Interaction of β-lactam carbenes with 3,6-diphenyltetrazines: A five-step cascade reaction for the direct construction of indeno[2,1-b]pyrrol-2- ones

Article abstract of DOI:10.1021/jo200499u

A study of the nucleophilic addition of β-lactam carbenes to 3,6-diphenyltetrazines is reported. Instead of the formation of pyrazole derivatives like most reactions between nucleophilic or ambiphilic carbenes and 3,6-disubstituted tetrazines, β-lactam carbenes reacted with 3,6-diphenyltetrazines to produce indeno[2,1-b]pyrrol-2-ones in good yields. The reaction proceeds most probably through a five-step cascade process. This work has not only provided a one-pot operation for the efficient construction of mutisubstituted indeno[2,1-b]pyrrol-2-ones but also revealed the nucleophilicity of β-lactam carbenes.

Full text of DOI:10.1021/jo200499u

NOTE
pubs.acs.org/joc
Interaction of β-Lactam Carbenes with 3,6-Diphenyltetrazines:
A Five-Step Cascade Reaction for the Direct Construction
of Indeno[2,1-b]pyrrol-2-ones
Juan Xing, Xiao-Rong Wang, Cai-Xia Yan, and Ying Cheng*
College of Chemistry, Beijing Normal University, Beijing 100875, China
S Supporting Information
b
ABSTRACT: A study of the nucleophilic addition of β-lactam
carbenes to 3,6-diphenyltetrazines is reported. Instead of the
formation of pyrazole derivatives like most reactions between
nucleophilic or ambiphilic carbenes and 3,6-disubstituted tetra-
zines, β-lactam carbenes reacted with 3,6-diphenyltetrazines to
produce indeno[2,1-b]pyrrol-2-ones in good yields. The reac-
tion proceeds most probably through a five-step cascade
process. This work has not only provided a one-pot operation
for the efficient construction of mutisubstituted indeno[2,1-b]pyrrol-2-ones but also revealed the nucleophilicity of β-lactam
carbenes.
ucleophilic carbenes that are mainly N-heterocyclic car-
benes haveattractedcontinuedinterestfromorganicchemists
1990s.13 We have observed that β-lactam carbenes undergo both
nucleophilic reaction with aryl isocyanates and electrophilic reac-
tion with aryl isonitriles to produce spiro[azetidin-2-one-4,30-
indol-20-ones] and 2-azetidinonylidene indoles, respectively.12
Our previous works have indicated that β-lactam carbenes are
unique intermediates in the construction of novel spiro- and fused
heterocyclic compounds.12 To gain insight into the ambident
reactivity of β-lactam carbenes and to further explore their
synthetic utility, we undertook the current investigate on the
reaction of β-lactam carbenes with 3,6-diphenyl- and 3,6-bis-
(4-substituted phenyl)tetrazines. We were delighted to discover
that the reaction of β-lactam carbenes with 3,6-diphenyltetrazines
proceeded in an unprecedented five-step cascade process to
produce tricycle-fused indeno[2,1-b]pyrrol-2-ones in good yields.
We started this work with the examination of the reaction
between 3,3-dimethyl-1-(p-methoxyphenyl)-2-azetidinon-4-ylidene
2c and 3,6-diphenyltetrazine 3a. In practice, all β-lactam car-
benes 2 are generated in situ by thermolysis of spiro[β-lactam-
4,20-oxadiazolines] 1 following Warkentin’s method.13 Since the
optimal temperature for the generation of carbenes 2 from spiro-
oxadiazolines 1 is around 100ꢀ110 °C according to Warkentin’s
reports and our experience,12,13 the reaction of 2c with 3a
(2c:3a = 1.5:1) was examined at 100 °C in 1,4-dioxane, toluene
and 1,1,2-trichloroethane that were chemically inert solvents
toward carbenes. Surprisingly, instead of an envisaged pyrazole
derivative as those derived from most reactions between nucleo-
philic or ambiphilic carbenes and 3,6-disubstituted tetrazines,
the reaction of 2c with 3a produced two isomeric indeno[2,1-
b]pyrrol-2-ones 4c and 5c. It was found that the reaction in
N
because they are not only powerful ligands in the formation of
metal complexes1 but also useful organocatalysts2 and versatile
intermediates in organic synthesis.3 For decades, nucleophilic
carbenes have been developed into unique building blocks in the
construction of a variety of novel heterocyclic and carbocyclic
compounds. For example, the reaction of nucleophilic or ambi-
philic carbenes with isocyanates has been utilized to prepare
either indole-2-one4 or imidazoline-2,4-dione derivatives5 de-
pending on the structures of both reactants. Cyclization between
nucleophilic carbenes and vinyl ketenes affords a concise method
for the preparation of cyclopentenones.6 The stable dipolar
adducts derived from N-heterocyclic carbenes and aryl isothio-
cyanates are versatile synthons in the construction of multi-
functional pyrroles, thiophenes, spiro- or fused pyrroles, and
thiophenes.7 The three-component reactions of nucleophilic
carbenes with activated alkynes and carbonyl compounds are a
straightforward approach to mutisubstituted furans or fused
furan derivatives.8 Among the numerous reactions of N-hetero-
cyclic and ambiphilic carbenes, those with 3,6-disubstituted
1,2,4,5-tetrazines generally proceeded via a [4 þ 1] cycloaddition
followed by reversion of [4 þ 2] cycloaddition to produce
substituted pyrazoles or spiro- or fused pyrazoles depending on
the structures of both reactants.9 Only one exception has been
reported in which the substitution reaction of N-heterocyclic
carbenes with 3,6-bis(30,50-dimethylpyrazolyl)-1,2,4,5-tetrazines
afforded tetrazine derivatives.10
We have been interested in the chemistry of nucleophilic and
ambiphilic carbenes for years.7,11,12Our interest in N-heterocyclic
carbenes has led us to study the reactions of 2-azetidinone-4-
ylidenes, a type of β-lactam carbenes pioneered by Warkentin in
Received: March 7, 2011
Published: May 06, 2011
r
2011 American Chemical Society
4746
dx.doi.org/10.1021/jo200499u J. Org. Chem. 2011, 76, 4746–4752
|

The Journal of Organic Chemistry
NOTE
Table 1. Reaction of 3,3-Dimethyl-1-(p-methoxyphenyl)-2-
azetidinone-4-ylidene 2c and 3,6-Diphenyltetrazine 3a under
Different Conditions
Table 2. Reaction of Spiro[β-lactam-4,20-oxadiazolines] 1
and Diaryltetrazines 3 under Optimized Conditions
yield (%)
yield (%)
entry
1
X, R, R
3
Y
time (h)
4
5
entry
solvent
temp (°C)
time (h)
4c
5c
1
2
3
4
5
6
7
8
9
1a H, CH3, CH3
3a
3a
H
H
H
H
H
10
10
10
10
10
10
31a
10
10
10
24a
24
31
4a: 85 5a: 11
4b: 84 5b: 7
4c: 85 5c: 5
4d: 83 5d: 12
4e: 84
4f: 88 5f: 6b
4g: 63 5g: 4b
5h: 86
1
2
3
4
5
TCEa
100
5
12
12
10
4
9
80
78
85
70
48
3
1b CH3, CH3, CH3
dioxane
toluene
toluene
xylene
100
1c OCH3, CH3, CH3 3a
100
8
1d Cl, CH3, CH3
1e Br, CH3, CH3
1a H, CH3, CH3
1a H, CH3, CH3
1a H, CH3, CH3
1a H, CH3, CH3
3a
3a
reflux
reflux
5
4
3b CH3
3c OCH3
3d Cl
a TCE = 1,1,2-trichloroethane.
1,4-dioxane and toluene gave 78% and 80% yields of 4c, respec-
tively, along with 3% and 8% of 5c (Table 1, entries 1 and 2).
However, the use of 1,1,2-trichloroethane as solvent not only
diminished the total yields of products but also reversed the
selectivity between isomers 4c and 5c. The yield of major product
4c was slightly improved to 85% from the reaction undergoing in
refluxing toluene (Table 1, entry 4). Further elevation of reaction
temperature in xylene led to a decrease in products.
3e CF3
5i: 82
10 1c OCH3, CH3, CH3 3b CH3
4j: 88 5j: 6b
4k: 70 5k: 5b
11 1f OCH3, Et, Et
12 1g OCH3, (CH2)4
13 1h OCH3, (CH2)5
3b CH3
3b CH3
3b CH3
4l: 74
4m: 65 5m: 5b
ꢀ
a In this reaction, a small amount of tetrazine 3c or 3b was not consumed.
b The byproduct was isolated without full characterization.
The generality of the reaction was studied in refluxing toluene
using spiro[β-lactam-4,20-oxadiazolines] 1 and 3,6-bis(4-substi-
tuted phenyl)tetrazines 3, both bearing different substituents. As
summarized in Table 2, the N-aryl group of β-lactam carbenes 2
showed little effect on the reaction. All reactions of N-phenyl-, N-(4-
methylphenyl)-, N-(4-methoxyphenyl)-, N-(4-chlorophenyl)-, and
N-(4-bromophenyl)-substituted β-lactam carbenes 2aꢀe with di-
phenyltetrazine 3a proceeded equally efficiently to afford indeno-
[2,1-b]pyrrol-2-ones 4aꢀe in 83ꢀ85% yields, along with a small
amount of isomeric byproducts 5aꢀe (Table 2, entries 1ꢀ5). On
the contrary, the 3,3-alkyl substituents of carbene reactants did
influence the efficiency of reaction. For example, the reactions of
3,3-diethyl-, 3,3-cyclopentyl-, and 3,3-cyclohexyl-2-azetidinon-4-
ylidenes 2fꢀh with bis(4-tolyl)tetrazine 3b proceeded much slowly
and produced lower total yields of products 4 and 5 than the
reaction between 3,3-dimethyl-substituted carbene 2c and tetrazine
3b (Table 2, entries 10ꢀ13). The lower efficiency of the reactions
between β-lactam carbenes 2 bearing bulky alkyl groups and
diphenyltetrazines 3 can be best explained by the steric hindrance
both in the addition of a carbene to tetrazine and in the transforma-
tion of reaction intermediates (vide infra). In comparison to
carbene species that only influenced the efficiency of reactions,
the structure of tetrazine reactants 3 not only determined the
efficiency but also strongly influenced the outcomes of reactions.
For instance, although β-lactam carbene 2a reacted smoothly with
diphenyl- (3a), bis(4-methylphenyl)- (3b), bis(4-chlorophenyl)-
(3d), and bis(4-trifluoromethylphenyl)tetrazine (3e) to give pro-
ducts 4 or 5 in 82ꢀ88% yields (Table 2, entries 1, 6, 8, and 9), the
reaction of 2a with bis(4-methoxyphenyl)tetrazine 3c proceeded
much more slowly and produced product 4g in only a moderate
yield (63%) (Table 2, entry 7). On the other hand, while the
carbenes 2 reacted with tetrazines 3aꢀc substituted by phenyl,
Table 3. Isomerization of Products 4 to 5 under Different
Conditions
entry
4
reaction conditions
yield of 5 (%)
1
2
3
4
5
6
7
8
4a
4b
4c
4d
4c
4c
4g
4k
TCE, rt, 1 h
5a: 87
5b: 86
5c: 84
5d: 82
5c: 88
5c: 84
5g: 89
5k: 65
TCE, rt, 1 h
TCE, rt, 1 h
TCE, rt, 1 h
toluene, reflux, 24 h
BF3, toluene, rt, 0.5 h
BF3, toluene, rt, 0.5 h
BF3, toluene, rt, 5 h
p-tolyl, and p-anisyl to produce isomers 4 as major products
(Table 2, entries 1ꢀ7 and 10ꢀ13), the reactions of carbenes 2
with bis(p-chlorophenyl)tetrazine 3d and bis(p-triflouromethyl-
phenyl)tetrazine 3e afforded isomers 5 under similar conditions
(Table 2, entries 8 and 9). The lower reactivity of carbenes 2 to
bis(p-anisyl)tetrazine 3c was attributable to an electronic effect
because the reaction was initiated by the nucleophilic addition of
β-lactam carbenes 2 to diaryltetrazines 3 and the presence of strong
electron-donating substituents of 3 deactivated the tetrazines 3
toward nucleophiles. It is intriguing that the substituents on
tetrazines 3 strongly influenced the ratio of two isomeric products
4 and 5. Most probably, the electronic effect of substituents of
tetrazines 3 affected the speed of isomerization between products 4
and 5 (vide infra).
It was worth noting that some products 4 isomerized into their
isomers 5 when they were dissolved in 1,1,2-trichloroethane or
4747
dx.doi.org/10.1021/jo200499u |J. Org. Chem. 2011, 76, 4746–4752

The Journal of Organic Chemistry
NOTE
Scheme 1
deuterated chloroform or heated in refluxing toluene for a
prolonged time. As shown in Table 3, 4aꢀd dissolved in
trichloroethane were converted into 5aꢀd (82ꢀ87%) in 1 h at
ambient temperature, while 4c isomerized into 5c (88%) when
heated for 24 h in refluxing toluene. The isomerization of 4 to 5 at
high temperature indicated that this is a thermal rearrangement.
On the other hand, the transformation of 4aꢀ5d into 5aꢀd in
trichloroethane led us to propose that a trace amount of
hydrochloride released from the solvent might accelerate the
isomerization of 4. To validate our hypothesis, aqueous HCl,
TsOH hydrate, or HCl gas was added or bubbled into the
solution of products 4 in 1,4-dioxane or toluene. However,
instead of isomerizing into products 5, compounds 4 were
decomposed in the presence of a strong acid. A weaker Lewis
acid was then utilized to promote the transformation of 4 to 5. As
expected, in the presence of BF3, 4c, 4g, and 4k were converted
into 5c, 5g, and 5k in 65ꢀ89% yields in toluene at room
temperature (Table 3, entries 6ꢀ8). It was noted that the
isomerization of 3,3-diethyl-substituted indeno[2,1-b]pyrrol-2-
ones 4k to 5k, which was inefficient in refluxing toluene in the
absence of an catalyst, occurred more slowly and produced a
lower yield of 5k than that of the 3,3-dimethyl-substituted
analogue in the presence of BF3. Taking these results into
consideration, it is concluded that the isomerization of 4 to 5 is
an acid-catalyzed thermal rearrangement.
formation of products 4. As illustrated in Scheme 1, a [4 þ 1]
cycloaddition of β-lactam carbenes 2 with 3,6-diphenyltetrazines 3
forms the bridged compounds 6, which are converted to β-lactam-
spiropyrazoles 7 by the retro-DielsꢀAlder reaction. Under the
heating conditions, spiro-pyrazoles 7 undergo a 1,5-sigmatropic
rearrangement to produce pyrrolo[3,2-c]pyrazol-5-ones 8. De-
composition of the pyrazole ring of 8 led to the formation of
carbene intermediates 9, which undergo an intramolecular inser-
tion to the CꢀH bond of the phenyl to afford indeno[2,1-b]-
pyrrol-2-ones 4. A formal 1,3-H shift of cyclopentadienyl proton
of 4 produces more extensively conjugated isomers 5. To validate
our proposed mechanism, the isolation of reaction intermediates
was attempted. It was found that the reaction of β-lactam carbenes
2 with 3,6-diphenyltetrazines 3 initially formed two intermediates
7 and 8. They were converted into products 4 and 5 over a
prolonged time under heating. Since the yellow intermediate 7g
obtained from the reaction of carbene 2a with bis(4-methoxyphe-
nyl)tetrazine 3c was much stable than those derived from other
tetrazines, 7g was isolated and identified as 3050-bis(4-meth-
oxyphenyl)-3,3-dimethyl-1-phenylspiro[azetidine-2,40-pyrazol]-
4-one by spectroscopic data and single-crystal X-ray diffraction
analysis (see the Supporting Information). To isolate intermedi-
ates 8, the reactions of carbene 2a with diphenyltetrazine 3a,
bis(p-chlorophenyl)tetrazine 3d, and bis(p-triflouromethylphe-
nyl)tetrazine 3e were quenched in 1.5ꢀ2.5 h. Under these
conditions, intermediates 8 were isolated along with the products
4 or 5. Compound 8i derived from bis(p-triflouromethylphenyl)-
tetrazine 3e can be separated from product 5i by column
chromatography. However, 8a and 4a, or 8h and 5h, have similar
polarities that could not be separated by column chromatography.
Fortunately, 8a or 8h was precipitated from the mixture of 8a and
4a, or 8h and 5h, dissolving in petroleum ether and ethyl ether.
After structure determination by spectroscopic methods and
single-crystal X-ray diffraction analysis of 8h, compounds 8a,
8h, and 8i were confirmed to be dihydropyrrolo[3,2-c]pyrazol-5-
one derivatives (see the Supporting Information). The isolation
of product 5 rather than 4 from the reaction of carbene 2a with
bis(4-chlorophenyl)tetrazine 3d or bis(4-trifluoromethylphenyl)-
tetrazine 3e can be explained by the electronic effects of substit-
uents bearing the cyclopentadiene ring of 4. An electron-deficient
substituent can enhance the acidity of the cyclopentadienyl
proton of 4 and therefore probably promotes the 1,3-H shift of
The products 4 and 5 were fully characterized by spectro-
scopic data and microanalysis, which indicated that both 4 and 5
were the 1 þ 1 combination of a carbene 2 and a tetrazine 3 with
the loss of two N2 molecules. Since the spectroscopic data did not
allow full verification of the structures, to identify the products
beyond doubt, the structures of 4c and 5h were determined
unambiguously by single-crystal X-ray diffraction analysis (see
the Supporting Information). The isomers 4 and 5 can be easily
1
distinguished by their H NMR spectra because the signal of
cyclopentadienyl proton of 4 appeared around 5 ppm, while the
proton attached to the cyclopentadiene ring of 5 resonated at
about 4 ppm.
It was well documented that nucleophilic and ambiphilic
carbenes reacted with 3,6-disubstituted tetrazines generally via a
[4 þ 1] cycloaddition followed by reversion of a [4 þ 2]
cycloaddition to produce pyrazole derivatives.9 The current study
revealed intriguingly the formation of indeno[2,1-b]pyrrol-2-ones
4 and 5 from β-lactam carbenes 2 and 3,6-diphenyltetrazines3. On
the basis of the interaction pattern between nucleophilic carbenes
and tetrazines,9 a five-step cascade reaction was proposed for the
1
this proton. On the basis of the H NMR analysis of the reac-
tion mixture of 1a with bis(chlorophenyl)tetrazine 3d or with
bis(4-trifluoromethylphenyl)tetrazine 3e, product 4 could be
4748
dx.doi.org/10.1021/jo200499u |J. Org. Chem. 2011, 76, 4746–4752

The Journal of Organic Chemistry
NOTE
detected while the reaction proceeded only for 1ꢀ2 h. These
results support our proposed mechanism.
152.4, 148.5, 139.7, 138.1, 131.0, 129.7, 129.4, 128.5, 128.0, 127.8, 126.8,
124.9, 124.1, 118.0, 114.6, 55.6, 51.5, 46.0, 23.6, 23.1; MS (ESI) 382
(M þ 1). Anal. Calcd for C26H23NO2: C, 81.86; H, 6.08; N, 3.67.
Found: C, 81.79; H, 6.13; N, 3.62.
In summary, we have studied the nucleophilic reaction of
2-azetidinon-4-ylidenes, a type of ambiphilic β-lactam carbenes,
with 3,6-diphenyltetrazines. In contrast to other nucleophilic and
ambiphilic carbenes that reacted with 3,6-disubstituted tetrazines
to form pyrazole derivatives, β-lactam carbenes reacted with
3,6-diphenyltetrazines to produce indeno[2,1-b]pyrrol-2-ones in
good yields. The reaction proceeded most probably through a
five-step cascade process. A few methods for the syntheses of
indeno[2,1-b]pyrrole derivatives, such as the cycloaddition of
carbamoyl cyanides with 1,3-butadiynes,14a a one-pot reaction of
ninhydrin with triphenylphosphine, ammonium acetate, and
dialkyl acetylenedicarboxylates,14b the reaction of 2-bromo-1-
dicyanomethylene-3-indanone with aniline,14c have been docu-
mented in literature. However, no indeno[2,1-b]pyrrol-2-one or
substituted indeno[2,1-b]pyrrol-2-ones have been reported. This
work not only provided a simple and efficient method for the
construction of mutisubstituted indeno[2,1-b]pyrrol-2-ones but
also revealed the nucleophilic feature of β-lactam carbenes and
demonstrated their application in organic synthesis.
1-(4-Chlorophenyl)-3,3-dimethyl-8-phenyl-3,8-dihydroin-
deno[2,1-b]pyrrol-2-one (4d): 83% yield; mp 121ꢀ122 °C; IR ν
(cmꢀ1) 1721, 1712, 1620; 1H NMR (400 MHz, CD3COCD3) δ (ppm)
7.41 (dd, J = 8.8, 1.9 Hz, 2H), 7.36 (d, J = 7.4 Hz, 1H), 7.27 (dd, J = 8.8,
2.0 Hz, 2H), 7.23 (t, J = 7.5 Hz, 1H), 7.09ꢀ7.16 (m, 4H), 7.06 (dd, J =
8.1, 1.6 Hz, 2H), 7.01 (t, J = 7.5 Hz, 1H), 5.22 (s, 1H), 1.62 (s, 3H), 1.53
(s, 3H); 13C NMR (100 MHz, CD3COCD3) δ (ppm) 184.1, 151.0,
148.5, 139.1, 137.7, 135.7, 132.2, 131.6, 129.52, 129.45, 128.5, 128.1,
127.9, 126.1, 124.9, 124.6, 118.3, 51.7, 46.1, 23.6, 23.1; MS (ESI) 386
(M þ 1). Anal. Calcd for C25H20ClNO: C, 77.81; H, 5.22; N, 3.63.
Found: C, 77.68; H, 5.28; N, 3.46.
1-(4-Bromophenyl)-3,3-dimethyl-8-phenyl-3,8-dihydroin-
deno[2,1-b]pyrrol-2-one (4e): 84% yield; mp 124ꢀ126 °C; IR ν
(cmꢀ1) 1719, 1621, 1492; 1H NMR (400 MHz, CD3COCD3) δ (ppm)
7.43 (d, J = 8.8 Hz, 2H), 7.35ꢀ7.38 (m, 3H), 7.24 (t, J = 7.5 Hz, 1H),
7.06ꢀ7.16 (m, 6H), 7.02 (t, J = 7.5 Hz, 1H), 5.23 (s, 1H), 1.62 (s, 3H),
1.53 (s, 3H); 13C NMR (100 MHz, CD3COCD3) δ (ppm) 184.0, 150.9,
148.5, 139.1, 137.7, 136.2, 132.4, 132.3, 129.5, 128.5, 128.1, 127.9, 126.4,
124.9, 124.6, 119.4, 118.3, 51.7, 46.1, 23.6, 23.1; MS (EI) 429
(Mþ, 100). Anal. Calcd for C25H20BrNO: C, 69.78; H, 4.68; N, 3.25.
Found: C, 69.67; H, 4.79; N, 3.19.
’ EXPERIMENTAL SECTION
3,3,6-Trimethyl-1-phenyl-8-(p-tolyl)-3,8-dihydroindeno-
General Procedure for the Reaction of β-Lactam Carbenes
with 3,6-Diaryltetrazines. Under nitrogen atmosphere, the mixture
of spiro[β-lactam-4,20-oxadiazolines] 1 (1.5 mmol) and 3,6-diphenylte-
trazine 3a or 3,6-bis(4-substitutedphenyl)tetrazines 3bꢀe (1 mmol)
was heated in refluxing toluene (30 mL) for 10ꢀ31 h until the tetrazines
were totally consumed (Note: a small amount of tetrazine 3c or 3b was
recovered from the reactions of 1a with 3c and 1f with 3b). After
removal of the solvent under vacuum, the residue was chromatographed
on a silica gel column eluting with a mixture of petroleum ether and ethyl
acetate from 10:1 to 5:1 to give products 4 or 5. Products 4 or 5 were
further purified by recrystallization in ethyl acetate and petroleum ether.
3,3-Dimethyl-1,8-diphenyl-3,8-dihydroindeno[2,1-b]
pyrrol-2-one (4a): 85% yield; mp 106ꢀ107 °C; IR ν (cmꢀ1) 1730,
1716, 1620, 1598; 1H NMR (400 MHz, CD3COCD3) δ (ppm)
7.34ꢀ7.37 (m, 3H), 7.26 (t, J = 8.2 Hz, 2H), 7.22 (d, J = 7.6 Hz, 1H),
7.08ꢀ7.15 (m, 5H), 6.99ꢀ7.04 (m, 3H), 5.18 (s, 1H), 1.62 (s, 3H), 1.54
(s, 3H); 13C NMR (100 MHz, CD3COCD3) δ (ppm) 184.2, 151.7,
148.5, 139.4, 138.0, 136.9, 131.8, 129.4, 128.5, 128.0, 127.8, 127.0,
124.94, 124.85, 124.4, 118.2, 51.7, 46.1, 23.6, 23.2; MS (ESI) 352
(M þ 1). Anal. Calcd for C25H21NO: C, 85.44; H, 6.02; N, 3.99. Found:
C, 85.26; H, 5.91; N, 3.95.
3,3-Dimethyl-8-phenyl-1-(p-tolyl)-3,8-dihydroindeno[2,1-b]
pyrrol-2-one (4b): 84% yield; mp 140ꢀ141 °C; IR ν (cmꢀ1) 1721,
1617; 1H NMR (400 MHz, CD3COCD3) δ (ppm) 7.34 (d, J = 7.4 Hz,
1H), 7.22 (d, J = 7.5 Hz, 1H), 7.19 (d, J = 8.3 Hz, 2H), 7.09ꢀ7.15
(m, 4H), 7.00ꢀ7.07 (m, 4H), 6.99 (dt, J = 7.5, 0.9 Hz, 1H), 5.12 (s, 1H),
2.23 (s, 3H), 1.61 (s, 3H), 1.52 (s, 3H); 13C NMR (100 MHz,
CD3COCD3) δ (ppm) 184.4, 151.8, 148.5, 139.4, 138.1, 136.7, 134.3,
131.6, 130.0, 129.5, 128.5, 128.1, 127.9, 124.94, 124.89, 124.3, 118.1,
51.6, 46.1, 23.6, 23.1, 20.9; MS (ESI) 366 (M þ 1). Anal. Calcd for
C26H23NO: C, 85.45; H, 6.34; N, 3.83. Found: C, 85.27; H, 6.23;
N, 3.81.
[2,1-b]pyrrol-2-one (4f): 88% yield; mp 87ꢀ88 °C; IR ν (cmꢀ1
)
1732, 1717, 1598; 1H NMR (400 MHz, CD3COCD3) δ (ppm) 7.36 (d,
J = 7.7 Hz, 2H), 7.28ꢀ7.22 (m, 3H), 7.12 (t, J = 7.4 Hz, 1H), 7.04 (d, J =
7.6 Hz, 1H), 6.94ꢀ6.90 (m, 5H), 5.11 (s, 1H), 2.24 (s, 3H), 2.16 (s, 3H),
1.59 (s, 3H), 1.51 (s, 3H); 13C NMR (100 MHz, CD3COCD3) δ (ppm)
184.1, 150.6, 149.0, 137.1, 137.0, 136.5, 135.1, 133.8, 131.8, 130.0, 129.4,
128.4, 128.3, 126.8, 125.8, 124.6, 117.8, 51.4, 46.0, 23.7, 23.2, 21.4, 21.0;
MS (EI) 363 (90), 378 (100), 379 (Mþ, 50). Anal. Calcd for
C27H25NO: C, 85.45; H, 6.64; N, 3.69. Found: C, 85.28; H, 6.60;
N, 3.56.
6-Methoxy-8-(4-methoxyphenyl)-3,3-dimethyl-1-phenyl-
3,8-dihydroindeno[2,1-b]pyrrol-2-one (4g): 63% yield; mp
1
132ꢀ133 °C; IR ν (cmꢀ1) 1716, 1610, 1512; H NMR (400 MHz,
CD3COCD3) δ (ppm) 7.36 (d, J = 7.8 Hz, 2H), 7.27 (t, J = 8.2 Hz, 3H),
7.12 (t, J = 7.3 Hz, 1H), 6.94 (d, J = 8.6 Hz, 2H), 6.80 (dd, J = 8.1, 2.3 Hz,
1H), 6.76 (s, 1H), 6.68 (d, J = 8.6 Hz, 2H), 5.10 (s, 1H), 3.71 (s, 3H),
3.66 (s, 3H), 1.59 (s, 3H), 1.50 (s, 3H); 13C NMR (100 MHz,
CD3COCD3) δ (ppm) 184.2, 159.6, 158.2, 150.9, 149.4, 137.0, 132.1,
131.6, 129.8, 129.53, 129.45, 126.8, 124.6, 118.4, 114.8, 113.0, 112.0,
55.8, 55.4, 51.2, 46.1, 23.7, 23.2; MS (EI) 410 (100), 411 (Mþ, 85). Anal.
Calcd for C27H25NO3: C, 78.81; H, 6.12; N, 3.40. Found: C, 78.52; H,
6.07; N, 3.24.
6-Chloro-8-(4-chlorophenyl)-3,3-dimethyl-1-phenyl-3,3a-
dihydroindeno[2,1-b]pyrrol-2-one (5h): 86% yield; mp
1
202ꢀ203 °C; IR ν (cmꢀ1) 1745, 1729, 1640, 1600; H NMR (400
MHz, CDCl3) δ (ppm) 7.34 (d, J = 7.5 Hz, 1H), 7.13ꢀ7.19 (m, 7H),
7.08 (d, J = 8.5 Hz, 2H), 6.90 (d, J = 8.5 Hz, 2H), 3.93 (s, 1H), 1.72
(s, 3H), 1.00 (s, 3H); 13C NMR (100 MHz, CDCl3) δ (ppm) 182.1,
150.4, 147.7, 134.92, 134.87, 133.9, 133.1, 130.2, 129.8, 128.7, 128.0,
126.9, 124.5, 124.2, 123.7, 119.8, 115.6, 59.0, 46.9, 23.7, 20.2; MS (EI)
43 (100), 201 (90), 227 (75), 418 (65), 419 (Mþ, 55). Anal. Calcd for
C25H19Cl2NO: C, 71.44; H, 4.56; N, 3.33. Found: C, 71.36; H, 4.81;
N, 3.10.
1-(4-Methoxyphenyl)-3,3-dimethyl-8-phenyl-3,8-dihy-
droindeno[2,1-b]pyrrol-2-one (4c): 85% yield; mp 143ꢀ144 °C;
1
IR ν (cmꢀ1) 1720, 1619, 1512; H NMR (400 MHz, CD3COCD3)
3,3-Dimethyl-1-phenyl-6-(trifluoromethyl)-8-(4-(trifluoro-
methyl)phenyl)-3,3a-dihydroindeno[2,1-b]pyrrol-2-one (5i):
82% yield; mp 184ꢀ185 °C; IR ν (cmꢀ1) 1744, 1730, 1636; 1H NMR
(400 MHz, CDCl3) δ (ppm) 7.53 (d, J = 7.7 Hz, 1H), 7.46 (d, J = 7.8 Hz,
1H), 7.41 (s, 1H), 7.35 (d, J = 8.1 Hz, 2H), 7.12ꢀ7.14 (m, 3H),
δ (ppm) 7.33 (d, J = 7.4 Hz, 1H), 7.21 (dt, J = 7.5, 0.6 Hz, 1H),
7.09ꢀ7.17 (m, 6H), 7.01 (dd, J = 8.0, 1.9 Hz, 2H), 6.97 (dd, J = 7.5, 1.1
Hz, 1H), 6.79 (d, J = 9.0 Hz, 2H), 5.03 (s, 1H), 3.74 (s, 3H), 1.60 (s, 3H),
1.51 (s, 3H); 13C NMR (100 MHz, CD3COCD3) δ (ppm) 184.4, 159.0,
4749
dx.doi.org/10.1021/jo200499u |J. Org. Chem. 2011, 76, 4746–4752

The Journal of Organic Chemistry
NOTE
7.07- 7.09 (m, 4H), 4.01 (s, 1H), 1.76 (s, 3H), 1.02 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ (ppm) 182.0, 149.0, 148.7, 140.2, 135.4, 134.7,
130.9, 130.5, 130.2, 129.9, 129.8, 129.5, 129.1, 128.8, 128.7, 128.4, 128.0,
127.2, 125.7, 125.3, 124.80, 124.76, 124.7, 123.6, 123.0, 122.6, 121.0,
120.9, 120.3, 119.9, 115.8, 115.2, 59.3, 47.0, 23.7, 20.4; MS (EI) 145
(100), 487 (Mþ, 9). Anal. Calcd for C27H19F6NO: C, 66.53; H, 3.93; N,
2.87. Found: C, 66.62; H, 3.99; N, 2.86.
of time until 4 was consumed (about 0.5ꢀ5 h). After removal of solvent
under vacuum, compounds 5 were obtained by chromatography on a
silica gel column eluting with a mixture of petroleum ether and ethyl
acetate (10:1).
3,3-Dimethyl-1,8-diphenyl-3,3a-dihydroindeno[2,1-b]
pyrrol-2-one (5a): 87% yield (method A); mp 165ꢀ166 °C; IR ν
(cmꢀ1) 1735, 1721, 1643, 1596; 1H NMR (400 MHz, CDCl3) δ (ppm)
7.43 (d, J = 7.2 Hz, 1H), 7.28 (d, J = 3.2 Hz, 2H), 7.14ꢀ7.20 (m, 3H),
7.04ꢀ7.12 (m, 6H), 7.00 (dd, J = 7.6, 1.1 Hz, 2H), 3.94 (s, 1H), 1.71
(s, 3H), 0.99 (s, 3H); 13C NMR (100 MHz, CDCl3) δ (ppm) 182.4,
149.0, 145.4, 137.0, 135.3, 132.4, 128.6, 128.4, 127.64, 127.59, 126.9,
126.3, 124.3, 123.7, 123.4, 119.8, 117.8, 59.4, 46.9, 23.8, 20.1; MS (ESI)
352 (M þ 1). Anal. Calcd for C25H21NO: C, 85.44; H, 6.02; N, 3.99.
Found: C, 85.22; H, 5.98; N, 3.93.
3,3-Dimethyl-8-phenyl-1-(p-tolyl)-3,3a-dihydroindeno-
[2,1-b]pyrrol-2-one (5b): 86% yield (method A); mp 150ꢀ151 °C;
IR ν (cmꢀ1) 1730, 1627, 1595; 1H NMR (400 MHz, CDCl3) δ (ppm)
7.41 (dd, J = 7.2, 0.6 Hz, 1H), 7.27 (d, J = 3.8 Hz, 2H), 7.14ꢀ7.19 (m,
1H), 7.05ꢀ7.13 (m, 3H), 6.98ꢀ7.01 (m, 4H), 6.90 (d, J = 8.2 Hz, 2H),
3.92 (s, 1H), 2.23 (s, 3H), 1.70 (s, 3H), 0.97 (s, 3H); 13C NMR (100
MHz, CDCl3) δ (ppm) 182.6, 149.1, 145.8, 137.0, 136.2, 132.8, 132.4,
129.0, 128.7, 127.6, 126.8, 124.4, 123.6, 123.4, 119.7, 117.6, 59.4, 46.7,
23.8, 21.0, 20.2; MS (ESI) 366 (M þ 1). Anal. Calcd for C26H23NO: C,
85.45; H, 6.34; N, 3.83. Found: C, 85.34; H, 6.41; N, 3.75.
1-(4-Methoxyphenyl)-3,3,6-trimethyl-8-(p-tolyl)-3,8-dihy-
droindeno[2,1-b]pyrrol-2-one (4j): 88% yield; mp 177ꢀ178 °C;
1
IR ν (cmꢀ1) 1721, 1619, 1513; H NMR (400 MHz, CD3COCD3)
δ (ppm) 7.20 (d, J = 6.4 Hz, 1H), 7.18 (d, J = 8.9 Hz, 2H), 7.02 (d, J = 7.6
Hz, 1H), 6.95 (d, J = 8.0 Hz, 2H), 6.92 (s, 1H), 6.89 (d, J = 8.1 Hz, 2H),
6.79 (d, J = 9.0 Hz, 2H), 4.97 (s, 1H), 3.74 (s, 3H), 2.23 (s, 3H), 2.18
(s, 3H), 1.57 (s, 3H), 1.49 (s, 3H); 13C NMR (100 MHz, CD3COCD3)
δ (ppm) 184.5, 158.8, 151.2, 149.1, 137.2, 136.7, 135.2, 133.6, 131.2,
130.1, 129.8, 128.38, 128.35, 126.5, 125.9, 117.7, 114.6, 55.7, 51.1, 46.0,
23.7, 23.1, 21.4, 21.0; MS (EI) 408 (100), 409 (Mþ, 50). Anal. Calcd for
C28H27NO2: C, 82.12; H, 6.65; N, 3.42. Found: C, 82.03; H, 6.74;
N, 3.30.
3,3-Diethyl-1-(4-methoxyphenyl)-6-methyl-8-(p-tolyl)-3,8-
dihydroindeno[2,1-b]pyrrol-2-one (4k): 76% yield; mp
1
145ꢀ146 °C; IR ν (cmꢀ1) 1719, 1610, 1513; H NMR (400 MHz,
CD3COCD3) δ (ppm) 7.15 (d, J = 5.6 Hz, 1H), 7.13 (d, J = 6.9 Hz, 2H),
7.02 (d, J = 7.6 Hz, 1H), 6.95 (d, J = 8.0 Hz, 2H), 6.92 (s, 1H), 6.91 (d,
J = 8.2 Hz, 2H), 6.80 (d, J = 8.9 Hz, 2H), 5.04 (s, 1H), 3.74 (s, 3H), 2.23
(s, 3H), 2.19 (s, 3H), 2.15ꢀ1.82 (m, 4H), 0.91 (t, J = 7.4 Hz, 3H), 0.76
(t, J = 7.4 Hz, 3H); 13C NMR (100 MHz, CD3COCD3) δ (ppm) 183.5,
159.0, 154.0, 148.9, 137.3, 137.2, 135.2, 133.6, 130.0, 129.7, 128.6, 128.4,
126.9, 126.4, 125.9, 117.8, 114.7, 56.7, 55.7, 51.2, 21.4, 21.0, 10.2, 9.7; MS
(EI) 407 (100), 436 (60), 437 (Mþ, 40). Anal. Calcd for C30H31NO2: C,
82.35; H, 7.14; N, 3.20. Found: C, 82.15; H, 7.03; N, 3.06.
1-(4-Methoxyphenyl)-3,3-dimethyl-8-phenyl-3,3a-dihy-
droindeno[2,1-b]pyrrol-2-one (5c): 84% yield (method B); mp
1
173ꢀ174 °C; IR ν (cmꢀ1) 1724, 1634, 1513; H NMR (400 MHz,
CDCl3) δ (ppm) 7.42 (d, J = 7.4 Hz, 1H), 7.27 (d, J = 3.9 Hz, 2H),
7.15ꢀ7.20 (m, 1H), 7.07ꢀ7.12 (m, 3H), 7.03 (dd, J = 6.8, 2.1 Hz, 2H),
7.00 (dd, J = 7.6, 1.5 Hz, 2H), 6.64 (d, J = 9.0 Hz, 2H), 3.93 (s, 1H), 3.73
(s, 3H), 1.71 (s, 3H), 0.98 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
(ppm) 182.7, 158.0, 149.1, 146.1, 136.9, 132.4, 128.8, 128.4, 127.63,
127.55, 126.8, 125.9, 123.6, 123.4, 119.6, 117.4, 113.7, 59.4, 55.5, 46.7,
23.8, 20.2; MS (ESI) 382 (M þ 1). Anal. Calcd for C26H23NO2: C,
81.86; H, 6.08; N, 3.67. Found: C, 81.77; H, 6.18; N, 3.59.
10-(4-Methoxyphenyl)-60-methyl-80-(p-tolyl)spiro[cyclopen-
tane-1,30-indeno[2,1-b]pyrrol]-20-one (4l): 74% yield; mp
1
102ꢀ103 °C; IR ν (cmꢀ1) 1720, 1611, 1513; H NMR (400 MHz,
CD3COCD3) δ (ppm) 7.19 (d, J = 8.9 Hz, 2H), 7.11 (d, J = 7.6 Hz, 1H),
7.02 (d, J = 7.6 Hz, 1H), 6.95 (d, J = 8.0 Hz, 2H), 6.93 (s, 1H), 6.89 (d,
J = 8.0 Hz, 2H), 6.79 (d, J = 8.9 Hz, 2H), 4.97 (s, 1H), 3.74 (s, 3H), 2.23
(s, 3H), 2.19 (s, 3H), 2.12ꢀ2.02 (m, 8H); 13C NMR (100 MHz,
CD3COCD3) δ (ppm) 185.3, 158.7, 151.7, 149.2, 137.1, 136.5, 135.3,
133.5, 130.5, 130.0, 129.9, 128.4, 128.3, 126.5, 126.0, 117.7, 114.5, 55.6,
55.5, 51.0, 36.9, 36.4, 27.74, 27.68, 21.3, 21.0; MS (EI) 433 (100), 435
(Mþ, 65). Anal. Calcd for C30H29NO2: C, 82.73; H, 6.71; N, 3.22.
Found: C, 82.69; H, 6.82; N, 3.13.
1-(4-Chlorophenyl)-3,3-dimethyl-8-phenyl-3,3a-dihydroin-
deno[2,1-b]pyrrol-2-one (5d): 82% yield (method A); mp
202ꢀ203 °C; IR ν (cmꢀ1) 1725, 1638; 1H NMR (400 MHz, CDCl3)
δ (ppm) 7.43 (dd, J =7.3, 0.8 Hz, 1H), 7.28 (d, J = 4.2 Hz, 2H), 7.06 (d,
J = 9.0 Hz, 2H), 7.11 (d, J = 9.0 Hz, 2H), 7.05ꢀ7.21 (m, 4H), 7.00 (dd,
J = 6.6, 1.7 Hz, 2H), 3.92 (s, 1H), 1.71 (s, 3H), 0.97 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ (ppm) 182.3, 148.8, 144.7, 136.9, 133.8, 132.2,
131.5, 128.6, 128.5, 127.8, 127.7, 127.3, 125.3, 123.9, 123.4, 119.9, 118.3,
59.3, 46.9, 23.8, 20.1; MS (ESI) 386 (M þ 1). Anal. Calcd for
C25H20ClNO: C, 77.81; H, 5.22; N, 3.63. Found: C, 77.71; H, 5.35; N, 3.57.
3,3-Dimethyl-1-phenyl-6-methoxy-8-(p-methoxyphenyl)-
3,3a-dihydroindeno[2,1-b]pyrrol-2-one (5g): 89% yield
10-(4-Methoxyphenyl)-60-methyl-80-(p-tolyl)spiro[cyclo-
hexane-1,30-indeno[2,1-b]pyrrol]-20-one (4m): 65% yield; mp
1
142ꢀ143 °C; IR ν (cmꢀ1) 1725, 1599, 1513; H NMR (400 MHz,
CD3COCD3) δ (ppm) 7.32 (d, J = 7.7 Hz, 1H), 7.14 (d, J = 8.9 Hz, 2H),
7.04 (d, J = 7.7 Hz, 1H), 6.94 (d, J = 8.0 Hz, 2H), 6.92 (s, 1H), 6.87 (d,
J = 8.0 Hz, 2H), 6.79 (d, J = 8.9 Hz, 2H), 4.92 (s, 1H), 3.74 (s, 3H), 2.23
(s, 3H), 2.18 (s, 3H), 1.67ꢀ2.00 (m, 10H); 13C NMR (100 MHz,
CD3COCD3) δ (ppm) 182.5, 158.0, 151.6, 148.2, 136.7, 136.3, 134.4,
132.4, 129.6, 129.2, 128.8, 127.5, 127.4, 126.1, 125.0, 118.4, 113.7, 54.8,
50.5, 49.8, 32.8, 32.3, 25.0, 21.7, 21.6, 20.4, 20.1; MS (ESI) 450 (M þ 1).
Anal. Calcd for C31H31NO2: C, 82.82; H, 6.95; N, 3.12. Found: C, 82.64;
H, 6.74; N, 3.04.
1
(method B); mp 129ꢀ130 °C; IR ν (cmꢀ1) 1723, 1647, 1607; H
NMR (400 MHz, CDCl3) δ (ppm) 7.29 (d, J = 8.0 Hz, 1H), 7.05ꢀ7.16
(m, 5H), 7.90 (d, J = 8.7 Hz, 2H), 6.83 (d, J = 2.3 Hz, 1H), 6.69 (dd, J =
8.1, 2.4 Hz, 1H), 6.60 (d, J = 8.7 Hz, 2H), 3.86 (s, 1H), 3.78 (s, 3H), 3.73
(s, 3H), 1.67 (s, 3H), 0.96 (s, 3H); 13C NMR (100 MHz, CD3COCD3)
δ (ppm) 182.5, 160.9, 159.6, 151.7, 147.3, 136.7, 130.6, 130.1, 129.1,
126.8, 125.7, 125.3, 124.8, 117.8, 114.0, 109.4, 106.8, 59.2, 55.5, 47.4,
23.8, 20.2; HRMS (TOF-ESI) 412.1916 (M þ 1), 412.1913 (M þ 1).
3,3-Diethyl-1-(4-methoxyphenyl)-6-methyl-8-(p-tolyl)-3,
3a-dihydroindeno[2,1-b]pyrrol-2-one (5k): 65% yield (method B);
mp 120ꢀ121 °C; IR ν (cmꢀ1) 1723, 1641, 1596, 1512; 1H NMR (400
MHz, CD3COCD3) δ (ppm) 7.22 (d, J = 7.5 Hz, 1H), 6.92 (dd, J = 6.8, 2.1
Hz, 2H), 6.86(s, 1H), 6.82(d, J=7.5Hz, 1H), 6.79(d, J=8.0 Hz, 2H), 6.74
(d, J = 8.1 Hz, 2H), 6.55 (dt, J = 9.0, 2.1 Hz, 2H), 4.00 (s, 1H), 3.59 (s, 3H),
2.17 (s, 3H), 2.10 (s, 3H), 1.86ꢀ1.90 (m, 2H), 1.29ꢀ1.44 (m, 2H), 1.08
(t, J = 7.5 Hz, 3H), 0.59 (t, J = 7.6 Hz, 3H); 13C NMR (100 MHz,
CD3COCD3) δ (ppm) 181.2, 159.1, 150.3, 149.2, 137.5, 136.8, 135.4,
General Procedure for the Isomerization of Compounds 4
to 5. Method A. Compounds 4aꢀd (0.5 mmol) were stirred in
trichloroethane (30 mL) for 0.5ꢀ1 h at room temperature. After
removal of the solvent under vacuum, compounds 5aꢀd were isolated
by chromatography on a silica gel column eluting with a mixture of
petroleum ether and ethyl acetate (10:1).
Method B. At room temperature, the solution of Et2O BF3
3
(0.25 mmol) in toluene (5 mL) was added dropwise to compounds 4
(0.5 mmol) in toluene (30 mL), and the mixture was stirred for a period
4750
dx.doi.org/10.1021/jo200499u |J. Org. Chem. 2011, 76, 4746–4752

The Journal of Organic Chemistry
NOTE
130.9, 129.7, 129.6, 129.1, 127.3, 124.8, 124.4, 120.9, 116.4, 114.3, 55.7, 55.0,
28.2, 27.7, 21.6, 21.1, 10.0, 9.2; HRMS (TOF-ESI) 438.2429 (M þ 1),
438.2433 (M þ 1).
without full characterization, ORTEP drawing of X-ray structures
of compounds 4c, 5h, 7g, and 8h as well as single crystal data of
4c, 5h, 7g, and 8h (CIF). This material is available free of charge
via the Internet at http://pubs.acs.org.
Procedure for the Isolation of Intermediate 7g. The mixture
of spiro[β-lactam-4,20-oxadiazoline] 1a (1.5 mmol) and 3,6-bis-
(p-methoxyphenyl)tetrazine 3c (1 mmol) was heated at 100ꢀ110 °C
in toluene (30 mL) for 8 h. After removal of the solvent under vacuum,
the yellow compound 7g was isolated from the mixture of products
by chromatography on a silica gel column eluting with a mixture of
petroleum ether and ethyl acetate 3:1.
’ AUTHOR INFORMATION
Corresponding Author
*E-mail: ycheng2@bnu.edu.cn.
3050-Bis(4-methoxyphenyl)-3,3-dimethyl-1-phenylspiro-
[azetidine-2,40-pyrazol]-4-one (7g): 34% yield; mp 123ꢀ124 °C;
’ ACKNOWLEDGMENT
1
IR ν (cmꢀ1) 1769, 1606, 1507; H NMR (400 MHz, CD3COCD3)
This work was supported by the National Natural Science
Foundation of China (No. 20832006 and 20972017), Beijing
Municipal Commission of Education, and the Fundamental
Research Funds for the Central Universities (2009SC-1).
δ (ppm) 7.79 (d, J = 8.8 Hz, 4H), 7.43 (t, J = 8.0 Hz, 2H), 7.18ꢀ7.27
(m, 3H), 6.99 (d, J =9.0 Hz, 4H), 3.84 (s, 6H), 1.17 (s, 6H); 13C NMR
(100 MHz, CD3COCD3) δ (ppm) 170.1, 168.8, 163.0, 138.6, 131.1,
129.8, 126.1, 125.8, 117.4, 115.5, 81.4, 64.1, 55.8, 21.3; MS (ESI) 439
(Mþ). Anal. Calcd for C27H25N3O3: C, 73.78; H, 5.73; N, 9.56. Found:
C, 73.64; H, 5.92; N, 9.54.
Procedure for the Isolation of Intermediates 8. The mixture
of spiro[β-lactam-4,20-oxadiazoline] 1a (2 mmol) and diphenytetrazines
3a, bis(4-chlorophenyl)tetrazine 3d, or bis(4-trifluoromethylphe-
nyl)tetrazine 3e (1 mmol) was heated for 1.5ꢀ2.5 h in refluxing toluene
(30 mL) (note: 1a reacted with 3a for 1.5 h, while 1a reacted with 3d or
3e for 2.5 h). After removal of solvent under vacuum, the residue was
chromatographed on a silica gel column eluting with a mixture of
petroleum ether and ethyl acetate from 10:1 to 5:1. Compounds 8i
and product 5i were isolated in 32% and 53% yields, respectively, from
the reaction of 1a with bis(4-trifluoromethylphenyl)tetrazine 3e. How-
ever, the compounds 8a and 8h could not be separated from product 4a
and 5h, respectively, by chromatography. Finally, compound 8a, or 8h,
was precipitated from the mixture of 8a with 4a, or 8h with 5h, in
petroleum ether and ethyl ether.
3,6a-Diphenyl-6,6-dimethyl-4-phenyl-6,6a-dihydropyrrolo
[3,2-c]pyrazol-5-one (8a): mp 118ꢀ119 °C; IR ν (cmꢀ1) 1752,
1626; 1H NMR (400 MHz, CD3COCD3) δ (ppm) 7.59 (d, J = 8.7 Hz,
2H), 7.44ꢀ7.53 (m, 7H), 7.39 (t, J = 7.2 Hz, 1H), 7.32 (d, J = 7.0 Hz,
2H), 7.27 (t, J = 7.2 Hz, 1H), 7.20 (t, J = 7.0 Hz, 2H), 1.30 (s, 3H), 1.09
(s, 3H); 13C NMR (100 MHz, CD3COCD3) δ (ppm) 182.2, 156.5,
136.4, 136.0, 135.2, 130.8, 130.3, 129.7, 129.35, 129.30, 128.8, 128.7,
128.6, 125.5, 107.6, 56.0, 21.2, 20.3; HRMS (TOF-ESI) 380.1768
(M þ 1), 380.1763 (M þ 1).
’ REFERENCES
(1) Enders, D.; Niemeier, O.; Henseler, A. Chem. Rev. 2007,
107, 5606–5655.
(2) (a) Herrmann, W. A.; K€ocher, C. Angew. Chem., Int. Ed. Engl.
1997, 36, 2162–2187. (b) Bourissou, D.; Guerret, O.; Gabbai, F. P.;
Bertrand, G. Chem. Rev. 2000, 100, 39–91.
(3) Cheng, Y.; Meth-Cohn, O. Chem. Rev. 2004, 104, 2507–2530.
(4) Some examples: (a) Rigby, J. H.; Wang, Z. Org. Lett. 2002,
4, 4289–4291. (b) Rigby, J. H.; Cavezza, A.; Ahmed, G. J. Am. Chem. Soc.
1996, 118, 12848–12849. (c) Rigby, J. H.; Laurent, S. J. Org. Chem. 1999,
64, 1766–1767.
(5) Some examples: (a) Couture, P.; Terlouw, J. K.; Warkentin, J.
J. Am. Chem. Soc. 1996, 118, 4214–4215. (b) Couture, P.; Warkentin, J.
Can. J. Chem. 1997, 75, 1281–1294. (c) El-Saidi, M.; Kassam, K.; Pole,
D. L.; Tadey, T.; Warkentin, J. J. Am. Chem. Soc. 1992, 114, 8751–8752.
(6) (a) Rigby, J. H.; Wang, Z. Org. Lett. 2003, 5, 263–264. (b)
Colomvakos, J. D.; Egle, I.; Ma, J.; Pole, D. L.; Tidwell, T. T.; Warkentin,
J. J. Org. Chem. 1996, 61, 9522–9527.
(7) Some examples: (a) Cheng, Y.; Wang, B.; Wang, X.-R.; Zhang, J.-
H.; Fang, D.-C. J. Org. Chem. 2009, 74, 2357–2367. (b) Cheng, Y.; Peng,
J.-H.; Li, J.-Q. J. Org. Chem. 2010, 75, 2382–2388. (c) Cheng, Y.; Liu, M.-
F.; Fang, D.-C.; Lei, X.-M. Chem.—Eur. J. 2007, 13, 4282–4292. (d) Li, J.-
Q.; Liao, R.-Z.; Ding, W.-J.; Cheng, Y. J. Org. Chem. 2007, 72, 6266–6269.
(e) Ma, Y.-G.; Cheng, Y. Chem. Commun. 2007, 5087–5089.
(8) Some examples: (a) Nair, V.; Sreekumar, V.; Bindu, S.; Suresh, E.
Org. Lett. 2005, 7, 2297–2300. (b) Nair, V.; Bindu, S.; Sreekumar, V.;
Chiaroni, A. Org. Lett. 2002, 4, 2821–2823. (c) Nair, V.; Bindu, S.;
Sreekumar, V.; Rath, N. P. Org. Lett. 2003, 5, 665–667. (d) Nair, V.;
Deepthi, A.; Poonoth, M.; Santhamma, B. J. Org. Chem. 2006,
71, 2313–2319. (e) Ma, C.; Ding, H.; Wu, G.; Yang, Y. J. Org. Chem.
2005, 70, 8919–8923. (f) Ma, C.; Yang, Y. Org. Lett. 2005, 7, 1343–1345.
(g) Ma, C.; Ding, H.; Zhang, Y.; Bian, M. Angew. Chem., Int. Ed. 2006,
45, 7793–7797. (h) Ding, H.; Zhang, Y.; Bian, M.; Yao, W.; Ma, C. J. Org.
Chem. 2008, 73, 578–584.
3,6a-Bis(4-chlorophenyl)-6,6-dimethyl-4-phenyl-6,6a-dihy-
dropyrrolo[3,2-c]pyrazol-5-one (8h): mp 147ꢀ148 °C; IR ν
(cmꢀ1) 1758, 1656; 1H NMR (400 MHz, CD3COCD3) δ (ppm)
7.60 (d, J = 8.7 Hz, 2H), 7.47ꢀ7.59 (m, 7H), 7.29 (dd, J = 6.6, 2.0 Hz, 2H),
7.23 (dd, J = 6.8, 2.1 Hz, 2H), 1.32 (s, 3H), 1.10 (s, 3H); 13C NMR (100
MHz, CD3COCD3) δ (ppm) 182.0, 156.9, 135.9, 135.0, 134.9, 124.4,
134.1, 130.8, 130.4, 130.3, 129.8, 129.5, 129.1, 128.9, 125.8, 107.1, 56.1,
21.1, 20.2; HRMS (TOF-ESI) 448.0987 (M þ 1), 448.0983 (M þ 1).
3,6a-Bis(4-trifluoromethylphenyl)-6,6-dimethyl-4-phenyl-
6,6a-dihydropyrrolo[3,2-c]pyrazol-5-one (8i): 31% yield; mp
150ꢀ151 °C; IR ν (cmꢀ1) 1753, 1655; 1H NMR (400 MHz,
CD3COCD3) δ (ppm) 7.86 (s, 4H), 7.49ꢀ7.56 (m, 9H), 1.34
(s, 3H), 1.16 (s, 3H); 13C NMR (100 MHz, CD3COCD3) δ (ppm)
182.0, 158.5, 140.1, 135.9, 134.5, 133.9, 131.1, 130.8, 130.5, 130.2, 129.9,
129.8, 129.5, 129.4, 126.70, 126.66, 126.4, 126.3, 126.1, 125.69, 125.65,
123.7, 123.6, 107.5, 56.4, 21.2, 20.3; HRMS (TOF-ESI) 516.1506
(M þ 1), 516.1511 (M þ 1).
(9) (a) K€ummell, A.; Seitz, G. Tetrahedron Lett. 1991, 32, 2743–
2746. (b) Frenzen, G.; K€ummell, A.; Meyer-Dulheuer, C.; Seitz, G.
Chem. Ber. 1994, 127, 1803–1806. (c) Gerninghaus, C.; K€ummell, A.;
Seitz, G. Chem. Ber. 1993, 126, 733–738. (d) Imming, P.; K€ummell, A.;
Seitz, G. Heterocycles. 1993, 35, 299–304.
(10) Bostai, B.; Novak, Z.; Benyei, A. C.; Kotschy, A. Org. Lett. 2007,
9, 3437–3439.
(11) (a) Pan, H.-R.; Li, Y.-J.; Yan, C.-X.; Xing, J.; Cheng, Y. J. Org.
Chem. 2010, 75, 6644–6652. (b) Cheng, Y.; Ma, Y.-G.; Wang, X.-R.; Mo,
J.-M. J. Org. Chem. 2009, 74, 850–855. (c) Cheng, Y.; Zhu, Q.; Li, Q.-S.;
Meth-Cohn, O. J. Org. Chem. 2005, 70, 4840–4846. (d) Cheng, Y.; Yang,
H.; Meth-Cohn, O. Chem. Commun. 2003, 90–91.
’ ASSOCIATED CONTENT
(12) (a) Cheng, Y.; Cheng, L.-Q. J. Org. Chem. 2007, 72, 2625–2630.
(b) Cheng, Y.; Wang, B.; Cheng, L.-Q. J. Org. Chem. 2006, 71,
4418–4427.
Supporting Information. 1H NMR and 13C NMR spectra
S
b
of products 4, 5, 7g, 8a, 8h, and 8i excluding those byproducts
4751
dx.doi.org/10.1021/jo200499u |J. Org. Chem. 2011, 76, 4746–4752

The Journal of Organic Chemistry
NOTE
(13) (a) Zoghbi, M.; Warkentin, J. J. Org. Chem. 1991,
56, 3214–3215. (b) Zoghbi, M.; Warkentin, J. Can. J. Chem. 1993, 71,
912–918.
(14) (a) Fu, X.; Chen, J.; Li, G.; Liu, Y. Angew. Chem., Int. Ed. 2009,
48, 5500–5504. (b) Azizian, J.; Karimi, A. R.; Arefrad, H.; Mohammadi,
A. A.; Mohammadizadeh, M. R. Mol. Div. 2003, 6, 223–226. (c) Geies,
A. A. Pol. J. Chem. 1997, 71, 774–778.
4752
dx.doi.org/10.1021/jo200499u |J. Org. Chem. 2011, 76, 4746–4752