Hz, 1H), 7.11-7.15 (m, 5H), 7.06 (d, J ) 8.6 Hz, 2H),
6.92 (br, 2H), 6.88 (d, J ) 8.6 Hz, 1H), 6.74 (d, J ) 8.6 Hz, 1H),
6.71 (s, 1H), 6.06 (s, 1H); 13C NMR δ (ppm) 172.7, 166.0, 165.7,
139.1, 137.8, 135.9, 135.0, 134.3, 132.7, 132.5, 130.1, 129.2,
129.03, 128.99, 128.9, 128.5, 128.3, 128.21, 128.16, 128.09, 128.06,
126.8, 126.6, 124.4, 120.7, 119.0, 118.9, 118.8, 113.1, 80.0, 72.2,
70.0; MS (TOF) 926 (M + Na+), 942 (M + K+). Anal. Calcd for
C49H32Br2ClN3O3: C 64.95, H 3.56, N 4.64. Found: C 65.01, H
3.73, N 4.67.
(R,R)- and (S,S)-1′-(3′′,3′′-diphenyl-1′′-chlorophenylazetidin-
2′′-one)-5′-chloro-3,3,-diphenyl-1-chlorophenylspiro[azetidine-
4,3′-indoline]-2,2′-dione 5fc-I: mp 289-290 °C; IR V (cm-1) 1771,
1
1729, 1605, 1492; H NMR δ (ppm) 7.74 (d, J ) 7.4 Hz, 2H),
7.60 (d, J ) 7.4 Hz, 2H), 7.41-7.48 (m, 7H), 7.34-7.37 (m, 4H),
7.30 (d, J ) 8.8 Hz, 2H), 7.27 (t, J ) 7.4 Hz, 1H), 7.22 (t, J ) 7.4
Hz, 1H), 7.09-7.16 (m, 7H), 6.93 (br, 2H), 6.88 (dd, J ) 8.6, 2.0
Hz, 1H), 6.74 (d, J ) 8.6 Hz, 1H), 6.71 (s, 1H), 6.06 (d, J ) 1.9
Hz, 1H); 13C NMR δ (ppm) 172.7, 166.0, 165.7, 139.2, 137.8,
135.9, 134.5, 134.4, 134.1, 131.23, 131.19, 130.0, 129.8, 129.6,
129.2, 129.02, 128.97, 128.9, 128.5, 128.3, 128.19, 128.16, 128.1,
128.0, 126.8, 126.6, 124.4, 120.5, 118.7, 113.1, 103.1, 80.0, 72.3,
72.2, 70.0; MS (APCI) 279 (100), 815 (M+, 1%)/816/817/818. Anal.
Calcd for C49H32Cl3N3O3: C 72.02, H 3.95, N 5.14. Found: C
71.93, H 4.04, N 5.05.
(R,S)- and (S,R)-1′-(3′′,3′′-diphenyl-1′′-bromophenylazetidin-
2′′-one)-5′-chloro-3,3,-diphenyl-1-bromophenylspiro[azetidine-
4,3′-indoline]-2,2′-dione 5gc-II: mp 192-193 °C; IR V (cm-1
)
1767, 1752, 1741, 1591, 1491; 1H NMR δ (ppm) 7.72 (d, J ) 7.4
Hz, 2H), 7.65 (d, J ) 7.3 Hz, 2H), 7.49 (t, J ) 7.6 Hz, 2H), 7.33-
7.45 (m, 10H), 7.30 (d, J ) 7.4 Hz, 1H), 7.24-7.25 (m, 3H), 7.16-
7.18 (m, 4H), 7.03 (br s, 3H), 6.90 (dd, J ) 8.7, 1.6 Hz, 1H), 6.86
(d, J ) 8.7 Hz, 2H), 6.76 (d, J ) 8.6 Hz, 1H), 6.10 (s, 1H); 13C
NMR δ (ppm) 173.4, 165.6, 165.3, 139.3, 137.7, 136.4, 134.8,
134.7, 134.4, 132.9, 132.5, 130.2, 129.3, 129.2, 128.71, 128.66,
128.2, 128.14, 128.08, 127.3, 126.9, 126.4, 124.6, 119.4, 118.6,
118.4, 113.6, 79.0, 71.7, 71.1, 68.2; MS (TOF) 926 (M + Na+),
942 (M + K+). Anal. Calcd for C49H32Br2ClN3O3: C 64.95, H
3.56, N 4.64. Found: C 64.81, H 3.66, N 4.63.
(R,S)- and (S,R)-1′-(3′′,3′′-diphenyl-1′′-chlorophenylazetidin-
2′′-one)-5′-chloro-3,3,-diphenyl-1-chlorophenylspiro[azetidine-
4,3′-indoline]-2,2′-dione 5fc-II: mp 170-171 °C; IR V (cm-1
)
1
1764, 1738, 1597, 1493; H NMR δ (ppm) 7.72 (d, J ) 7.4 Hz,
2H), 7.64 (d, J ) 7.3 Hz, 2H), 7.44-7.50 (m, 3H), 7.41 (d, J )
7.5 Hz, 4H), 7.33-7.38 (m, 4H), 7.25-7.31 (m, 2H), 7.23 (s, 4H),
7.17 (t, J ) 7.8 Hz, 2H), 7.10 (d, J ) 8.7 Hz, 2H), 7.03 (s, 2H),
6.94 (d, J ) 8.8 Hz, 2H), 6.90 (dd, J ) 8.7, 2.0 Hz, 1H), 6.77 (d,
J ) 8.7 Hz, 1H), 6.10 (d, J ) 1.9 Hz, 1H); 13C NMR δ (ppm)
173.4, 165.6, 165.3, 139.3, 137.8, 136.4, 134.9, 134.7, 134.3, 134.0,
130.9, 130.7, 130.1, 130.0, 129.5, 129.3, 129.2, 128.72, 128.67,
128.2, 128.12, 128.06, 127.4, 126.9, 126.6, 126.4, 124.6, 120.5,
119.1, 118.7, 118.2, 113.6, 79.0, 71.7, 71.1, 68.2; MS (APCI)
282 (100), 815 (M+, 30%)/816/817/818. Anal. Calcd for
C49H32Cl3N3O3: C 72.02, H 3.95, N 5.14. Found: C 72.03, H 4.20,
N 5.21.
(R,R)- and (S,S)-2′-(3′′,3′′-diphenyl-1′′-bromophenylazetidin-
2′′-one)oxy-5′-chloro-3,3-diphenyl-1-bromophenylspiro[azetidine-
4,3′-indolenine]-2-one 6gc-I: mp 250-251 °C; IR (cm-1) 1766,
1
1583, 1492; H NMR δ (ppm) 7.70 (d, J ) 8.3 Hz, 2H), 7.58 (d,
J ) 8.4 Hz, 2H), 7.36 (d, J ) 7.8 Hz, 1H), 7.36-7.39 (m, 4H),
7.24-7.30 (m, 9H), 7.16-7.18 (m, 3H), 7.10 (t, J ) 7.7 Hz, 2H),
7.04 (s, 1H), 7.02 (t, J ) 7.5 Hz, 1H), 6.73 (t, J ) 7.1 Hz, 2H),
6.62 (d, J ) 8.8 Hz, 2H), 6.40 (d, J ) 7.4 Hz, 2H), 5.88 (d, J )
1.9 Hz, 1H); 13C NMR δ (ppm) 176.7, 165.9, 164.6, 149.1, 137.0,
136.8, 136.0, 135.7, 135.2, 134.2, 132.2, 132.0, 131.3, 131.0, 130.6,
128.9, 128.8, 128.6, 128.4, 128.31, 128.28, 128.2, 127.9, 127.7,
4426 J. Org. Chem., Vol. 71, No. 12, 2006

Spiro[azetidinone-4,3′-indolinone] DeriVatiVes
126.4, 126.3, 121.1, 120.3, 121.1, 120.3, 118.2, 118.1, 117.6, 113.2,
86.1, 75.6, 74.5, 72.3; MS (TOF) 926 (M + Na+). Anal. Calcd for
C49H32Br2ClN3O3: C 64.95, H 3.56, N 4.64. Found: C 64.88, H
3.69, N 4.67.
5′-Chloro-3,3,-dimethyl-1-methylphenylspiro[azetidine-4,3′-
indoline]-2,2′-dione 9bc: mp 194-195 °C; IR V (cm-1) 3262, 1747,
1
1621, 1516; H NMR (300 MHz) δ (ppm) 8.41 (s, 1H, NH), 7.21
(dd, J ) 8.2, 2.1 Hz, 1H), 7.19 (d, J ) 2.1 Hz, 1H), 6.92 (d, J )
8.9 Hz, 2H), 6.88 (d, J ) 9.0 Hz, 2H), 6.79 (d, J ) 8.2 Hz, 1H),
2.16 (s, 3H), 1.44 (s, 3H), 1.27 (s, 3H); 13C NMR (125 MHz) δ
(ppm) 176.3, 169.9, 139.8, 134.2, 134.1, 130.4, 129.8, 128.2, 126.3,
125.2, 116.9, 112.3, 69.6, 59.9, 21.2, 20.9, 18.1; MS (TOF-EI+):
340 (M+). Anal. Calcd for C19H17ClN2O2: C 66.96, H 5.03, N 8.22.
Found: C 66.85, H 5.23, N 8.23.
(R,S)- and (S,R)-2′-(3′′,3′′-diphenyl-1′′-bromophenylazetidin-
2′′-one)oxy-5′-chloro-3,3-diphenyl-1-bromophenylspiro[azetidine-
4,3′-indolenine]-2-one 6gc-II: mp 204-205 °C; IR (cm-1) 1768,
1618, 1594, 1491; 1H NMR δ (ppm) 7.36-7.44 (m, 10H), 7.33 (t,
J ) 7.4 Hz, 1H), 7.22-7.28 (m, 7H), 7.15-7.18 (m, 3H), 7.11-
7.12 (m, 4H), 6.95 (d, J ) 8.8 Hz, 2H), 6.70 (d, J ) 8.8 Hz, 2H),
6.49 (d, J ) 7.5 Hz, 2H), 5.79 (d, J ) 1.7 Hz, 1H); 13C NMR δ
(ppm) 177.5, 166.1, 165.1, 149.0, 137.4, 136.9, 136.0, 135.9, 134.4,
133.5, 132.4, 132.1, 131.6, 131.1, 130.5, 128.7, 128.6, 128.5, 128.2,
128.0, 127.6, 127.2, 126.1, 125.9, 122.6, 120.7, 119.0, 118.9, 117.9,
117.8, 85.4, 75.7, 74.8, 71.4; MS (APCI) 579 (100), 607 (80), 904
(M + 1, 1%)/906/908. Anal. Calcd for C49H32Br2ClN3O3: C 64.95,
H 3.56, N 4.64. Found: C 65.25, H 3.94, N 4.68.
Preparation of Spiro[azetidine-4,3′-indoline]-2,2′-dione 9bc
from Hydrolysis of 5bc and 6bc. The mixture of 5bc or 6bc (0.5
mmol) and p-toluenesulfonic acid monohydrate (5 mmol) in
chloroform or 1,1,2-trichloroethane (10 mL) was refluxed for a
period of time (see Table 3). After concentration and column
chromatography, both reactions afforded 9bc as white solid in 93-
98% yield.
3,3,-Diphenyl-1-chlorophenylspiro[azetidine-4,3′-indoline]-
2,2′-dione 9fa: mp 134-135 °C [lit.14 mp 133 °C]; IR V (cm-1
3267, 1760, 1731, 1619, 1493; H NMR (300 MHz) δ 8.14 (s,
1H), 7.66 (d, J ) 7.2 Hz, 2H), 7.17-7.34 (m, 13H), 6.93 (d, J )
7.8 Hz, 1H), 6.71 (t, J ) 7.5 Hz, 1H), 6.19 (d, J ) 7.2 Hz, 1H).
)
1
1′-Diphenylacetyl-3,3,-diphenylspiro[azetidine-4,3′-indoline]-
2,2′-dione 11: mp 205-206 °C [lit.13a mp 208-209 °C]; IR V
(cm-1) 1768, 1759, 1724, 1604, 1597, 1493; 1H NMR (300 MHz)
δ 8.38 (d, J ) 8.1 Hz, 1H), 7.39 (d, J ) 7.2 Hz, 2H), 7.02-7.37
(m, 19H), 6.95 (d, J ) 9.0 Hz, 2H), 6.82 (d, J ) 9.0 Hz, 2H), 6.77
(dt, J ) 7.5, 0.9 Hz, 1H), 6.21 (s, 1H), 6.19 (dd, J ) 7.5, 0.9 Hz,
1H).
Acknowledgment. This work was supported by the National
Natural Science Foundation of China for Distinguished Young
Scholars (No. 20525207), Program for New Century Excellent
Talents in University (No. NCET-04-0143), the Key Project of
Chinese Ministry of Education (No. 104014), and the “PCSIRT”.
We thank to the analytical center of Beijing Normal University
for their help with the spectroscopic analyses.
Preparation of Spiro[azetidine-4,3′-indoline]-2,2′-dione 9 from
1 and 3. Under nitrogen atmosphere, a mixture of oxadiazolines 1
(2 mmol) and aryl isocyanate 3 (1 mmol) was refluxed in toluene
(20 mL) for 12 h. After removal of the toluene, the residue was
mixed with p-toluenesulfonic acid monohydrate (10 mmol) and
refluxed in 1,1,2-trichloroethane (20 mL) for another 8 h. After
the solvent was evaporated under vacuum, the residue was subjected
to chromatography to afford products 9 in 68-75% yields.
Preparation of 1′-Diphenylacetyl-3,3,-diphenylspiro[azetidine-
4,3′-indoline]-2,2′-dione 11 from 9fa. Under nitrogen atmosphere,
triethylamine (1 mL) was added dropwise to a solution of 9fa (0.2
mmol) and diphenylacetyl chloride (0.4 mmol) in chloroform (5
mL). The mixture was stirred at room temperature for 0.5 h. After
removal of the triethylamine hydrochloride by filtration and
evaporation of the solvent, the residue was chromatographed to
afford 11 as a white solid in 60% yield.
Supporting Information Available: The experimental proce-
dure for preparation of 1a-g, full characterization for 1b, 1d, 1e,
1f, and 1g, 1H NMR and 13C NMR spectra of 4bc, 5, 6 (excluding
6ab-II, 6bc-II, and 6ac-II), and 9bc, as well as single-crystal data
of 5db-I, 6eb-I, and 6gc-I (CIF). This material is available free of
charge via the Internet at http://pubs.acs.org.
JO060265H
J. Org. Chem, Vol. 71, No. 12, 2006 4427