An experimental and theoretical study on the interaction of N-heterocyclic carbene-derived 1,3-dipoles with methoxycarbonylallenes: Highly regio- and stereoselective [3+2]-cycloadditions controlled by the structures of N-heterocycles of 1,3-dipoles

Article abstract of DOI:10.1021/jo802687m

The reactions of N-heterocyclic carbene-derived 1,3-dipoles with methoxycarbonylallenes were studied systematically by means of experimental and theoretical approach. The regioselectivity of [3+2]-cycloaddition of 1,3-dipoles toward the ester-substituted

Full text of DOI:10.1021/jo802687m

An Experimental and Theoretical Study on the Interaction of
N-Heterocyclic Carbene-Derived 1,3-Dipoles with
Methoxycarbonylallenes: Highly Regio- and Stereoselective
[3+2]-Cycloadditions Controlled by the Structures of N-Heterocycles
of 1,3-Dipoles
Ying Cheng,* Bo Wang, Xiao-Rong Wang, Jian-Hong Zhang, and De-Cai Fang*
College of Chemistry, Beijing Normal UniVersity, Beijing, 100875, China
ycheng2@bnu.edu.cn; dcfang@bnu.edu.cn
ReceiVed December 6, 2008
The reactions of N-heterocyclic carbene-derived 1,3-dipoles with methoxycarbonylallenes were studied
systematically by means of experimental and theoretical approach. The regioselectivity of [3+2]-
cycloaddition of 1,3-dipoles toward the ester-substituted (activated) or alkyl-substituted (less activated)
carbon-carbon double bond of methoxycarbonylallenes was strongly governed by the structures of
N-heterocycles of 1,3-dipoles. In addition, the reaction temperature played an important part in regulating
the regioselectivity of [3+2]-cycloaddition in some cases. While the reaction between benzimidazole
carbene-derived 2-thiocarbamoyl benzimidazolium inner salts 5 and methoxycarbonylallenes 6 with or
without heating gave predominantly adducts of C+-C-S- moiety to the alkyl-substituted double bond
of methoxycarbonylallenes, triazole carbene-derived triazolium salts 14 underwent mainly its [3+2]-
cycloaddition of C+-C-S- dipoles to the ester-substituted double bond of methoxycarbonylallenes. In
the case of imidazoline carbene-derived 1,3-dipoles 10, the cycloaddition occurred between the C+-C-S-
fragment and the activated double bond at room temperature, while in refluxing benzene, however, the
same reaction yielded cycloadducts from the addition of 10 to the less activated double bond of
methoxycarbonylallenes. DFT calculation revealed asynchronous cycloaddition mechanisms for the
reactions of benzimidazole and imidazoline carbene-derived 1,3-dipoles with methoxycarbonylallenes,
and a concerted mechanism for the reaction of triazole carbene-derived dipoles. The different
regioselectivity of the reaction originated from the combination of electronic and steric effects of the
reactants and the stability of the final products.
Introduction
theoretical4 chemists, because they present a number of synthetic
and mechanistic possibilities. Allenes can play either as the
three-carbon or two-carbon species in different [3+2] cycload-
ditions. In the former reactions, allenes are converted into dipolar
intermediates by the action of a nucleophilic phosphine,5 while
in the latter cases, allenes behave as dipolarophiles to cyclize
with 1,3-dipoles, using one carbon-carbon double of 1,2-
Allenes are versatile building blocks in organic synthesis,1
especially in the construction of numerous cyclic compounds
via cycloaddition reactions.2 The [3+2] cycloadditions of allenes
have attracted considerable interest from both synthetic3 and
(1) Hassan, H. H. A. M. Curr. Org. Synth. 2007, 4, 413–439.
10.1021/jo802687m CCC: $40.75
Published on Web 02/20/2009
2009 American Chemical Society
J. Org. Chem. 2009, 74, 2357–2367 2357

Cheng et al.
SCHEME 1. The Reactions between N-Heterocyclic
Carbene-Derived Ambident Dipoles and Electron-Deficient
Alkynes, Alkenes, and Ketenes
propadiene.6,7 The [3+2] cycloadditions of electron-deficient
allenes with various 1,3-dipoles such as nitrones,6a-c nitrile
oxide,6d-f aromatic N-oxides,6g-i diazoalkanes,6j,k nitrilimines,6f
and azides6f,l have been investigated. In most reactions,6 it is
the electron-deficient double bond of the allene that undergoes
the 1,3-dipolar cycloaddition reaction, since the electron-
withdrawing group lowers the LUMO energy level of allenes
which favored the dipole HOMO-dipolarophile LUMO
interaction.
Nucleophilic N-heterocyclic carbenes 1, including benzimi-
dazole, imidazoline, imidazole, triazole, and thiazole carbenes,
are known to react with aryl isothiocyanates to form the
corresponding stable zwitterionic products 2, 2-thiocarbamoyl
benzimidazolium, -imidazolinium, -imidazolium, -triazolium,
and -thiazolium inner salts, respectively.8 In 2006, we found
for the first time that the zwitterions derived from N-heterocyclic
carbenes and aryl isothiocyanates are unique ambident bis-
dipolar compounds.9a Our experimental and theoretical studies
indicated that these ambident 1,3-dipoles can act as either
C+-C-S- or C+-C-N- dipolar species toward electron-
deficient alkynes, alkenes, and ketenes to produce [3+2]
cycloadducts, spiro-thiophenes 3 or spiro-pyrroles 4 as products
or reaction intermediates (Scheme 1).9 The chem-selectivity
between C-C-S and C-C-N cycloaddition is dependent upon
both the electronic and steric effects of dipolarophiles. For
example, these ambident 1,3-dipoles acted as C+-C-S- dipoles
toward dimethyl acetylenedicarboxylate and dibenzoylacetylene
to afford spiro-thiophenes 3. On the other hand, upon treatment
with ethyl propiolate, methyl acrylate, acrylonitrile, or ketenes,
they behaved as C+-C-N- species and produced spiro-pyrrole
derivatives 4. In the cases of imidazole and thiazole carbene-
derived dipoles, the spiro-thiophene or spiro-pyrrole intermedi-
ates were not stable, being able to transform to mono or fused
thiophene or pyrrole derivatives through different ring trans-
formations.9e,f Very recently, we studied the three-component
reaction of benzimidazole carbenes, isothiocyanates, and meth-
oxycarbonylallenes.10 We found that the reaction proceeds in a
highly chem- and regioselective manner to produce predomi-
nantly spiro[benzimidazoline-2,3′-tetrahydrothiophene] deriva-
tives via a tandem nucleophilic addition of carbenes to
isothiocyanates followed by a [3+2] cycloaddition of C+-C-S-
dipolar species of 2-thiocarbamoyl benzimidazolium salts to the
less activated (electron-rich) carbon-carbon double bond of
methoxycarbonylallenes. Interestingly, the regioselectivity of this
reaction is in sharp contrast to that of most 1,3-dipolar
cycloadditions of electron-deficient allenes that are documented
in the literature.6 To gain a full understanding of the chemistry
of [3+2] cycloadditions between N-heterocyclic carbene-derived
ambident dipoles and allenes, we undertook the systematic
investigation on the reactions of 2-arylthiocarbamoyl benzimi-
dazolium, -imidazolinium, and -triazolium inner salts with
methoxycarbonylallenes by means of experimental and theoreti-
cal approaches.
(2) Murakami, M.; Matsuda, T. In Modern Allene Chemistry; Krause, N.,
Hashmi, A., Stephen, K., Eds.; Wiley-VCH Verlag GmbH & Co. KGaA:
Weinheim, Germany, 2004; Vol. 2, pp 727-815.
(3) Broggini, G.; Zecchi, G. Gazz. Chim. Ital. 1996, 126, 479–488.
(4) (a) Kavitha, K.; Venuvanalingam, P. Int. J. Quantum Chem. 2005, 104,
64–78. (b) Molteni, G.; Ponti, A. Tetrahedron 2003, 59, 5225–5229. (c) Kavitha,
K.; Venuvanalingam, P. J. Chem. Soc., Perkin Trans. 2 2002, 2130–2139. (d)
Rastelli, A.; Bagatti, M.; Gandolfi, R. Tetrahedron 1994, 50, 5561–5568.
(5) (a) Fang, Y.-Q.; Jacobsen, E. N. J. Am. Chem. Soc. 2008, 130, 5660–
5661. (b) Wilson, J. E.; Fu, G. C. Angew. Chem., Int. Ed. 2006, 45, 1426–1429.
(c) Zhu, X.-F.; Henry, C. E.; Kwon, O. Tetrahedron 2005, 61, 6276–6282.
(6) (a) Padwa, A.; Kline, D. N.; Norman, B. H. J. Org. Chem. 1989, 54,
810–817. (b) Padwa, A.; Kline, D. N.; Koehler, K. F.; Matzinger, M.;
Venkatramanan, M. K. J. Org. Chem. 1987, 52, 3909–3917. (c) Padwa, A.;
Matzinger, M.; Tomioka, Y.; Venkatramanan, M. K. J. Org. Chem. 1988, 53,
955–963. (d) Bruche, L.; Gelmi, M. L.; Zecchi, G. J. Org. Chem. 1985, 50,
3206–3208. (e) Young, D. G. J.; Zeng, D. Heterocycles 2004, 62, 121–125. (f)
Battioni, P.; Quang, L.; Quang, Y. Bull. Soc. Chim. Fr. 1978, 415–427. (g) Zhao,
B.-X.; Eguchi, S. J. Chem. Soc., Perkin Trans. 1 1997, 2973–2977. (h) Zhao,
B.-X.; Eguchi, S. Tetrahedron 1997, 53, 9575–9584. (i) Hisano, T.; Harano, K.;
Matsuoka, T.; Matsuzaki, T.; Eto, M. Chem. Pharm. Bull. 1991, 39, 537–544.
(j) Padwa, A.; Craig, S. P.; Chiacchio, U.; Kline, D. N. J. Org. Chem. 1988, 53,
2232–2238. (k) Battioni, P.; Quang, L.; Quang, Y. Bull. Soc. Chim. Fr. 1978,
401–414. (l) Khusainova, N. G.; Bredikhina, Z. A.; Sharafieva, E. S.; Pudovik,
A. N. Zh. Org. Khim 1978, 14, 2555–2558.
Results and Discussion
Experimental Study on the Reaction of N-Heterocyclic
Carbene-Derived 1,3-Dipoles with Methoxycarbonylallenes.
Having observed an unusual regioselectivity of cycloaddition
between 2-thiocarbamoyl benzimidazolium salts and methoxy-
carbonylallenes that was involved in the three-component
reaction of benzimidazole carbenes with isothiocyanates and
methoxycarbonylallenes in the presence of NaH,10 the first issue
of the current study was to investigate the effect of the neutral
reaction media on the regioselectivity. Thus, the reaction of 1,3-
dibenzyl-2-N-phenylthiocarbamoyl benzimidazolium salt 5a
with 4-benzylallenecarboxylate 6a was examined under different
conditions. It was found that the reaction conditions including
ratio of starting materials, solvent, temperature, and reaction
time affected slightly the yield of major product 7a, but did
not influence the regioselectivity. As shown in Table 1, under
all neutral reaction conditions examined, ambident dipole 5a
acted as a C+-C-S- dipolar specie selectively to cyclize with
the less activated C(2)-C(3) double bond of allene 6a giving
(7) (a) Padwa, A.; Bullock, W. H.; Kline, D. N.; Perumattam, J. J. Org.
Chem. 1989, 54, 2862–2869. (b) Hodgson, D. M.; Le Strat, F.; Avery, T. D.;
Donohue, A. C.; Brueckl, T. J. Org. Chem. 2004, 69, 8796–8803. (c) Zecchi,
G. J. Org. Chem. 1979, 44, 2796–2798.
(8) (a) Cetinkaya, B.; Cetinkaya, E.; Chamizo, J. A.; Hitchcock, P. B.; Jasim,
H. A.; Ku¨cu¨kbay, H.; Lappert, M. F. J. Chem. Soc., Perkin Trans. 1 1998, 2047–
2054. (b) Winberg, H. E.; Coffman, D. D. J. Am. Chem. Soc. 1965, 87, 2776–
2777. (c) Regitz, M.; Hocker, J.; Scho¨ssler, W.; Weber, B.; Liedhegener, A.
Liebigs Ann. Chem. 1971, 748, 1–19. (d) Schoenherr, H. J.; Wanzlick, H. W.
Chem. Ber. 1970, 103, 1037–1046. (e) Takamizawa, A.; Hirai, K.; Matsumoto,
S. Tetrahedron Lett. 1968, 9, 4027–4030. (f) Takamizawa, A.; Matsumoto, S.;
Sakai, S. Chem. Pharm. Bull. 1974, 22, 293–298.
(9) (a) Liu, M.-F.; Wang, B.; Cheng, Y. Chem. Commun. (Cambridge, U.K.)
2006, 1215–1218. (b) Cheng, Y.; Liu, M.-F.; Fang, D.-C.; Lei, X.-M. Chem.
Eur. J. 2007, 13, 4282–4292. (c) Li, J.-Q.; Liao, R.-Z.; Ding, W.-J.; Cheng, Y.
J. Org. Chem. 2007, 72, 6266–6269. (d) Zhu, Q.; Liu, M.-F.; Wang, B.; Cheng,
Y. Org. Biomol. Chem. 2007, 5, 1282–1286. (e) Ma, Y.-G.; Cheng, Y. Chem.
Commun. (Cambridge, U.K.) 2007, 5087–5089. (f) Cheng, Y.; Kang, Z.-M.;
Ma, Y.-G.; Peng, J.-H.; Liu, M.-F. Tetrahedron 2008, 64, 7362–7368.
(10) Wang, B.; Li, J.-Q.; Cheng, Y. Tetrahedron Lett. 2008, 49, 485–489.
2358 J. Org. Chem. Vol. 74, No. 6, 2009

Interaction of 1,3-Dipoles with Methoxycarbonylallenes
TABLE 1. The Reaction of 1,3-Dibenzyl-2-N-phenylthiocarbamoyl
Benzimidazolium Salt 5a with 4-Benzylallenecarboxylate 6a under
Different Conditions
SCHEME 2. The Reaction of 2-Thiocarbamoyl
Benzimidazolium Salts 5 with Methoxycarbonylallenes 6
reaction conditions
temp time
(°C) (h)
yield (%)
SCHEME 3. The Reaction of 2-Thiocarbamoyl
Imidazolinium Salts 10 with Allenes 6
starting
entry materials 5a:6a
solvent
7a 8a
1
2
3
4
5
6
7
8
9
5a, 6a
5a, 6a
5a, 6a
5a, 6a
5a, 6a
5a, 6a
5a, 6a
5a, 6a
5a, 6a
1:1
1:1
1:1
1:1
1:1.5 THF
1:1
1:1.5 benzene
1:1.5 benzene
1:1.5 benzene
acetonitrile
butanone
20-30 24
20-30 24
79
79
80
77
72
81
90
82
82
4
6
a
1,2-dichloroethane 20-30 24
1,4-dioxane 20-30 24
50-60
a
a
a
a
a
a
2
benzene
20-30 24
20-30 24
50-60
80
4
4
a No or a tiny amount of byproduct was observed.
TABLE 2. The Reaction of 2-Thiocarbamoyl Benzimidazolium
Salts 5 with Methoxycarbonylallenes 6 in Benzene
starting materials
5: R
6: R1
5a: Bn 6a: Bn
5b: p-CH3OBn 6a: Bn
reaction conditionsa
yield (%)
bond of allenes 6 was also detected in some cases (0-9%)
(Scheme 2 and Table 2, entries 8-12).
entry
temp (°C) time (h)
7
9
b
b
b
b
b
b
b
b
b
b
1
2
3
4
5
6
7
8
20-30
20-30
20-30
20-30
20-30
20-30
20-30
reflux
24
24
48
24
24
24
24
4
7a: 90
7b: 75
7c: 83
7d: 56
7e: 63
7f: 82
7g: 87
7a: 82
7b: 69
7c: 80
To examine the generality of the reaction, we then extended
the 1,3-dipolar substrates to 2-thiocarbamoyl imidazolinium salts
10. At ambient temperature in benzene, the reaction of imida-
zoline carbene-derived dipoles 10 with allenes 6 produced
imidazoline-spiro-thiophenes 11 as major products in 58-83%
yields, while the byproducts imidazoline-spiro-pyrroles 12 were
also isolated in 7-17% yields (Scheme 3; Table 3, entries 1-7).
To our surprise, in sharp contrast to the reaction of 5 that yielded
benzimidazole-spiro-thiophenes 7 from cycloaddition of dipoles
5 with the electron-rich C(2)-C(3) double bond of methoxy-
carbonylallenes 6, X-ray diffraction analysis demonstrated that
either major products 11 or minor products 12 were derived
from cycloaddition of the electron-deficient C(1)-C(2) double
bond of methoxycarbonylallenes 6 with the C+-C-S- or
C+-C-N- dipolar species of 10, respectively.
However, imidazoline-spiro-thiophenes 11 were found un-
stable under warm condition. When heated in solvent, they were
astonishingly transformed into the constitutional isomers imi-
dazoline-spiro-thiophenes 13 that were virtually the cycloadducts
of dipoles 10 with the C(2)-C(3) double bond of allenes 6.
Intrigued by this observation, we examined again the reaction
of dipoles 10 with allenes 6 in refluxing benzene. The reaction
proceeded rapidly to form spiro-thiophenes 11 initially, and
products 11 were then converted almost completely into their
isomers 13 after heating in benzene for a prolonged time
(Scheme 3; Table 3, entries 8-11).
5c: p-ClBn
5a: Bn
5a: Bn
6a: Bn
6b: Me
6c: Et
5d: Et
5e: n-Bu
5a: Bn
6a: Bn
6a: Bn
6a: Bn
9
5b: p-CH3OBn 6a: Bn
reflux
3
10
11
12
5c: p-ClBn
5a: Bn
5a: Bn
6a: Bn
6b: Me
6c: Et
reflux
2
reflux
2
7d: 70 9d: 9
b
reflux
2
7e: 82
a 5:6 ) 1:1.5. b No or a tiny amount of byproduct was observed.
the benzimidazole-spiro-thiophene 7a in high yields (72-90%).
The byproduct 8a, another spiro-thiophene yielded from cy-
cloaddition of the C+-C-S- dipole of 5a with the electron-
deficient C(1)-C(2) double bond of 6a, was isolated only in
4-6% yields from the reactions performed in acetonitrile and
in butanone (Table 1, entries 1 and 2).
The scope of the reaction was then studied under optimal
conditions by using dipoles 5 and allenes 6 that bear different
substituents. As evidenced by the results summarized in Table
2, the reaction showed tolerance for the substituent on the
reactants. At room temperature and in benzene, all reactions
proceeded smoothly to afford products 7 in 56-90% yields in
24-48 h (Scheme 2 and Table 2, entries 1-7). At an elevated
temperature such as 80-90 °C, the reactions of dipoles 5 with
allenes 6 were completed within 2-3 h to afford benzimidazole-
spiro-thiophenes 7 in 69-82% yields. A trace amount of
benzimidazole-spiro-pyrroles 9 that were derived from cycload-
dition of C+-C-N- dipoles of 5 with the C(2)-C(3) double
To further examine the effect of the structure of the
N-heterocycle on the regioselectivity, we then studied the
reaction of 2-thiocarbamoyl triazolium salts 14 with methoxy-
carbonylallenes 6 at ambient and at elevated temperatures. As
J. Org. Chem. Vol. 74, No. 6, 2009 2359

Cheng et al.
TABLE 3. The Reaction of 2-Thiocarbamoyl Imidazolinium Salts 10 with Allenes 6 in Benzene
starting materials
Ar
reaction conditionsa
temp (°C) time (h)
20-30 24
yield (%)
entry
10: R
10a: Bn
10b: p-CH3OBn
10c: p-ClBn
10d: p-ClBn
10e: p-ClBn
10a: Bn
10a: Bn
10a: Bn
10b: p-CH3OBn
10c: p-ClBn
10e: p-ClBn
6: R1
11
12
13
1
2
3
4
5
6
7
8
Ph
Ph
Ph
p-BrC6H5
3,4-Cl2C6H4
Ph
Ph
Ph
6a: Bn
6a: Bn
6a: Bn
6a: Bn
6a: Bn
6c: Et
6d: iso-Pr
6a: Bn
6a: Bn
6a: Bn
6a: Bn
11a: 75
11b: 65
11c: 63
11d: 83
11e: 60
11f: 58
11g: 63
12a: 16
12b: 12
12c: 17
12d: 11
12e: 7
12f: 17
12g: 17
12a: 16
20-30
20-30
20-30
20-30
20-30
20-30
reflux
24
24
24
24
24
24
6
13a: 74
13b: 70
13c: 71
13e: 63
9
10
11
Ph
Ph
reflux
2
12b: 14
b
reflux
reflux
12
13
b
3,4-Cl2C6H4
a 10: 6 ) 1:1.5. b Byproduct was observed without isolation.
SCHEME 4. The Reaction of 2-Thiocarbamoyl Triazolium Salts 14 with Methoxycarbonylallenes 6
TABLE 4. The Reaction of 2-Thiocarbamoyl Triazolium Salts 14 with Methoxycarbonylallenes 6
starting materials
14: Ar, AR1, Ar2
14a: Ph, Ph, Ph
yield (%)
entry
6: R1
reaction conditionsa
15-I or 17
15-II
16-I or 18
16-II
1
2
3
4
5
6
7
8
9
10
6a: Bn
6a: Bn
6a: Bn
6c: Et
benzene, rt, 24 h
benzene, rt, 15 h
benzene, rt, 23 h
benzene, rt, 24 h
benzene, rt, 15 h
toluene, reflux, 12 h
toluene, reflux, 2 h
toluene, reflux, 9 h
toluene, reflux, 7 h
toluene, reflux, 2 h
15a-I: 65
15b-I: 61
15c-I: 54
15d-I: 52
15e-I: 58
17a: 62
15a-II: 13
15b-II: 11
15c-II: 12
15d-II: 10
15e-II: 12
16a-I: 15
16b-I: 17
16c-I: 14
16d-I: 24
16e-I: 20
18a: 22
16a-II: 5
16b-II: 6
16c-II: 4
16d-II: 6
16e-II: 5
14b: Ph, p-CH3OC6H4, Ph
14c: Ph, Ph, p-CH3C6H4
14a: Ph, Ph, Ph
14a: Ph, Ph, Ph
14a: Ph, Ph, Ph
14b: Ph, p-CH3OC6H4, Ph
14c: Ph, Ph, p-CH3C6H4
14a: Ph, Ph, Ph
6d: i-Pr
6a: Bn
6a: Bn
6a: Bn
6c: Et
17b: 63
17c: 60
18b: 20
18c: 20
18d: 22
18e: 19
17d: 54
17e: 52
14a: Ph, Ph, Ph
6d: iso-Pr
a 10:6 ) 1:1.5.
illustrated in Scheme 4 and Table 4, at ambient temperature,
the reaction of 2-thiocarbamoyl-1,3,4-triaryltriazolium salts 14
with methoxycarbonylallenes 6 produced two pairs of diaster-
eomers, triazole-spiro-thiophenes 15-I and 15-II and triazole-
spiro-pyrroles 16-I and 16-II. Diastereomers 15-I and 15-II were
isolated in the yields of 52-65% and 10-13%, while 16-I and
16-II were obtained in 14-24% and 4-6% yields, respectively
(Table 4, entries 1-5). X-ray diffraction analysis indicated that
both major diastereomers 15-I and 16-I of the two pairs of
diastereomers have the (S,R) or (R,S) configurations at chiral
centers (vide infra). Similar to the 2-thiocarbamoyl imidazo-
linium salts 10, at ambient temperature, either C+-C-S- or
C+-C-N- dipolar species of triazolium salts 14 cyclized with
the electron-deficient C(1)-C(2) double bond of allenes 6 to
give 15 or 16, respectively (Scheme 4, eq 1).
Since an isomerization from imidazoline-spiro-thiophenes 11
to their constitutional isomers 13 was observed at higher
temperature (Scheme 3), the reaction between triazolium salts
14 and allenes 6 was also examined in refluxing benzene. It
was observed that the four products 15-I, 15-II, 16-I, and 16-
II formed at ambient temperature were converted into two new
compounds 17 and 18 at 80 °C. However, the transformation
2360 J. Org. Chem. Vol. 74, No. 6, 2009

Interaction of 1,3-Dipoles with Methoxycarbonylallenes
SCHEME 5. The Proposed Mechanisms for the Reactions of Dipoles 5 and 10 with Methoxycarbonylallenes 6
1
was not completed under those conditions. To promote the
transformation, the reaction temperature was increased to 110
°C. In refluxing toluene, the reaction of triazolium salts 14 with
allenes 6 finally produced products 17 and 18, via intermediates
15 and 16, in 52-63% and 19-22% yields, respectively
(Scheme 4, eq 2; Table 4, entries 6-10). Although triazole-
spiro-thiophenes 15 were similar to imidazoline-spiro-thiophenes
11 that underwent isomerization at high temperature, the
structures of products were out of our expectation. Instead of
isomerizing into the constitutional isomers 19, spiro-tetrahy-
drothiophenes 15 isomerized into spiro-dihydrothiophenes 17
under heating condition. A similar isomerization was also
observed during the transformation of spiro-tetrahydropyrroles
16 to spiro-dihydropyrroles 18. Besides the reactions of 2-thio-
carbamoyl 1,3,4-triaryltriazolium salts 14a-c with allenes 6,
we also tried the reaction between 1,3-dibenzyl-2-thiocarbamoyl
triazolium salt 14d (Ar ) Ar1 ) Bn; Ar2 ) H) and allene 6a,
but finally gave up because the products were unstable in the
processes of chromatography and recrystallization.
can be easily identified by the H NMR spectra, because the
vinyl protons of 11 were coupled with the adjacent CH2 or CH
protons to give triplet or doublet signals, respectively, while
vinyl protons of 13 have no adjacent protons and therefore
appeared as singlet signals. In addition, the isomeric triazole-
spiro-thiophenes 15 and 17, or triazole-spiro-pyrroles 16 and
18, can be differentiated by their 1H NMR spectra, because the
isomer 15 or 16 has two signals around 4-6 ppm corresponding
to the exocyclic vinyl proton and the proton of thiophene or
pyrrole ring adjacent to the ester group whereas the isomer 17
or 18 containing an endocyclic CdC bond has no signals
appearing in that region. Finally, the diastereomers 15-I and
15-II, or 16-I and 16-II, also showed a difference between their
1
thiophene or pyrrole ring protons in the H NMR spectra. The
protons of thiophene or pyrrole rings of all (S,R)- or (R,S)-15-I
or 16-I resonated at 4.8-5.0 ppm, while those ring-protons of
(R,R)- or (S,S)-15-II or 16-II appeared at slightly higher field
around 4.3-4.5 ppm.
The formation of all products can be explained by a concerted
or a stepwise [3+2] cycloaddition reaction pathway (Schemes
5 and 6). At room temperature, the ambident 1,3-dipolar
compounds 5, 10, and 14 acted predominately as the C+-C-S-
1,3-dipoles to react selectively with the C(2)-C(3) or C(1)-C(2)
double bond of methoxycarbonylallenes 6 to produce spiro-
tetrahydrothiophenes 7, 11, or 15, respectively. In turn, they
behaved as the C+-C-N- 1,3-dipolar species to add to the
C(2)-C(3) or C(1)-C(2) double bond of allenes 6 giving rise
to the byproduct, spiro-tetrahydropyrroles 9, 12, or 16. Under
heating conditions, the unstable imidazoline-spiro-thiophenes
11 underwent isomerization to give the constitutional isomers
13 via ring-opening and reclosure of the thiophene rings
(Scheme 5). The isomerization of triazole-spiro-tetrahy-
drothiophenes 15 or triazole-spiro-tetrahydropyrroles 16 took
place apparently through shifting the exocyclic carbon-carbon
double bond to the endocyclic double bond to give the
thermodynamically more stable conjugated products 17 or 18.
Since a concerted suprafacial 1,3-H shift is a symmetry-
forbidden process, the isomerization of 15 or 16 to 17 or 18
was most probably through an allyl anion intermediate 25A or
26A by deprotonation of the acidic proton adjacent to the
The structures of products were elucidated on the basis of
spectroscopic data and microanalysis. The NMR spectra, mass
data, and elemental analyses indicated all products being derived
from 1+1 addition of dipoles and allenes. To identify the
isomeric products beyond doubt, the structures of 7a, 11a, 12g,
13a, 15e-I, 16e-I, 16e-II, and 17e were determined unambigu-
ously by single-crystal X-ray diffraction analysis. Interestingly,
it was found that the exocyclic CdC bond of spiro-thiophenes
7 and 13 derived from the C(2)-C(3) double bond of allenes 6
is a Z-configuration, while the CdC bond of spiro-thiophenes
11 and 15 derived from the C(1)-C(2) double bond of 6 is a
E-configuration. It is worth noting that different types of
1
isomeric products show distinctly different 13C NMR and H
NMR spectra, and they can be used in turn as diagnostics to
differentiate isomers. First, major products spiro-thiophenes can
be differentiated from the byproduct spiro-pyrroles by using 13
C
NMR spectra, since all spiro-thiophenes 7, 11, 13, 15, and 17
gave their diagnostic CdN carbon signals around 160-170 ppm,
while CdS carbon signals of spiro-pyrroles 9, 12, 16, and 18
appeared at lower field around 190-210 ppm. Second, the
constitutional isomers imidazoline-spiro-thiophenes 11 and 13
J. Org. Chem. Vol. 74, No. 6, 2009 2361

Cheng et al.
SCHEME 6. The Proposed Mechanism for the Reaction between Dipoles 14 and Methoxycarbonylallenes 6
SCHEME 7. Computational Reactions of 2-Arylthiocarbamoyl Benzimidazolium 5d, -imidazolinium 10, and -triazolium Salt
14a with 4-Benzylallenecarboxylate 6a
carbonyl group in the presence of basic triazole compounds.
Rearrangement of 25A and 26A to 25B and 26B by shifting
the exocyclic double bond to the endocyclic double bond and
protonation of anions 25B and 26B afforded spiro-dihy-
drothiophenes 17 and spiro-dihydropyrrole 18, respectively
(Scheme 6).
and stereoselectivity in the reaction of formation of major
products spiro-thiophenes (Scheme 7).
We started the theoretical study with the reaction between
2-arylthiocarbamoyl benzimidazolium salt 5d and allene 6a. The
calculation indicated that cycloaddition of the C+-C-S- dipolar
specie of 5d with 6a could take place either at the C(2)-C(3)
or the C(1)-C(2) double bond of allene 6 to form two different
adducts 7f or 27 (see eq 1 in Scheme 7 and Figure 1). In the
former reaction, the formation of the C-S bond is much faster
than that of the C-C bond (2.168 vs. 3.303 Å in transition state
TSA1) and an intermediate INTA1 is located, therefore the
formation of 7f was via a stepwise mechanism (path A in Figure
1). In the latter case, the asynchronicity in transition state TSB1
is not as big as that in TSA1, and hence a concerted pathway
was characterized for compound 27 (path B in Figure 2).
Generally, the ester carbonyl substituted C(1)-C(2) double bond
should be more active than the benzyl substituted C(2)-C(3)
double bond toward nucleophilic additions due to the electronic
preference. However, we observed a reversed selectivity in the
reaction of benzimidazolium salts 5 with allenes 6. This unusual
regioselectivity can be well explained with our calculation
Computational Study on the Mechanism and Selectivity
of the Reaction. The chem-, regio-, and stereoselective [3+2]
cycloaddition reactions of 2-arylthiocarbamoyl benzimidazo-
lium, -imidazolinium, and -triazolium salts with methoxycar-
bonylallenes are remarkable. The most interesting and intriguing
feature of the reaction is the substrate regulated regioselectivity.
Our experimental studies have shown that it was the structure
of the heterocycle of 1,3-dipole that controlled the regioselec-
tivity. In the meantime, the reaction temperature also affected
the outcomes of the reactions. To shed light on the different
selectivities of different N-heterocyclic carbene-derived 1,3-
dipoles toward allenes, density functional theory B3LYP/6-31G*
was employed to investigate the mechanisms of the reactions.
First, the reactions between C+-C-S- dipoles and methoxy-
carbonylallenes were studied to understand the regioselectivity
2362 J. Org. Chem. Vol. 74, No. 6, 2009

Interaction of 1,3-Dipoles with Methoxycarbonylallenes
FIGURE 1. The obtained reaction pathways for 5d + 6a f 7f and 5d + 6a f 27, along with the bond lengths (Å) for the main reaction coordinates.
(Scheme 7, eq 2). Experimentally, products E-11 and 13 were
isolated respectively from the reaction of 10 with 6 at ambient
and at higher temperature. In these two reactions, the asyn-
chronicity of cycloaddition is explicit because the C-S and
C-C bonds of the thiophene ring were bonded respectively
before and after the formation of intermediate INTA2 or INTB2
(see Figure 3, paths A and B), indicating both the formation of
E-11 and 13 proceeded in two-step processes. As shown in
Figure 4, the first energy barriers for transition states TSB2 and
TSA2 are 8.44 and 14.89 kcal/mol, respectively, and the relative
free energy of TSB2 is about 3 kcal/mol lower than that of TSA2.
Therefore, the compound E-11 formed from addition of 10 to
FIGURE 2. The energy profiles (∆E and ∆G298) for the reactions of
the C(1)dC(2) bond of 6 at room temperature is a kinetically
favored product. At higher temperature, the reaction is controlled
by thermodynamic aspect. The calculation shows that product
E-11 can break the C-C bond of the thiophene ring to return
to INTB2 with an energy barrier of about 15.1 kcal/mol. Then
intermediate INTB2 is transformed into INTA2 that is easier to
form the more stable product 13 by overcoming the energy
barrier of 6 kcal/mol of TSB2-A2 (see the left column in Figure
4). The curvature of the ∆G298 profile is similar to that of ∆E
with a shift-up of about 5-18 kcal/mol (see the right column
in Figure 4). Hence, the same conclusion has been obtained
from both ∆E and ∆G298. The theoretical study has revealed
that product E-11 is the kinetically controlled product while 13
is the thermodynamically controlled one. These results can well
explain our experimental observations.
5d + 6a f 7f and 5d + 6a f 27.
results. As indicated by the energy profiles in Figure 2, TSA1 is
a little bit more stable than TSB1. The lower stability of TSB1
than TSA1 is most probably due to the repulsion between the
phenyl ring of benzimidazolium 5d and the ester carbonyl group
of 6a (see Figure 1, TSB1). That means the steric effect
counterbalances the electronic preference in the formation of
transition states. From energy profiles in Figure 2, we can
observe that the energy barrier to form INTA1 is 15.34 kcal/
mol, and the energy barrier from INTA1 to 7f in the second
step is just 0.85 kcal/mol. The energy of 7f is about 5.7 kcal/
mol lower than that for 27, which is most likely attributed to
both the conjugative stability of 7f and the steric repulsion of
27 as mentioned above. The tendency of ∆G298 is similar to
that of ∆E, and the relative free energy of product 27 at 298 K
is higher than those of the two starting materials (5d + 6a)
(see right column of Figure 2). From the ∆E and ∆G298 indicated
in Figure 2, it is clear that 7f is both a kinetically and a
thermodynamically favorable product. In addition to the regi-
oselectivity, the reaction of benzimidazolium salts 5 with allenes
6 is so highly stereoselective that only Z-7f was detected. This
stereoselectivity can be easily explained by the Molekel drawing
of structures for experimental product Z-7f and the fancy isomer
of E-7f (see Supporting Information, Figure S2). Apparently,
the reaction preferred to form Z-7f because of E-7f having a
huge steric repulsion between the carbonyl and the benzyl group
bearing to the thiophene ring.
On the contrary to the Z-configurational products 7 and 13
derived from reactions of dipoles 5 and 10 with the C(1)dC(2)
bond of allenes 6, the products 11 formed from cycloaddition
of 10 with the C(1)dC(2) bond of allenes 6 have a trans CdC
bond. This stereoselectivity was out of our expectation, because
Z-11 looked more stable than E-11 due to the repulsion between
carbonyl and alkyl group attached to the CdC bond. To clarify
the stereoselectivity, the reaction of imidazolinium 10 with 6a
to form fancy isomer Z-11 was also calculated (See Figure 3,
path C). From the energy profiles in Figure 4, it was found that
the energy and free energy of Z-11 are slight lower than those
of E-11, which means Z-11 is a litter bit more stable than E-11.
However, both ∆E and ∆G298 of TS′B2 (green line in Figure 4)
that will transform to Z-11 are higher than those of TSB2 (blue
The reaction pathways for the interaction between 2-arylth-
iocarbamoyl imidazolinium salt 10 and 6a are more complicated
J. Org. Chem. Vol. 74, No. 6, 2009 2363

Cheng et al.
FIGURE 3. The reaction pathways for 10 + 6a f E-11 and Z-11, and 10 + 6a f 13, along with the bond lengths (Å) for the main reaction
coordinates.
processes (Figure 5). Comparing the energy profiles in Figure
6 with that in Figures 2 and 4, the energy barriers of transition
states TSA3, TS′A3, and TSB3 in the reactions between triazolium
salt 14a and 6a are much higher than those energies of the
reactions between benzimidazolium salt 5d or imidazolinium
salt 10 and 6a. These results indicated that triazolium salt 14a
is less active than benzimidazolium salt 5d or imidazolinium
salt 10 toward allene 6a. The lower reactivity of 14 with 6 was
most probably due to the steric hindrance of three phenyl
substituents in the triazole ring. As shown in Figure 6, the energy
and free energy of TSA3 and TS′A3 are much lower than those
of TSB3, which indicated the formation of products 15a-I and
FIGURE 4. The energy profiles (∆E and ∆G298) for the reactions of
10 + 6a f E-11 and Z-11, and 10 + 6a f 13.
15a-II rather than 19 at room temperature was controlled by
the kinetic effect. Between the two stereoisomeric products 15-I
and 15-II, 15-I is the major product. This stereoselectivity can
be explained by the energy or free energy of transition state
TSA3, TS′A3 and product 15a-I, 15a-II (Figure 6, blue and red
line) due to the repulsion between the benzyl of allene 6a and
N-ethyl bearing to the imidazoline ring of 10 in TS′B2. Thus,
the formation of E-11 is a kinetically favored process.
lines). The lower energy or free energy of TSA3 and 15a-I than
that of TS′A3 and 15a-II demonstrated that 15a-I is both a
kinetically and thermodynamically favored product compared
to its diastereoisomers 15a-II. Although compound 19 that was
formed from the cycloaddition of dipole 14a with the C(1)dC(2)
bond of 6a is thermodynamically more stable than 15a-I and
15a-II (Figures 5 and 6), products 15a could not be converted
into 19 at higher temperature, because no intermediate that plays
Experimentally, two diastereoisomeric spiro-thiophenes 15-I
and 15-II were isolated from the cycloaddition between
C+-C-S- dipoles of 1,3,4-triaryltriazolium salts 14 with
C(1)dC(2) bonds of methoxycarbonylallenes 6 due to the
unsymmetrical structures of triazolium salts 14. The calculation
showed that no intermediate was located in the cycloadditions
of the C+-C-S-dipole of 14a with the two double bonds of
allene 6a, which means all reactions followed concerted
2364 J. Org. Chem. Vol. 74, No. 6, 2009

Interaction of 1,3-Dipoles with Methoxycarbonylallenes
FIGURE 5. The reaction pathways for 14a + 6a f 15a-I and 14a′ + 6a f 15a-II, and 14a + 6a f 19, along with the bond lengths (Å) for the
main reaction coordinates.
1,3-dipolarphiles prefer to react with the C-C-S dipolar
component, whereas the dipolarophiles with less steric hindrance
favor the reaction with the C-C-N moiety.9a–c In the current
reactions, the predominate C-C-S cycloaddition is most
probably due to the steric hindrance between the aryl group
bearing to thiocarbamoyl of dipoles 5, 10, or 14 and the two
substituents of allenes that disfavored the C-C-N pathway.
To support our supposition, the cycloaddition reactions between
the C+-C-N- dipolar species of 5d, 10, 14a, and methoxy-
carbonylallene 6a that produced the byproduct 9f, 12, or 16a-I
were calculated. The calculation indicated that all C-C-N
cycloadditions between dipoles 5d, 10, 14a, and allene 6a have
higher ∆E and ∆G than that of the corresponding C-C-S
cycloadditions. However, the spiro-pyrroles 9f, 12, and 16a-I
derived from C-C-N cycloadditions are more stable than the
C-C-S adducts spiro-thiophenes 7f, 11, and 15a-I, respectively
(see the Supporting Information, Figures S3-S8). Therefore,
it is the kinetic effects that controlled the predominate formation
of C-C-S cycloadducts.
FIGURE 6. The energy profiles (∆E and ∆G298) for the reactions of
14a + 6a f 15a-I and 14a′ + 6a f 15a-II, and 14a + 6a f 19.
a bridge for the transformation between 15a and 19 has been
located. All of the theoretical studies are in good agreement
with our experiment observations.
In addition to the high regio- and stereoselectivity, the
reactions between 2-arylthiocarbamoyl benzimidazolium, -imi-
dazolinium, and -triazolium salts with methoxycarbonylallenes
also show chemselectivity. Our experimental studies indicated
that all inner salts 5, 10, and 14 acted predominately as
C+-C-S- dipoles toward methoxycarbonylallenes to form
spiro-thiophenes products. This chemselectivity is in agreement
with our previous studies on the ambident reactivity of N-
heterocyclic carbene-derived 1,3-dipoles toward electron-
deficient alkynes, alkenes, and ketenes.9a–c We have demon-
strated that the sterically hindered and strongly electrophilic
Conclusion
In summary, we have shown that N-heterocyclic carbene-
derived 1,3-dipoles are useful reactive intermediates able to
undergo [3+2] cycloaddition reactions with methoxycarbony-
lallenes. The reaction regioselectivity, namely addition of
C+-C-S- dipoles to the ester-substituted carbon-carbon
double bond or alkyl-substituted carbon-carbon double bond
of methoxycarbonylallenes, depended on the heterocycle struc-
tures of the 1,3-dipoles. Benzimidazole carbene-derived 2-thio-
J. Org. Chem. Vol. 74, No. 6, 2009 2365

Cheng et al.
3H), 3.80 (s, 3H), 3.74 (d, J ) 15.6 Hz, 1H), 3.64 (s, 3H), 3.53 (d,
J ) 10.0 Hz, 1H), 2.88 (dd, J ) 15.9, 10.0 Hz, 1H); 13C NMR
(125 MHz, CDCl3) δ (ppm) 166.4, 164.8, 159.0, 158.9, 157.8,
150.2, 141.2, 139.8, 138.8, 130.7, 129.5, 129.2, 128.9, 128.8, 128.7,
128.4, 128.3, 128.0, 126.4, 125.4, 119.9, 118.9, 118.4, 114.3, 114.0,
113.8, 111.6, 105.3, 104.1, 98.4, 55.4, 55.3, 51.5, 50.9, 49.1, 48.8,
33.3; MS (ESI) 682 (M + 1). Anal. Calcd for C42H39N3O4S: C
73.98, H 5.77, N 6.16. Found: C 73.98, H 5.95, N 6.05.
carbamoyl benzimidazolium inner salts 5 reacted with the alkyl-
substitutedcarbon-carbondoublebondofmethoxycarbonylallenes
6 at room temperature or in refluxing benzene yielding benz-
imidazole-spiro-thiophenes 7 as the major products, whereas
triazole carbene-derived triazolium inner salts 14 underwent
[3+2] cycloaddition to the ester-substituted double bond
predominantly at room temperature to afford exoalkylidene-
substituted triazole-spiro-tetrahydrothiophene adducts 15, which
underwent exo-to-endo carbon-carbon double bond isomer-
ization to furnish triazole-spiro-dihydrothiophene 17 at higher
temperature. In some cases, the reaction temperature played an
important role in regulating the regioselectivity of [3+2]-
cycloaddition. The reaction of imidazoline carbene-derived
imidazolinium salts 10 with methoxycarbonylallenes 6 at
ambient temperature yielded almost all adducts of C+-C-S-
dipoles to the ester-substituted double bond of 6. The same
reaction performed in refluxing benzene led to the formation
of adducts of the alkyl-substituted double bond of methoxy-
carbonylallenes. Computational study with DFT (B3LYP/6-
31G*) revealed asynchronous cycloaddition mechanisms for the
reactions of benzimidazole and imidazoline carbene-derived 1,3-
dipoles, and a concerted mechanism for the reaction of triazole
carbene-derived dipoles. The unusual regioselectivity in the
reaction of benzimidazolium salts 5 with methoxycarbonylal-
lenes 6 may be due to the repulsion between the fused benzene
moiety of benzimidazolium salts 5 and the ester carbonyl group
of allenes 6 in the transition state of reaction. The kinetically
favored adducts 11 or 15 from [3+2]-cycloaddition between
imidazolinium salts 10 or triazolium salts 14 and the activated
ester-substituted double bond of methoxycarbonylallenes at
room temperature underwent transformation to products 13 or
17, respectively, at a high temperature because of the thermo-
dynamical stability of the products. The easy availability of
various of N-heterocyclic carbene-derived 1,3-dipoles and the
predictable high selectivity of the reaction toward allenes should
render the protocol valuable for the construction of complex
spiro heterocyclic compounds.
General Procedure for the Reaction of 2-Arylthiocarba-
moyl Imidazolinium Salts 10 with Methoxycarbonylallenes 6.
2-Arylthiocarbamoyl imidazolinium salts 10 (1 mmol) were mixed
with methoxycarbonylallenes 6 (1.5 mmol) in dry benzene (40 mL)
under nitrogen atmosphere. The reaction mixture was stirred at
ambient temperature (20-30 °C) for 24 h or in refluxing benzene
for 2-13 h. For the reaction at ambient temperature, solvent
benzene was evaporated under vacuum at 30-35 °C, and the
products 11 (58-83%) and 12 (7-17%) were isolated by chro-
matography on a neutral Al2O3 column eluting with a mixture of
petroleum ether (30-60 °C) and ethyl acetate (30:1) followed by
evaporating solvents at room temperature. For the reaction in
refluxing benzene, products 13 (63-74%) and 12 (11-14%) were
isolated by chromatography on a silica gel column eluting with a
mixture of petroleum ether (30-60 °C) and ethyl acetate (30:1).
(2′Z,5′E)-Methyl 1,3-dibenzyl-4′,5′-dihydro-5′-(2-phenyleth-
ylidene)-2′-(phenylimino)spiro[imidazolidine-2,3′(2′H)-thiophene]-
4′-carboxylate (11a): 430 mg, 75%, white crystals (ethyl acetate
and petroleum ether), mp 136-137 °C; IR V (cm-1) 1738, 1643,
1619, 1591; 1H NMR (500 MHz, CDCl3) δ (ppm) 7.49 (d, J ) 7.4
Hz, 2H), 7.45 (t, J ) 7.7 Hz, 2H), 7.41 (d, J ) 7.6 Hz, 2H), 7.38
(t, J ) 7.4 Hz, 2H), 7.33 (t, J ) 7.8 Hz, 2H), 7.18-7.30 (m, 6H),
7.14 (d, J ) 10.1 Hz, 2H), 7.12 (d, J ) 8.3 Hz, 2H), 5.71 (t, J )
6.4 Hz, 1H), 4.52 (d, J ) 13.6 Hz, 1H), 4.40 (s, 1H), 4.16 (d, J )
13.7 Hz, 1H), 3.86 (d, J ) 13.8 Hz, 1H), 3.80 (d, J ) 13.6 Hz,
1H), 3.72 (s, 3H), 3.40-3.47 (m, 2H), 3.21-3.25 (m, 1H),
3.08-3.13 (m, 2H), 2.90-2.93 (m, 1H); 13C NMR (125 MHz,
CDCl3) δ (ppm) 169.5, 168.1, 151.8, 139.4, 139.3, 139.0, 131.0,
129.4, 128.6, 128.5, 128.4, 128.35, 128.25, 128.2, 127.2, 126.8,
126.4, 125.0, 124.8, 120.0, 95.7, 55.4, 55.1, 53.2, 52.6, 50.6, 49.0,
35.9; MS (MALDI-TOF) 573 (M+). Anal. Calcd for C36H35N3O2S:
C 75.36, H 6.15, N 7.32. Found: C 75.27, H 6.42, N 7.23.
(E)-Methyl 1,3-dibenzyl-1′-phenyl-5′-(2-phenylethylidene)-2′-
thioxospiro[imidazolidine-2,3′-pyrrolidine]-4′-carboxylate (12a):
92 mg, 16%, yellow crystals (ethyl acetate and petroleum ether),
Experimental Section
1
mp 165-166 °C; IR V (cm-1) 1744, 1681, 1602, 1494; H NMR
(500 MHz, CDCl3) δ (ppm) 7.58 (t, J ) 7.4 Hz, 2H), 7.53 (d, J )
7.5 Hz, 2H), 7.49 (t, J ) 7.5 Hz, 1H), 7.38-7.43 (m, 4H),
7.30-7.35 (m, 4H), 7.22-7.29 (m, 4H), 7.18 (t, J ) 6.9 Hz, 1H),
7.08 (d, J ) 7.4 Hz, 2H), 4.86 (t, J ) 7.8 Hz, 1H), 4.42 (s, 1H),
4.32 (d, J ) 13.1 Hz, 1H), 4.10 (d, J ) 13.9 Hz, 1H), 3.98 (d, J )
13.9 Hz, 1H), 3.87 (d, J ) 13.1 Hz, 1H), 3.77 (s, 3H), 3.29-3.35
(m, 2H), 3.14-3.24 (m, 3H), 3.07-3.10 (m, 1H); 13C NMR (125
MHz) δ (ppm) 197.8, 169.0, 141.6, 139.5, 138.9, 138.8, 137.4,
130.1, 129.3, 128.9, 128.55, 128.48, 128.44, 128.3, 128.2, 127.2,
126.9, 126.4, 109.1, 94.8, 54.3, 52.7, 51.7, 50.2, 48.9, 33.9; MS
(MALDI-TOF) 573 (M+). Anal. Calcd for C36H35N3O2S: C 75.36,
H 6.15, N 7.32. Found: C 75.07, H 6.58, N 7.24.
General Procedure for the Reaction of 2-Arylthiocarbam-
oyl Benzimidazolium Salts 5 with Methoxycarbonylallenes 6.
2-Arylthiocarbamoyl benzimidazolium salts 5 (1 mmol) were mixed
with methoxycarbonylallenes 6 (1.5 mmol) in dry benzene (40 mL)
under nitrogen atmosphere. The reaction mixture was stirred at room
temperature (20-30 °C) for 24-48 h or at the refluxing temperature
of benzene for 2-4 h. After removal of the solvent under vacuum,
the residue was chromatographied on a silica gel column eluting
with a mixture of petroleum ether (30-60 °C) and ethyl acetate
(8:1) to afford benzimidazole-spiro-thiophenes 7 in 56-90% yields
from the reaction at room temperature (69-82% from the reaction
in refluxing benzene). In some cases, a tiny amount of byproduct
were also detected, but only benzimidazole-spiro-pyrrole 9d (9%)
was full characterized.
(Z,Z)-Methyl 2-[1,3,4′-tribenzyl-4′,5′-dihydro-2′-(phenylimino)-
spiro[imidazolidine-2,3′(2′H)-thiophen]-5′-ylidene]acetate (13a):
424 mg, 74%, white crystals (ethyl acetate and petroleum ether),
(Z,Z)-Methyl 2-[4′-benzyl-1,3,4′,5′-tetrahydro-1,3-bis(4-meth-
oxybenzyl)-2′-(phenylimino)spiro[2H-benzo[d]imidazole-2,3′(2′H)-
thiophen]-5′-ylidene]acetate (7b): 510 mg, 75%, yellow crystals
(dichloromethane and petroleum ether), mp 168-170 °C; IR V
1
mp 101-102 °C; IR V (cm-1) 1711, 1638, 1593; H NMR (400
MHz, CD3COCD3) 7.39 (d, J ) 7.4 Hz, 2H), 7.31-7.36 (m, 4H),
7.27 (d, J ) 7.6 Hz, 2H), 7.23 (d, J ) 7.8 Hz, 2H), 7.14-7.22 (m,
5H), 7.07-7.12 (m, 3H), 7.03 (dd, J ) 8.2, 1.2 Hz, 2H), 5.95 (d,
J ) 2.3 Hz, 1H), 4.36 (d, J ) 14.4 Hz, 1H), 3.99 (d, J ) 12.8 Hz,
1H), 3.90 (d, J ) 14.4 Hz, 1H), 3.78 (d, J ) 9.4 Hz, 1H), 3.73 (d,
J ) 15.8 Hz, 1H), 3.43 (d, J ) 13.0 Hz, 1H), 3.41 (s, 3H),
3.08-3.14 (m, 2H), 2.91-2.96 (m, 3H); 13C NMR (125 MHz,
CDCl3) δ (ppm) 168.0, 166.6, 161.2, 150.9, 140.8, 139.4, 138.4,
129.5, 128.9, 128.6, 128.5, 128.4, 128.2, 128.1, 127.3, 127.0, 126.3,
1
(cm-1) 1708, 1610, 1512, 1494; H NMR (500 MHz, CDCl3) δ
(ppm) 7.33-7.37 (m, 6H), 7.16-7.17 (m, 4H), 6.89 (d, J ) 8.7
Hz, 2H), 6.88 (d, J ) 8.2 Hz, 2H), 6.82 (d, J ) 8.6 Hz, 2H), 6.77
(t, J ) 3.4 Hz, 2H), 6.61 (t, J ) 7.5 Hz, 1H), 6.55 (t, J ) 7.0 Hz,
1H), 6.32 (d, J ) 7.3 Hz, 1H), 6.15 (d, J ) 7.4 Hz, 1H), 5.87 (d,
J ) 2.2 Hz, 1H), 4.82 (d, J ) 16.8 Hz, 1H), 4.54 (d, J ) 16.3 Hz,
1H), 4.46 (d, J ) 16.9 Hz, 1H), 4.42 (d, J ) 16.3 Hz, 1H), 3.84 (s,
2366 J. Org. Chem. Vol. 74, No. 6, 2009

Interaction of 1,3-Dipoles with Methoxycarbonylallenes
125.1, 120.0, 110.3, 90.9, 54.1, 53.9, 51.4, 50.1, 49.8, 48.1, 33.2;
MS (ESI): 574 (M + 1). Anal. Calcd for C36H35N3O2S: C 75.36, H
6.15, N 7.32. Found: C 75.23, H 6.31, N 7.14.
7.39 (d, J ) 8.2 Hz, 2H), 7.26-7.36 (m, 10H), 7.22 (t, J ) 6.9
Hz, 2H), 7.18 (t, J ) 7.0 Hz, 1H), 6.99-7.03 (m, 5H), 5.10 (t, J
) 7.6 Hz, 1H), 4.43 (s, 1H), 3.77 (s, 3H), 3.40 (dd, J ) 16.7, 6.9
Hz, 1H), 3.16 (dd, J ) 16.4, 8.2 Hz, 1H); 13C NMR (125 MHz) δ
(ppm) 193.1, 168.1, 149.9, 143.6, 139.4, 139.3, 137.9, 137.3, 130.2,
129.5, 129.3, 128.5, 128.3, 128.2, 127.7, 127.2, 126.3, 122.4, 119.3,
111.6, 99.0, 52.9, 51.3, 33.9; MS (-c ESI) 619 (M - 1). Anal.
Calcd for C39H32N4O2S: C 75.46, H 5.20, N 9.03. Found: C 75.16,
H 5.42, N 8.78.
General Procedure for the Reaction of 2-Arylthiocarba-
moyl Triazolium Salts 14 with Methoxycarbonylallenes 6.
2-Arylthiocarbamoyl triazolium salts 14 (2 mmol) were mixed with
methoxycarbonylallenes 6 (3 mmol) in dry benzene or toluene (60
mL) under nitrogen atmosphere. The reaction mixture in benzene
was stirred at ambient temperature (20-30 °C) for 15-24 h or in
refluxing toluene for 2-12 h. For the reaction at ambient temper-
ature, solvent benzene was evaporated under vacuum at 30-35 °C,
and the products 15-I (52-65%), 15-II (10-13%) and 16-I
(14-24%), 16-II (4-6%) were isolated by chromatography on a
silica gel column eluting with a mixture of petroleum ether (30-60
°C) and ethyl acetate (15:1) followed by evaporating solvents at
room temperature. For the reaction in refluxing toluene, products
17 (52-63%) and 18 (19-22%) were isolated by chromatography
on a silica gel column eluting with a mixture of petroleum ether
(30-60 °C) and ethyl acetate (15:1).
(Z)-Methyl
1,4-dihydro-5′-phenethyl-1,3,4-triphenyl-2′-
(phenylimino)spiro[3H-1,2,4-triazole-5,3′(2′H)-thiophene]-4′-car-
boxylate (17a): 384 mg, 62%, red crystals, mp 110-111 °C; IR V
(cm-1) 1699, 1641, 1593, 1493; 1H NMR (500 MHz) δ (ppm) 7.54
(d, J ) 6.7 Hz, 2H), 7.22-7.32 (m, 15H), 7.11-7.13 (m, 3H),
7.04 (d, J ) 6.5 Hz, 2H), 6.88 (t, J ) 6.7 Hz, 1H), 6.50 (d, J ) 7.3
Hz, 2H), 3.72 (s, 3H), 3.21-3.27 (m, 2H), 2.82 (t, J ) 7.8 Hz,
2H); 13C NMR (125 MHz) δ (ppm) 166.6, 162.4, 159.8, 151.2,
147.3, 143.0, 140.0, 138.6, 129.6, 129.2, 129.1, 128.7, 128.6, 128.3,
128.2, 128.0, 127.5, 126.6, 126.5, 125.6, 120.1, 119.9, 118.8, 114.7,
98.0, 51.8, 34.3, 34.1; MS (-c ESI) 619 (M - 1). Anal. Calcd for
C39H32N4O2S: C 75.46, H 5.20, N 9.03. Found: C 75.57, H 5.32, N
8.98.
(5S,4′R,2′Z,5′E) or (5R,4′S,2′Z,5′E)-methyl 1,4,4′,5′-tetrahydro-
1,3,4-triphenyl-5′-(2-phenylethylidene)-2′-(phenylimino)spiro[3H-
1,2,4-triazole-5,3′(2′H)-thiophene]-4′-carboxylate (15a-I): 806 mg,
65%, yellow solid (without recrystallization), mp 96-97 °C; IR V
Methyl 1,4-dihydro-5′-phenethyl-1,1′,3,4-tetraphenyl-2′-thioxo-
spiro[3H-1,2,4-triazole-5,3′(2′H)-pyrrole]-4′-carboxylate (18a): 273
mg, 22%, green crystals, mp 167-168 °C; IR V (cm-1) 1705, 1629,
1
(cm-1) 1744, 1626, 1593, 1492; H NMR (500 MHz, CDCl3) δ
(ppm) 7.59 (dd, J ) 7.3, 1.5 Hz, 2H), 7.37 (t, J ) 8.0 Hz, 2H),
7.26-7.32 (m, 9H), 7.23-7.24 (m, 5H), 7.14-7.18 (m, 4H), 7.07
(t, J ) 7.5 Hz, 1H), 6.97 (t, J ) 7.0 Hz, 1H), 6.08 (d, J ) 7.5 Hz,
2H), 5.88 (dt, J ) 6.1, 2.6 Hz, 1H), 4.91 (t, J ) 1.1 Hz, 1H), 3.67
(s, 3H), 3.48 (dd, J ) 16.1, 6.2 Hz, 1H), 3.30 (dd, J ) 16.2, 8.5
Hz, 1H); 13C NMR (75 MHz, CDCl3) δ (ppm) 169.8, 165.0, 151.5,
147.5, 140.8, 139.4, 139.0, 129.24, 129.20, 129.0, 128.7, 128.6,
128.44, 128.38, 127.8, 127.7, 127.4, 127.2, 126.60, 126.56, 125.0,
119.9, 118.5, 114.7, 98.1, 53.4, 52.9, 36.6; HRMS (TOF-EI)
620.2252, C39H32N4O2S required 620.2246.
1
1594, 1492; H NMR (500 MHz) δ (ppm) 7.57-7.61 (m, 3H),
7.54 (d, J ) 7.3 Hz, 2H), 7.23-7.34 (m, 8H), 7.15-7.21 (m, 4H),
7.12 (d, J ) 8.0 Hz, 2H), 7.06 (d, J ) 7.5 Hz, 2H), 6.88 (t, J ) 6.8
Hz, 2H), 6.84 (d, J ) 7.0 Hz, 2H), 3.74 (s, 3H), 2.91-2.97 (m,
1H), 2.82-2.87 (m, 1H), 2.53 (t, J ) 8.4 Hz, 2H); 13C NMR (125
MHz) δ (ppm) 207.4, 162.5, 160.4, 147.4, 143.2, 139.9, 138.1,
135.9, 130.2, 130.1, 129.9, 129.1, 128.8, 128.7, 128.6, 128.4, 128.2,
128.1, 127.8, 127.5, 126.9, 126.5, 120.1, 114.8, 111.2, 95.2, 51.4,
33.4, 29.2; MS (-c ESI) 619 (M - 1). Anal. Calcd for C39H32N4O2S:
C 75.46, H 5.20, N 9.03. Found: C 75.16, H 5.42, N 8.79.
Computational Methods. Density functional calculations have
been performed with the Gaussian 03 program package.11 The
geometric parameters of the possible transition states, reactants and
products are optimized with B3LYP/6-31G* method, and verified
with the number of imaginary frequencies. In order to confirm
whether the reactions proceed in a concerted or a stepwise way,
Intrinsic Reaction Coordiates (IRC)12 have been traced for the
relevant reaction paths.
(5R,4′R,2′Z,5′E)- or (5S,4′S,2′Z,5′E)-methyl 1,4,4′,5′-tetrahydro-
1,3,4-triphenyl-5′-(2-phenylethylidene)-2′-(phenylimino)spiro[3H-
1,2,4-triazole-5,3′(2′H)-thiophene]-4′-carboxylate (15a-II): 81 mg,
13%, yellow crystals, mp 153-154 °C; IR V (cm-1) 1750, 1633,
1592, 1487; 1H NMR (500 MHz, CDCl3) δ (ppm) 7.55 (d, J ) 7.2
Hz, 2H), 7.44 (d, J ) 7.8 Hz, 2H), 7.23-7.35 (m, 10H), 7.13-7.21
(m, 7H), 7.00-7.06 (m, 2H), 6.20 (d, J ) 7.7 Hz, 2H), 5.86 (t, J
) 6.8 Hz, 1H), 4.58 (s, 1H), 3.64 (s, 3H), 3.49 (dd, J ) 16.2, 6.6
Hz, 1H), 3.35 (dd, J ) 16.1, 8.4 Hz, 1H); 13C NMR (125 MHz,
CDCl3) δ (ppm) 168.7, 166.1, 151.6, 149.5, 143.7, 139.0, 138.5,
129.4, 129.2, 129.1, 128.7, 128.44, 128.39, 128.3, 128.22, 127.8,
127.1, 127.0, 126.5, 124.9, 122.0, 119.5, 118.5, 99.8, 57.0, 52.9,
36.2; MS (-c ESI): 619 (M - 1). Anal. Calcd for C39H32N4O2S: C
75.46, H 5.20, N 9.03. Found: C 75.62, H 5.38, N 8.74.
Acknowledgment. This work was supported by the National
Natural Science Foundation of China for Distinguished Young
Scholars (No. 20525207), National Natural Science Foundation
of China (No. 20832006 and 20672013), and Beijing Municipal
Commission of Education.
(5S,4′R,E)- or (5R,4′S,E)-methyl 1,4-dihydro-1,1′,3,4-tetraphe-
nyl-5′-(2-phenylethylidene)-2′-thioxospiro[3H-1,2,4-triazole-5,3′-
pyrrolidine]-4′-carboxylate (16a-I): 93 mg, 15%, yellow crystals,
Supporting Information Available: The experimental pro-
cedures for the reactions of 2-arylthiocarbamoyl benzimidazo-
lium salts 5, imidazolinium salts 1,0 and triazolium salts 14
with methoxycarbonylallenes 6, full characterization for products
7, 11, 12, 13, 15, 16, 17, and 18 excluding those byproducts
1
mp 177-178 °C; IR V (cm-1) 1746, 1594, 1492; H NMR (500
MHz) δ (ppm) 7.56 (d, J ) 7.3 Hz, 2H), 7.53 (br s, 1H), 7.41 (br
s, 2H), 7.37 (t, J ) 7.7 Hz, 2H), 7.20-7.32 (m, 14H), 7.17 (d, J )
7.7 Hz, 2H), 6.99 (t, J ) 7.2 Hz, 1H), 6.66 (br s, 1H), 5.19 (t, J )
7.0 Hz, 1H), 5.03 (s, 1H), 3.57 (s, 3H), 3.48 (dd, J ) 16.5, 7.0 Hz,
1H), 3.24 (dd, J ) 16.4, 8.1 Hz, 1H); 13C NMR (125 MHz) δ (ppm)
190.4, 169.2, 147.5, 141.3, 139.3, 139.1, 138.9, 137.3, 130.2, 129.4,
129.3, 129.2, 128.6, 128.4, 128.0, 127.7, 127.0, 126.5, 126.4, 120.6,
115.6, 112.2, 97.2, 52.8, 49.4, 34.3; MS (-c ESI): 619 (M - 1).
Anal. Calcd for C39H32N4O2S: C 75.46, H 5.20, N 9.03. Found: C
75.29, H 5.40, N 8.92.
1
without isolation, copies of H NMR and 13C NMR spectra of
products 7, 11, 12, 13, 15, 16, 17, and 18, as well as single
crystal data of 7a, 11a, 12g, 13a, 15e-I, 16e-I, 16e-II, and 17e
(CIF). This material is available free of charge via the Internet
at http://pubs.acs.org.
(5R,4′R,E)- or (5S,4′S,E)-methyl 1,4-dihydro-1,1′,3,4-tetraphe-
nyl-5′-(2-phenylethylidene)-2′-thioxospiro[3H-1,2,4-triazole-5,3′-
pyrrolidine]-4′-carboxylate (16a-II): 31 mg, 5%, yellow crystals,
JO802687M
(11) See the Supporting Information.
(12) (a) Gonzalez, C.; Schlegel, H. B. J. Chem. Phys. 1989, 90, 2154–2161.
(b) Gonzalez, C.; Schlegel, H. B. J. Phys. Chem. 1990, 94, 5523–5527.
1
mp 164-165 °C; IR V (cm-1) 1748, 1593, 1493; H NMR (500
MHz) δ (ppm) 7.49 (t, J ) 7.3 Hz, 4H), 7.43 (d, J ) 7.1 Hz, 1H),
J. Org. Chem. Vol. 74, No. 6, 2009 2367