Synthesis of novel synthetic intermediates from the reaction of benzimidazole and triazole carbenes with ketenimines and their application in the construction of spiro-pyrroles

Article abstract of DOI:10.1039/b915215f

2-(2-Alkoxycarbonyl-1-arylamino-1-propenyl)benzimidazolium and 5-(2-alkoxycarbonyl-1-arylamino-1-propenyl)triazolium salts were synthesized in good yields from the reaction of benzimidazole and triazole carbenes with ketenimines. Upon treatment with a bas

Full text of DOI:10.1039/b915215f

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www.rsc.org/obc | Organic & Biomolecular Chemistry
Synthesis of novel synthetic intermediates from the reaction of benzimidazole
and triazole carbenes with ketenimines and their application in the
construction of spiro-pyrroles†
Jun-Ming Mo, Yang-Guang Ma and Ying Cheng*
Received 27th July 2009, Accepted 14th September 2009
First published as an Advance Article on the web 14th October 2009
DOI: 10.1039/b915215f
2-(2-Alkoxycarbonyl-1-arylamino-1-propenyl)benzimidazolium and 5-(2-alkoxycarbonyl-1-
arylamino-1-propenyl)triazolium salts were synthesized in good yields from the reaction of
benzimidazole and triazole carbenes with ketenimines. Upon treatment with a base, both salts were
converted into novel 1,3-dipoles which underwent [3+2] cycloaddition reactions with electron-deficient
alkynes and allenes to produce benzimidazole-spiro-pyrroles or triazole-spiro-pyrroles. This work
provides novel synthons for the construction of multifunctional spiro-pyrrole derivatives that are not
easy accessible by other synthetic methods and are potentially amenable to further transformations.
synthons for the construction of novel spiro- and fused thiophene
Introduction
or pyrrole derivatives by our group.13 Although reactions be-
Nucleophilic carbenes, especially N-heterocyclic carbenes are
tween nucleophilic carbenes and different heterocumulenes have
versatile intermediates in organic synthesis.1 Among the reactions
been well documented, their reaction with ketenimines that are
of nucleophilic carbenes, those with various heterocumulenes have
structurally similar to isocyanates and ketenes have been rarely
been continuously explored and have gained important appli-
reported. Very recently, we found that thiazole and benzothia-
cations. For example, imidazoline carbenes, oxazoline carbenes,
zole carbenes underwent cycloaddition with two equivalents of
acyclic or cyclic dioxycarbene and dithiocarbenes undergo [4+1]-
ketenimines to produce thiazole- and benzothiazole-spiro-pyrrole
derivatives in good yields.14 The reaction was proposed to proceed
cycloadditions with vinyl isocyanates to afford hydroindolones
in good yields,2 while with aryl isocyanates, the nucleophilic
carbenes can either afford 1+1 adducts indole-2-ones3 or 1+2
adducts imidazoline-2,4-dione derivatives4 depending on the
structures of both reactants. Based on the addition–cyclization
reactions of nucleophilic carbenes with isocyanates, Rigby and
co-workers have successfully applied the reaction of dimethoxy-
carbene and bis(alkylthio)carbene with vinyl or indole isocyanates
to the total syntheses of alkaloids tazettine, mesembrine and
phenserine.5 Besides isocyanates, nucleophilic carbenes can also
undergo cyclization reactions with ketenes. For instance, imi-
dazoline carbenes, dioxycarbenes and dithiocarbenes participate
in efficient [4+1]-cycloadditions with vinyl ketenes or bis-ketene
producing cyclopentenone or cyclopentenedione derivatives.6 On
the other hand, the cyclization between dimethoxycarbene and
diphenylketene followed a different pathway to form a 1+2 adduct,
2,5-bis(diphenylmethylene)-4,4-dimethoxy-1,3-dioxolane.7 In ad-
dition to cycloaddition with heterocumulenes to afford cyclic prod-
ucts, N-heterocyclic carbenes are also known to form stable zwitte-
rions in the nucleophilic addition to cumulenes and heterocumu-
lenes, such as allenoates,8 isothiocyanates,9 isoselenocyanates,10
carbon dioxide11 and carbon disulfide.12 In recent years, the
ambident bis-dipoles derived from the addition of N-heterocyclic
carbenes to aryl isothiocyanates have been developed into versatile
=
via a tandem nucleophilic addition of carbene to the C N bond
of ketenimine followed by [3+2] cycloaddition of the 1,3-dipolar
=
intermediate with the C C bond of ketenimine. However, the 1,3-
dipolar intermediates could not be isolated. We considered that
the sulfur atom of thiazoles was not a strong enough electron
donor to stabilize the cation centers of dipolar intermediates in
these reactions. To find new types of C+–C–N- 1,3-dipole that
can be used as versatile synthons in the construction of novel
pyrrole derivatives, we undertook the current study of the reactions
of benzimidazole and triazole carbenes with ketenimines, and
explored their synthetic applications.
Results and discussion
We started this work with the investigation of the reaction
between benzimidazole carbenes and ketenimines. The benzim-
idazole carbenes were generated in situ from the treatment of
benzimidazolium salts 1 with a base. Initially, in dry THF and
at room temperature, 1,3-dibenzylbenzimidazolium salt 1c was
treated with NaH for 20 min and then reacted with methyl 3-(p-
methoxyphenyl)imino-2-methylacrylate 2c for 3 h. The reaction
gave product 3c in 40% yield. We then optimized the reaction con-
ditions by varying base, reaction temperature and solvent. It was
found that the best yield of product 3c (85%) was obtained using
t-BuOK as a base in THF at - 20 ◦C (Table 1, entry 5). Elevation of
the reaction temperature in THF led to a slight decrease of the yield
of product. Reactions that used NaH, DBU or Hu¨nig’s base, or
reactions performed in other solvents including dichloromethane,
College of Chemistry, Beijing Normal University, Beijing 100875, China.
E-mail: ycheng2@bnu.edu.cn; Fax: +861058805558; Tel: +861058805558
† Electronic supplementary information (ESI) available: Further experi-
mental and characterization details. CCDC reference numbers 740317–
740322. For ESI and crystallographic data in CIF or other electronic
format see DOI: 10.1039/b915215f
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Table 1 The reaction of 1,3-dibenzylbenzimidazolium salt 1c with 3-(p-methoxyphenyl)imino-2-methylacrylate 2c in the presence of a base under
different conditions
Reaction conditionsa
Entry
base
solvent
temp.
rt
time
Yield of 3cb
1
2
3
4
5
6
7
8
9
NaH
NaH
DBU
THF
THF
THF
THF
THF
THF
THF
CH2Cl2
CH3CN
Toluene
n-Hexane
3 h
5 h
40
78
16
-
85
79
72
76
54
8
-20 ◦
-20 ◦
-20 ◦
-20 ◦
rt
C
C
C
C
12 h
10 h
1 h
0.5 h
0.5 h
1 h
1 h
11 h
14 h
(i-Pr)2NEt
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
reflux
-20 ◦
-20 ◦
-20 ◦
-20 ◦
C
C
C
C
10
11
-
a 1c:2c:base = 1:1:1; b Isolated yields.
acetonitrile, toluene and hexane, afforded product in a lower or
very poor yield (Table 1).
To examine the generality of this reaction, both benzimidazole
and triazole carbenes bearing alkyl, benzyl or phenyl groups were
employed to react with ketenimines substituted by different aryl
groups at the nitrogen atom under optimized conditions. As shown
in Scheme 1 and Table 2, the reactions of benzimidazolium 1 and
triazolium salts 4 with ketenimines 2 in the presence of t-BuOK
proceeded rapidly and efficiently at -20 ◦C to afford products
3 and 5, respectively, in 58–92% yields. Since some chloride or
bromide salts of 3 and 5 are not easily purified, these products
were then converted into tetrafluoroborate salts by treatment with
NH4BF4.
The structures of products 3 and 5 were elucidated on the
basis of spectroscopic data and microanalysis. The NMR spectra,
mass data and elemental analyses indicated that the constitutions
of products 3 or 5 were 1+1 adducts of benzimidazolium salts
1 or triazolium salts 4 with ketenimines 2. According to the
spectroscopic data, products 3 and 5 were assigned as 1,3-dialkyl-
2-(2-alkoxycarbonyl-1-arylamino-1-propenyl)benzimidazolium
Scheme 1 The reaction of benzimidazolium 1 or triazolium salts 4 with
ketenimines 2 in the presence of t-BuOK.
phenyl-1,2,4-triazolium salts, respectively. X-Ray diffraction
and
5-(2-alkoxycarbonyl-1-arylamino-1-propenyl)-1,3,4-tri-
analysis of 3g ascertained the structural assignment, which
Table 2 The reactions of benzimidazolium 1 and triazolium salts 4 with ketenimines 2 in the presence of t-BuOK under optimized conditionsa
Entry
1 or 4
R, X
2
Ar, R1
3 or 5
X
Yield (%)b
1
2
3
4
5
6
7
8
9
1a
1b
1c
1d
1e
1e
1f
4a
4a
4a
4a
Et, Br
n-Bu, Br
Bn, Cl
p-MeBn, Cl
p-ClBn, Cl
p-ClBn, Cl
p-BrBn, Br
Ph, Cl
Ph, Cl
Ph, Cl
2a
2a
2c
2a
2a
2b
2a
2a
2b
2c
2d
Ph, Me
Ph, Me
p-MeOC6H4, Me
Ph, Me
Ph, Me
p-ClC6H4, Et
Ph, Me
3a
3b
3c
3d
3e
3f
3g
5a
5b
5c
5d
Br
BF4
Cl
Cl
Cl
Cl
BF4
Cl
BF4
Cl
BF4
85
80
85
92
74
72
68
81
68
70
74
Ph, Me
p-ClC6H4, Et
p-MeOC6H4, Me
p-MeC6H4, Me
10
11
Ph, Cl
a Reaction conditions: 1 or 4:2 = 1:1, t-BuOK, THF, -20 ◦C, 1 h. b Isolated yields.
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Fig. 1 Ortep drawing of X-ray structures of 4g, 11d, 17d, 18e, 19b-I, 20b (50% probability was chosen for the ellipsoids).
showed the E-configured carbon–carbon double bond of 3g
(Fig. 1).15 Theoretically, products 3 and 5 can have Z-configured
and E-configured stereoisomers, however, no Z-configured isomer
was observed in these reactions.
former did not further react with ketenimines under reaction
conditions while the latter did. This difference is easily understood
because the cation centers of intermediates 8 or 9 that are stabilized
by the two nitrogen atoms of benzimidazole or triazole are more
stable than the cation centers substituted by one nitrogen and one
sulfur atom of thiazole or benzothiazole.
Since we have proved that thiazole and benzothiazole carbenes
undergo a tandem nucleophilic addition/[3+2] cycloaddition
reaction with ketenimines 2 in our previous study,14 the formation
of (2-alkoxycarbonyl-1-arylamino-1-propenyl)benzimidazolium 3
or -triazolium salts 5 can be best explained by the nucleophilic
addition of benzimidazole carbenes 6 or triazole carbenes 7 to
ketenimines 2 to form 1,3-dipolar intermediates 8 or 9, followed
by protonation of dipoles 8 or 9 with butanol or water in solvent
and/or in the eluent of column chromatography (Scheme 2).
Comparing the current reactions with those between thiazole
or benzothiazole carbenes and ketenimines 2, we found that the
dipolar intermediates 8 or 9 derived from benzimidazole or triazole
carbenes and ketenimines 2 are more stable than the 1+1 adducts
of thiazole or benzothiazole carbenes with ketenimine, since the
With the 2-(2-alkoxycarbonyl-1-arylamino-1-propenyl)benzi-
midazolium
3
and 5-(2-alkoxycarbonyl-1-arylamino-1-pro-
penyl)triazolium salts 5 in hand, we further explored their
applications in organic synthesis. We considered that both
benzimidazolium 3 and 1,2,4-triazolium salts 5 can be converted
into zwitterions by deprotonation of the arylamino groups of 3
and 5, and therefore they probably could be used as the precursors
of novel 1,3-dipoles. Thus, 1,3-dibenzyl-2-(2-methoxycarbonyl-1-
(p-methoxyphenyl)amino-1-propenyl)benzimidazolium chloride
3c was treated with t-BuOK and then reacted with ethyl propiolate
in THF at room temperature. A red product 11c was isolated in
41% yield from this reaction. The reaction conditions were then
optimized by varying solvents and temperature. As indicated
in Table 3, the best yield of 11c (59%) was obtained from the
reaction in toluene at 80 ◦C. Other solvents including THF,
dichloromethane, acetonitrile and hexane led to lower yields
and the reaction temperature only slightly affected the yield of
product.
The generality was examined by reacting benzimidazolium 3
and triazolium salts 5 with ethyl propiolate under optimized con-
ditions. Benzimidazolium 3 or triazolium salts 5 were mixed with
t-BuOK in toluene at room temperature, and then reacted
with ethyl propiolate 10 at 80 ◦C for half an hour to af-
ford benzimidazole-spiro-dihydropyrroles 11 or triazole-spiro-
dihydropyrroles 12 in moderate yields (Scheme 3, and Table 4
entries 1–8). The scope of the reaction was further studied by
replacement of ethyl propiolate with dimethyl acetylenedicarboxy-
late (DMAD). Under conditions identical to those used for ethyl
propiolate, benzimidazolium 3 and 1,2,4-triazolium salts 5 were
deprotonated with t-BuOK and reacted with DMAD rapidly to
Scheme 2 The proposed mechanism for the reaction of benzimidazolium
1 or triazolium salts 4 with ketenimines 2 in the presence of t-BuOK.
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Table 3 The reaction of 1,3-dibenzyl-2-[2-methoxycarbonyl-1-(p-
methoxyphenyl)amino-1-propenyl]benzimidazolium chloride 3c with
ethyl propiolate in the presence of t-BuOK under different conditions
Reaction conditionsa
Entry
solvent
temp.
time
Yield of 11cb
1
2
3
4
5
6
7
Toluene
Toluene
Toluene
THF
CH2Cl2
CH3CN
n-Hexane
rt
3 h
51
59
56
41
29
29
18
80
reflux
rt
rt
rt
0.5 h
0.5 h
3 h
3 h
5 h
Scheme 3 The reaction of 2-(2-alkoxycarbonyl-1-arylamino-1-propenyl)-
benzimidazolium 3 and 5-(2-alkoxycarbonyl-1-arylamino-1-propenyl)tri-
azolium salts 5 with ethyl propiolate and dimethyl acetylenedicarboxylate.
rt
5 h
a 3c:10:base = 1:1:1; b Isolated yields.
When the reaction temperature was elevated, the yield of product
18b increased. To our delight, we observed the transformation of
product 17b to 18b in refluxing toluene. Finally, 53% yield of 18b
was isolated from the reaction in refluxing toluene for 48 h. Thus,
the two isomers 17b and 18b can be obtained respectively as major
product under different conditions.
The reactions of different benzimidazolium salts 3 with allenes
16 were then carried out under the optimized conditions for
selective formation of products 17 or 18. In toluene and at
60 ◦C, benzimidazolium salts 3 were treated with t-BuOK and
reacted with allenes 16 for 3 h to produce benzimidazole-spiro-
tetrahydropyrroles 17 in 48–62%, while the same reaction afforded
46–53% yields of benzimidazole-spiro-dihydropyrroles 18 along
with 14–15% yields of 17 after heating in refluxing toluene for 48 h
(Scheme 4, equ. 1; Table 6, entries 1–7).
afford spiro-dihydropyrroles 14 and 15, respectively, in 58–71%
yields (Scheme 3, and Table 4 entries 9–17).
We next turned our attention to the reactions of benzimi-
dazolium salts 3 and triazolium salts 5 with electron-deficient
allenes. Under the optimized conditions for the aforementioned
reactions (toluene, 80 ◦C), the reaction of 3e with methyl 5-
phenylpenta-2,3-dienoate 16b in the presence of t-BuOK formed
two products 17b and 18b in 50% and 8% yields respectively
in 3 h. Spectroscopic data confirmed that compounds 17b and
18b were two constitutional isomers. The major product 17b was
derived from cycloaddition of 1,3-dipolar intermediate 8 with
=
the benzyl-substituted C C bond (electron-rich double bond),
while the minor one 18b was the adduct of the 1,3-dipole and the
ester-substituted double bond (electron-deficient double bond).
To improve the selectivity for the formation of 17b and 18b, the
reaction of 3e with 16b was examined at different temperatures
Followed the reaction of benzimidazolium salts 3 with allenes,
triazolium salts 5 were also employed to react with allenes
16. In toluene and at 60 ◦C, triazolium salts 5 reacted with
allenes 16 in the presence of t-BuOK to afford two triazole-
spiro-tetrahydropyrroles 19-I and 19-II in 26–49% and 14–24%
◦
(Table 5). It was found that, at room temperature and at 60 C,
only product 17b was isolated in 40% and 62% yields respectively.
Table 4 The reaction of 3 or 5 with ethyl propiolate 10 and with dimethyl acetylenedicarboxylate (DMAD) 13 in the presence of t-BuOK under optimized
conditionsa
Entry
Starting materials
R
R1
Ar
Product
Yield (%)b
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
3c + 10
3d + 10
3e + 10
3f + 10
3g + 10
5b + 10
5c + 10
5d + 10
3b +13
3d +13
3e +13
3g + 13
5a + 13
5b +13
5c + 13
5d + 13
Bn
Me
Me
Me
Et
Me
Et
Me
Me
Me
Me
Me
Me
Me
Et
p-MeOC6H4
Ph
Ph
p-ClC6H4
Ph
p-ClC6H4
p-MeOC6H4
p-MeC6H4
Ph
Ph
Ph
11c
11d
11e
11f
59
61
58
47
54
55
68
57
70
69
58
58
71
58
61
64
p-MeBn
p-ClBn
p-ClBn
p-BrBn
Ph
Ph
Ph
n-Bu
p-MeBn
p-ClBn
p-BrBn
Ph
Ph
Ph
11g
12b
12c
12d
14b
14d
14e
14g
15a
15b
15c
15d
Ph
Ph
p-ClC6H4
p-MeOC6H4
p-MeC6H4
Me
Me
Ph
a Toluene, 80 ◦C, 0.5 h; b Isolated yields.
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Table 5 The reaction of 1,3-di(p-chlorobenzyl)-2-(2-methoxycarbonyl-
1-phenylamino-1-propenyl)benzimidazolium chloride 3e with methyl 5-
phenylpenta-2,3-dienoate 16b in the presence of t-BuOK in toluene
yields, respectively (Scheme 4, equ. 2; Table 6, entries 8–10.).
Products 19-I and 19-II were confirmed to be diastereoisomers
by their spectroscopic data, and both of them were obtained
from the cycloaddition of dipolar intermediates 9 with the
ester-substituted double bond of allenes 16. Isomers 19-I and
19-II could not transform into each other by varying the reaction
conditions. However, triazole-spiro-tetrahydropyrroles 19-I were
observed to convert slowly into triazole-spiro-dihydropyrroles
20 during the recrystallization process. The quantitative
transformation of triazole-spiro-tetrahydropyrroles 19 to triazole-
spiro-dihydropyrroles 20 was achieved by keeping 19 in deuterium
chloroform for a few days (Scheme 4, equ. 2; Table 6, entries
11–12).
The structures of the products were elucidated on the basis
of spectroscopic data and microanalysis. The NMR spectra,
mass data and elemental analyses indicated products 11, 12,
14, 15, 17, 18, 19, or 20 being derived from 1+1 addition of
(2-alkoxycarbonyl-1-arylamino-1-propenyl)benzimidazolium 3 or
-triazolium salts 5 with alkynes 10, 13 or allenes 16, with the loss
of a molecule of HCl, HBr or HBF4. The exact structures of 11d,
Reaction conditionsa
Yield (%)b
Entry
solvent
temp.
time
17b
18b
1
2
3
4
5
6
7
8
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
rt
5 h
3 h
3 h
3 h
12 h
24 h
36 h
48 h
40
62
50
48
36
33
20
14
-
-
60 ◦
C
C
80 ◦
8
reflux
reflux
reflux
reflux
reflux
16
29
35
47
53
a 3c:16b:base = 1:1:1; b Isolated yields.
Table 6 The reaction of 3 or 5 with allenes 16 in the presence of t-BuOK
Starting materials
Entry
R
R1
Ar
R2
Reaction conditions
Yield of product (%)a
1
2
3
3e
3e
3e
p-ClBn
p-ClBn
p-ClBn
Me
Me
Me
Ph
Ph
Ph
16a
16b
16b
Et
Bn
Bn
Toluene, 60 ◦C, 5 h
Toluene, 60 ◦C, 3 h
Toluene, reflux, 48 h
17a
58
62
14
53
53
48
51
15
46
49
14
26
24
38
21
17b
17b
18b
4
5
6
7
3f
p-ClBn
p-BrBn
p-BrBn
p-BrBn
Et
p-ClC6H4
16b
16a
16b
16b
Bn
Et
Bn
Bn
Toluene, 60 ◦C, 5 h
Toluene, 60 ◦C, 5 h
Toluene, 60 ◦C, 3 h
Toluene, reflux, 48 h
17c
3g
3g
3g
Me
Me
Me
Ph
Ph
Ph
17d
17e
17e
18e
8
9
5a
5c
5d
Ph
Ph
Ph
Ph
Ph
Me
Me
Me
Me
Me
Ph
16a
16a
16a
Et
Et
Et
Et
Et
Toluene, 60 ◦C, 3 h
Toluene, 60 ◦C, 3 h
Toluene, 60 ◦C, 3 h
CDCl3, rt, 1–3 days
CDCl3, rt, 1–3 days
19a-I
19a-II
19b-I
19b-II
19c-I
19c-II
20a
p-MeOC6H4
p-MeC6H4
Ph
10
11
12
19a-I
19a-II
19b-I
19b-II
quantitative conversionb
p-MeOC6H4
20b
quantitative conversionb
a Isolated yields. b Detected by TLC and 1H NMR.
Scheme 4 The reaction of 2-(2-alkoxycarbonyl-1-arylamino-1-propenyl)benzimidazolium 3 or 5-(2-alkoxycarbonyl-1-arylamino-1-propenyl)triazolium
salts 5 with allenes 16 in the presence of t-BuOK.
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=
17d, 18e, 19b-I and 20b were unambiguously established by single
crystal X-ray diffraction analysis (Fig. 1).15 It is worth noting that
in the reactions of benzimidazolium 3 and triazolium salts 5 with
allenes 16, only E,E-configured products 17 and 19 were detected.
substituted C C bond) and an electron-rich C(2)–C(3) double
=
bond (alkyl substituted C C bond), the cycloaddition of dipolar
intermediates 8 and 9 with allenes 16 was regioselective. In the re-
action of benzimidazole carbene-derived dipoles 8 with allenes 16,
dipoles 8 selectively attacked the electron-rich C(2)–C(3) double
bond of allenes to form benzimidazole-spiro-tetrahydropyrroles
17 at a lower temperature. At a higher temperature, spiro-
tetrahydropyrroles 17 isomerized into their constitutional isomers
23, probably via zwitterionic intermediates that can be represented
as two resonant structures 21 and 22. Under the reaction condi-
tions, intermediates 23 rearranged into thermodynamically more
=
The predominant formation of E-configured exocyclic C C bonds
of products 17 and 19 was most probably due to the fact that the
E-configured double bonds could avoid the huge steric repulsion
between the N-aryl group on the pyrrole ring and the carbonyl or
=
alkyl groups on the exocyclic C C bonds.
The formation of benzimidazole-spiro-pyrroles 11, 14, 17,
18 or triazole-spiro-pyrroles 12, 15, 19, 20 can be best
explained by [3+2] cycloaddition of the dipolar intermedi-
ates 8 or 9 with alkynes or allenes. Deprotonation of 2-(2-
alkoxycarbonyl-1-arylamino-1-propenyl)benzimidazolium 3 or 5-
(2-alkoxycarbonyl-1-arylamino-1-propenyl)triazolium salts5 with
t-BuOK formed 1,3-dipolar intermediates 8 or 9, respectively.
Cycloaddition of dipoles 8 or 9 with ethyl propiolate or DMAD
produced benzimidazole-spiro-dihydropyrroles 11, 14 or triazole-
spiro-dihydropyrroles 12, 15, respectively (Scheme 5).
=
stable conjugated products 18 by shifting the exocyclic C C bond
of 23 to the endocyclic double bond. Since a concerted suprafacial
1,3-H shift is a symmetry forbidden process, the isomerization
of intermediates 23 to product 18 was most probably through
an allyl anion intermediate 24, by deprotonation of the acidic
proton adjacent both to carbonyl and vinyl groups in the presence
of t-BuOK. Contrary to benzimidazole carbene-derived dipoles
8, triazole carbene-derived dipoles 9 selectively cyclized with the
electron-deficient C(1)–C(2) double bond of allenes 16 to form a
pair of diastereomers 19-I and 19-II. In solvent, the spontaneous
isomerization of triazole-spiro-tetrahydropyrroles 19 to triazole-
spiro-dihydropyrroles 20 should followed the same pathway as that
from intermediates 23 to products 18, since triazole derivatives 19
are organic bases that probably self-catalyze the rearrangement of
double bond (Scheme 6).
The different selectivity of benzimidazole and triazole carbene-
derived dipoles 8 and 9 toward two double bonds of allenes 16 was
in good agreement with our recent discovery on the regioselectivity
of [3+2] cycloaddition reaction of allenes 16 with 2-thiocarbamoyl
benzimidazolium 26 and with 2-thiocarbamoyl triazolium inner
salts 28, which were ambident 1,3-dipoles derived respectively
from 1+1 addition of benzimidazole and triazole carbenes with
aryl isothiocyanates. We have demonstrated experimentally that
2-thiocarbamoyl benzimidazolium inner salts 26 predominately
undergo cycloaddition reaction with the electron-rich C(2)–C(3)
double bond of allenes 16, while 2-thiocarbamoyl triazolium
inner salts 28 prefer to cyclize with the electron-deficient
Scheme 5 The proposed mechanism for the formation of products 11,
12, 14, 15.
Since allenes 16 have two different carbon–carbon double
bonds, an electron-deficient C(1)–C(2) double bond (carbonyl
Scheme 6 The proposed mechanisms for the formation of products 17, 18, 19, 20.
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yields. This work has provided novel and versatile synthons
for the construction of multifunctional spiro-pyrrole derivatives,
which are not easy accessible by other synthetic methods and are
potentially amenable to further transformations.
Experimental
Melting points are uncorrected. 1H NMR (500 or 400 MHz) and
13C NMR (125 or 100 MHz) were recorded in the indicated sol-
vents. J values are reported in Hz. IR spectra were recorded using
an AVATAR 360 FT-IR spectrometer. Mass spectra were recorded
on a Trace MS (EI) or Surveyor MSQ Plus (ESI) instrument
and elemental analyses were performed on a GMBH Vario EL
instrument. Column chromatography was performed using 200–
300 mesh silica gel or neutral Al2O3. For full characterization for
all isolated products see the ESI.†
Scheme 7 The reaction of 2-thiocarbamoyl benzimidazolium 26 and
2-thiocarbamoyl triazolium inner salts 28 with allenes 16.16
1. The preparation of 2-(2-alkoxycarbonyl-1-arylamino-
1-propenyl)benzimidazolium salts 3 or 5-(2-alkoxycarbonyl-1-
arylamino-1-propenyl)triazolium salts 5 from the reaction of
benzimidazole or triazole carbenes with ketenimines
C(1)–C(2) double bond of allenes 16 (Scheme 7).16 Generally, the
ester carbonyl-substituted C(1)–C(2) double bond is more active
than the alkyl-substituted C(2)–C(3) double bond toward nucle-
ophiles due to the electronic preference. However, our theoretical
study16 indicated that both the cycloaddition of benzimidazolium
Under a nitrogen atmosphere and at -20 ◦C, benzimidazolium
chloride or bromide salts 1 (0.5 mmol) or triazolium chloride
salts 4 (0.5 mmol) were mixed with t-BuOK (0.5 mmol) in dry
THF (30 mL) and stirred for 5 min. Ketenimines 2 (0.5 mmol)
were added to the reaction mixture and the mixture was stirred
at -20 ◦C for 1 h. After removal of solvent under vacuum at
room temperature, the residue was chromatographed on a neutral
Al2O3 column eluting with a mixture of acetone and methanol
(5:1). The eluent was evaporated and the 2-(2-alkoxycarbonyl-1-
arylamino-1-propenyl)benzimidazolium chlorides or bromides 3
or 5-(2-alkoxycarbonyl-1-arylamino-1-propenyl)triazolium chlo-
rides 5 were isolated in 68–93% or 68–81% yields, respectively. The
benzimidazolium or triazolium chlorides or bromides 3 or 5 were
converted into tetrafluoroborate salts by treatment with NH4BF4
in methanol.
=
inner salts 26 with the C(2) C(3) bond of allene 16 and triazolium
=
inner salts 28 with the C(1) C(2) bond of 16 are kinetically more
favorable than the other pathways. The unusual regioselectivity
of the reaction between benzimidazole dipole 26 and allene 16 is
most probably due to the repulsion between the phenyl ring of
benzimidazolium 26 and the ester carbonyl group of 16 in the
=
transition state of reaction between 26 and C(1) C(2) bond of 16.
That means the steric effect counterbalances the electronic effect in
this reaction. Comparing the current study illustrated in Scheme 6
with the previous work in Scheme 7, we found that although the
unstable dipolar intermediates 8 and the stable dipoles 26, or 9
and 28, are structurally different, the regioselectivity of their [3+2]
cycloaddition reaction with allenes 16 keeps quite the same. That
is the benzimidazole-carbene derived 1,3-dipoles prefer to react
(E)-1,3-Diethyl-2-(2-methoxycarbonyl-1-phenylamino-1-pro-
penyl)benzimidazolium bromide (3a). 85%, yellow crystals (ethyl
acetate and petroleum ether), mp 179–181 ◦C; vmax/cm-1 3342,
2729, 1688, 1590, 1546, 1514; dH (500 MHz, CDCl3) 10.34 (brs,
1H), 7.69–7.73 (m, 2H), 7.61 (dd, J = 6.0, 2.8 Hz, 2H), 7.31 (t, J =
8.1 Hz, 2H), 7.13 (d, J = 7.9 Hz, 2H), 7.03 (t, J = 7.4 Hz, 1H),
4.40–4.51 (m, 4H), 3.63 (s, 3H), 1.96 (s, 3H), 1.54 (t, J = 7.3 Hz,
6H); dC (125 MHz, CDCl3) 168.1, 147.3, 139.9, 131.4, 131.1, 129.0,
126.9, 123.0, 119.3, 113.3, 113.0, 52.1, 42.3, 16.4, 13.9; MS (ESI):
364 (M+). Anal. Calcd for C22H26BrN3O2: C 59.46, H 5.90, N 9.46;
Found: C 59.55, H 6.04, N 9.60.
=
with the C(2) C(3) bond of 16, but triazole-carbene derived 1,3-
=
dipoles prefer to react with the C(1) C(2) bond of 16. This work
further demonstrated that it is the structure of the heterocyclic
carbene that controls the regioselectivity of cycloaddition between
carbene-derived dipoles and allenes.
Conclusions
In summary, we have prepared 2-(2-alkoxycarbonyl-1-arylamino-
1-propenyl)benzimidazolium salts 3 and 5-(2-alkoxycarbonyl-1-
arylamino-1-propenyl)triazolium salts 5 in good to excellent
yields from the reaction of benzimidazole and triazole car-
benes with 3-arylimino-2-methylacrylates (C-alkoxycarbonyl-N-
arylketenimines). Benzimidazolium salts 3 and triazolium salts 5
were converted into novel 1,3-dipolar intermediates, namely 2-(2-
alkoxycarbonyl-1-arylamino-1-propenyl)benzimidazolium inner
salts and 5-(2-alkoxycarbonyl-1-arylamino-1-propenyl)triazolium
inner salts, by treatment with t-BuOK. These resulting dipo-
lar intermediates underwent [3+2] cycloaddition reactions with
electron-deficient alkynes and allenes to produce benzimidazole-
spiro-pyrroles or triazole-spiro-pyrroles generally in moderate
(E)-5-(2-Methoxycarbonyl-1-phenylamino-1-propenyl)-1,3,4-
triphenyl-1,2,4-triazolium chloride (5a). 81%, yellow crystals
(ethyl acetate and petroleum ether), mp 171–173 ◦C; vmax/cm-1
2698, 1676, 1589, 1541, 1496, 1451; dH (400 MHz, CDCl3) 11.96
(s, 1H), 7.98 (dd, J = 8.0, 2.0 Hz, 2H), 7.70–8.10 (br, 1H), 7.60 (d,
J = 7.4 Hz, 2H), 7.30–7.51 (m, 10H), 7.02 (t, J = 7.7 Hz, 2H), 6.82
(t, J = 7.3 Hz, 1H), 6.44 (d, J = 7.8 Hz, 2H), 3.63 (s, 3H), 1.33
(s, 3H); dC (100 MHz, CDCl3) 168.7, 153.5, 150.8, 139.7, 135.1,
131.9, 131.8, 131.24, 131.18, 130.6, 129.8, 129.52, 129.45, 128.8,
128.2, 127.8, 125.8, 123.0, 122.5, 119.2, 112.5, 52.1, 15.6; MS (EI):
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194 (100), 296 (60), 486 (M+-1, 6%), 487 (M+, 3%). Anal. Calcd
for C31H27ClN4O2: C 71.19, H 5.20, N 10.71; Found: C 70.92, H
5.09, N 10.42.
(EI): 44 (100), 313 (40), 502 (45), 561 (M+, 10%). Anal. Calcd for
C32H39N3O6: C 68.43, H 7.00, N 7.48; Found: C 68.66, H 6.93, N
7.47.
(E)-Dimethyl 2¢-(1-methoxycarbonylethylidene)-1,1¢3,4-tetra-
phenyl-1,1¢,2¢,4-tetrahydrospiro[1,2,4-triazole-2,3¢-pyrrole]-4¢,5¢-
dicarboxylate (15a). 71%, red crystals (ethyl acetate and
petroleum ether), mp 159–160 ◦C; vmax/cm-1 1748, 1713, 1620,
1593, 1493; dH (400 MHz, CDCl3) 7.48 (dd, J = 6.4, 1.7 Hz, 2H),
7.34 (dd, J = 6.4, 1.8 Hz, 2H), 7.21–7.29 (m, 11H), 7.13 (d, J =
7.7 Hz, 2H), 6.85 (t, J = 7.2 Hz, 1H), 6.61–6.63 (m, 2H), 3.70 (s,
3H), 3.64 (s, 3H), 3.55 (s, 3H), 1.35 (s, 3H); dC (100 MHz, CDCl3)
169.0, 162.8, 161.7, 150.5, 146.2, 143.9, 143.0, 138.7, 138.3, 129.3,
129.0, 128.9, 128.5, 128.3, 128.12, 128.07, 127.9, 126.9, 126.1,
119.4, 117.6, 114.1, 106.2, 93.7, 53.1, 52.7, 51.3, 16.5; MS (EI):
180 (100), 628 (M+, 15%). Anal. Calcd for C37H32N4O6: C 70.69,
H 5.13, N 8.91; Found: C 70.56, H 4.85, N 8.76.
2. General procedure for the reaction of 2-(2-alkoxycarbonyl-
1-arylamino-1-propenyl)benzimidazolium salts 3 or
5-(2-alkoxycarbonyl-1-arylamino-1-propenyl)triazolium salts 5
with ethyl propiolate or DMAD
Under a nitrogen atmosphere and at room temperature, benz-
imidazolium salts 3 (0.5 mmol) or triazolium salts 5 (0.5 mmol)
were mixed with t-BuOK (0.6 mmol) in dry toluene. After the
temperature was elevated to 80 ◦C, ethyl propiolate or DMAD
(0.6 mmol) was added to the mixture. The reaction mixture was
stirred at 80 ◦C for half an hour and then the solvent was removed
under vacuum. The products 11, 12, 14 or 15 were isolated by
chromatography on a silica gel column eluting with a mixture of
petroleum ether (60–90 ◦C) and ethyl acetate (5:1).
3. General procedure for the reaction of 2-(2-alkoxycarbonyl-
1-arylamino-1-propenyl)benzimidazolium salts 3 or
5-(2-alkoxycarbonyl-1-arylamino-1-propenyl)triazolium salts 5
with allenes 16
(E)-Ethyl
1,3-dibenzyl-2¢-(1-methoxycarbonylethylidene)-1¢-
(p-methoxyphenyl)-1,1¢,2¢,3-tetrahydrospiro[benzimidazole-2,3¢-
pyrrole]-4¢-carboxylate (11c). 53%, orange crystals (ethyl acetate
and petroleum ether), mp 172–173 ◦C; vmax/cm-1 1713, 1687,
1612, 1598, 1506; dH (400 MHz, CDCl3) 7.38 (d, J = 6.7 Hz, 4H),
7.27–7.29 (m, 6H), 7.09 (s, 1H), 6.82 (d, J = 8.8 Hz, 2H), 6.79 (d,
J = 8.8 Hz, 2H), 6.49 (dd, J = 5.2, 3.2 Hz, 2H), 6.15 (dd, J =
5.4, 3.2 Hz, 2H), 4.36 (d, J = 16.0 Hz, 2H), 4.30 (d, J = 16.0 Hz,
2H), 3.89 (q, J = 7.1 Hz, 2H), 3.79 (s, 3H), 3.09 (s, 3H), 1.59 (s,
3H), 0.88 (t, J = 7.1 Hz, 3H); dC (100 MHz, CDCl3) 170.2, 163.6,
157.8, 148.3, 147.7, 140.4, 138.6, 134.2, 128.3, 128.1, 126.9, 124.9,
117.7, 114.5, 114.0, 108.2, 103.3, 96.0, 59.3, 55.5, 52.0, 49.2, 17.7,
13.7; MS (EI): 90 (100), 395 (60), 615 (M+, 20%). Anal. Calcd for
C38H37N3O5: C 74.13, H 6.06, N 6.82; Found: C 73.80, H 6.22, N
6.73.
Method A. Under a nitrogen atmosphere, benzimidazolium
salts 3 (0.5 mmol) or triazolium salts 5 (0.5 mmol) were mixed with
t-BuOK (0.6 mmol) in dry toluene at room temperature. When the
temperature was elevated to 60 ◦C, allene 16 (0.5 mmol) was added
to the reaction mixture, and the mixture was stirred for 3–5 h at
◦
60 C. After removal of solvent under vacuum, the products 17,
or 19-I and 19-II were isolated, respectively, by chromatography
on a silica gel column eluting with a mixture of petroleum ether
(60–90 ◦C) and ethyl acetate (7:1). 19-I and 19-II can be converted
into 20 by standing in deuterium chloroform for a few days.
Method B. Under a nitrogen atmosphere and at room tem-
perature, benzimidazolium salts 3 (0.5 mmol) were mixed with
t-BuOK (0.6 mmol) in dry toluene. After allene 16 (0.5 mmol)
was added, the reaction mixture was stirred for 48 h in refluxing
toluene. The solvent was removed under vacuum, and the com-
pounds 18 and 17 were isolated as major and minor products by
chromatography on a silica gel column eluting with a mixture of
petroleum ether (60–90 ◦C) and ethyl acetate (7:1).
(E)-Ethyl 1¢-(p-chlorophenyl)-2¢-(1-ethoxycarbonylethylidene)-
1,3,4-triphenyl-1,1¢,2¢,4-tetrahydrospiro[1,2,4-triazole-2,3¢-pyr-
role]-4¢-carboxylate (12b). 56%, red crystals (ethyl acetate and
petroleum ether), mp 134–136 ◦C; vmax/cm-1 1716, 1613, 1593,
1493; dH (400 MHz, CDCl3) 7.47 (dd, J = 7.7, 1.3 Hz, 2H), 7.44
(s, 1H), 7.15–7.29 (m, 12H), 7.07 (d, J = 8.0 Hz, 2H), 6.80 (t,
J = 7.1 Hz, 1H), 6.60 (d, J = 8.7 Hz, 2H), 4.11–4.15 (m, 1H),
3.95–4.06 (m, 3H), 1.52 (s, 3H), 1.05 (t, J = 7.1 Hz, 3H), 1.01 (t,
J = 7.1 Hz, 3H); dC (100 MHz, CDCl3) 168.4, 163.1, 148.2, 146.1,
143.8, 143.3, 139.4, 138.8, 131.3, 129.4, 128.8, 128.7, 128.6, 128.5,
128.3, 128.1, 128.0, 126.7, 123.8, 119.1, 118.1, 114.3, 111.1, 94.2,
61.5, 59.7, 17.7, 14.2, 13.9; MS (EI): 180 (100), 632 (M+, 15%).
Anal. Calcd for C37H33ClN4O4: C 70.19, H 5.25, N 8.85; Found:
C 70.39, H 5.59, N 8.41.
(E,E)-Methyl
2-(1,3-di(p-chlorobenzyl)-4¢-ethyl-5¢-methoxy-
carbonylmethylidene - 1¢ - phenyl - 1,3 - dihydrospiro[benzimidazole -
2,3¢-pyrrolidine]-2¢-ylidene)propanoate (17a). 58% from method
A, yellow crystals (ethyl acetate and petroleum ether), mp 197–
199 ◦C; vmax/cm-1 1701, 1640, 1601, 1503, 1490; dH (400 MHz,
CDCl3) 7.43 (t, J = 8.0 Hz, 2H), 7.24–7.36 (m, 9H), 7.06 (d, J =
7.6 Hz, 2H), 6.58 (dt, J = 7.6, 1.0 Hz, 1H), 6.49 (dt, J = 7.6,
1.0 Hz, 1H), 6.09 (d, J = 7.3 Hz, 1H), 5.88 (d, J = 7.3 Hz, 1H),
4.76 (s, 1H), 4.63 (d, J = 17.9 Hz, 1H), 4.56 (d, J = 17.2 Hz, 1H),
4.51 (d, J = 17.2 Hz, 1H), 4.26 (d, J = 17.9 Hz, 1H), 4.21–4.23
(m, 1H), 3.49 (s, 3H), 2.86 (s, 3H), 1.97–2.05 (m, 1H), 1.52–1.58
(m, 1H), 1.41 (s, 3H), 0.83 (t, J = 7.4 Hz, 3H); dC (100 MHz,
CDCl3) 170.5, 167.1, 162.2, 146.2, 139.9, 139.8, 138.7, 138.0,
136.8, 132.6, 132.3, 129.9, 128.6, 128.5, 128.1, 127.9, 127.1, 119.0,
117.8, 106.9, 104.9, 103.0, 96.4, 91.3, 56.7, 52.1, 50.6, 50.4, 49.7,
22.1, 17.1, 10.8; MS (EI): 125 (100), 681 (M+, 2%). Anal. Calcd
for C39H37Cl2N3O4: C 68.62, H 5.46, N 6.16; Found: C 68.67, H
5.45, N 5.97.
(E)-Dimethyl 1,3-dibutyl-2¢-(1-methoxycarbonylethylidene)-1¢-
phenyl-1,1¢,2¢,3-tetrahydrospiro[benzimidazole-2,3¢-pyrrole]-4¢,5¢-
dicarboxylate (14b). 70%, red crystals (ethyl acetate and
petroleum ether), mp 128–129 ◦C; vmax/cm-1 1747, 1716, 1690,
1610, 1515, 1492; dH (400 MHz, CDCl3) 7.41 (t, J = 7.7 Hz, 2H),
7.33 (t, J = 7.0 Hz, 1H), 7.28 (d, J = 7.7 Hz, 2H), 6.49 (brs, 2H),
6.14 (dd, J = 5.0, 3.2 Hz, 2H), 3.68 (s, 3H), 3.46 (s, 3H), 3.14 (brs,
4H), 2.98 (s, 3H), 1.49–1.66 (m, 4H), 1.42 (s, 3H), 1.31–1.39 (m,
4H), 0.94 (t, J = 7.4 Hz, 6H); dC (100 MHz, CDCl3) 170.1, 163.3,
162.3, 148.6, 147.3, 139.6, 139.4, 129.6, 127.9, 126.4, 117.0, 115.3,
104.9, 101.6, 94.9, 52.9, 52.0, 51.0, 44.2, 30.1, 20.6, 17.0, 13.9; MS
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(E)-Methyl 1,3-di(p-bromobenzyl)-2¢-(1-methoxycarbonylethyl-
idene)-5¢-phenethyl-1¢-phenyl-1,1¢,2¢,3-tetrahydrospiro[benzimida-
zole-2,3¢-pyrrole]-4¢-carboxylate (18e). 46% from method B, yel-
low crystals (ethyl acetate and petroleum ether), mp 134–135 ◦C;
Acknowledgements
This work was supported by the National Natural Science
Foundation of China for Distinguished Young Scholars (No.
20525207), the National Natural Science Foundation of China
(No. 20832006 and 20672013), the Ministry of Science and
Technology of China (2009ZX09501-006) and Beijing Municipal
Commission of Education.
v
max/cm-1 1710, 1692, 1617, 1592, 1500; dH (400 MHz, CDCl3)
7.38–7.41 (m, 7H), 7.29 (d, J = 8.4 Hz, 4H), 7.12–7.17 (m, 3H),
6.77–6.81 (m, 4H), 6.52 (brs, 2H), 6.16 (brs, 2H), 4.27 (brs, 4H),
3.46 (s, 3H), 3.04 (s, 3H), 2.57–2.62 (m, 2H), 2.30–2.34 (m, 2H),
1.16 (s, 3H); dC (100 MHz, CDCl3) 170.7, 164.5, 160.5, 146.7,
140.4, 140.2, 138.7, 137.7, 131.1, 130.3, 129.5, 128.9, 128.6, 128.4,
128.1, 126.2, 120.8, 117.8, 112.0, 103.1, 101.6, 94.8, 52.0, 50.5,
48.6, 33.8, 28.6, 16.6; MS (ESI): 831 (M+, 45%), 833 (100), 835
(55). Anal. Calcd for C44H39Br2N3O4: C 63.40, H 4.72, N 5.04;
Found: C 63.13, H 4.95, N 4.84.
Notes and references
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(2¢E,5¢E,3¢S,4¢R) or (2¢E,5¢E,3¢R,4¢S)-Methyl 2¢-(1-methoxy-
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ospiro[1,2,4-triazole-2,3¢-pyrrolidine]-4¢-carboxylate
(19a–I).
49%, yellow crystals (ethyl acetate and petroleum ether), mp
164-166 ◦C; vmax/cm-1 1744, 1715, 1653, 1594, 1493; dH (400 MHz,
CD3COCD3, 40 ◦C) 7.72 (t, J = 3.7 Hz, 2H), 7.47 (d, J = 6.3 Hz,
2H), 7.24-7.33 (m, 13H), 6.85-6.88 (m, 1H), 6.59 (br, 2H), 4.92
(s, 1H), 4.70 (dt, J = 7.6, 2.4 Hz, 1H), 3.52 (s, 3H), 3.51 (s, 3H),
1.97-2.01 (m, 1H), 1.81-1.88 (m, 1H), 1.07 (s, 3H), 0.94 (t, J =
7.3 Hz, 3H); dC (100 MHz, CD3COCD3) 170.2, 169.5, 148.5,
143.2, 143.0, 140.5, 139.9, 137.8, 130.5, 130.4, 129.95, 129.8,
129.5, 129.49, 129.46, 129.0, 128.7, 128.1, 127.2, 120.6, 116.5,
105.0, 103.4, 94.7, 52.5, 51.8, 50.0, 22.5, 16.2, 14.8; MS (ESI): 613
(M+1). Anal. Calcd for C38H36N4O4: C 74.49, H 5.92, N 9.14;
Found: C 74.46, H 5.49, N 9.09.
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(2¢E,5¢E,3¢R,4¢R) or (2¢E,5¢E,3¢S,4¢S)-Methyl 2¢-(1-methoxy-
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ospiro[1,2,4-triazole-2,3¢-pyrrolidine]-4¢-carboxylate
(19a–II).
14%◦, yellow crystals (ethyl acetate and petroleum ether), mp 147–
149 C; vmax/cm-1 1753, 1719, 1594; dH (400 MHz, CD3COCD3)
7.41 (t, J = 7.8 Hz, 4H), 7.27–7.36 (m, 11H), 7.17 (t, J = 7.2 Hz,
2H), 7.01 (br, 2H), 6.82 (t, J = 7.2 Hz, 1H), 4.54 (dt, J = 7.6,
2.4 Hz, 1H), 4.39 (s, 1H), 3.48 (s, 3H), 3.35 (s, 3H), 1.82–1.88 (m,
1H), 1.76–1.80 (m, 1H), 1.22 (s, 3H), 0.83 (t, J = 7.3 Hz, 3H); dC
(100 MHz, CDCl3) 174.8, 173.1, 152.9, 150.9, 148.2, 145.3, 143.6,
143.3, 134.5, 134.4, 134.3, 134.1, 133.9, 133.8, 133.2, 133.0, 132.9,
132.6, 132.5, 124.7, 121.7, 108.9, 107.5, 99.3, 60.7, 56.8, 56.4, 26.6,
21.1, 18.9; MS (ESI): 613 (M+1). Anal. Calcd for C38H36N4O4: C
74.49, H 5.92, N 9.14; Found: C 74.29, H 5.74, N 9.04.
8 R. Gompper and U. Wolf, Liebigs Ann. Chem., 1979, 1979, 1406–1425.
9 B. Cetinkaya, E. Cetinkaya, J. A. Chamizo, P. B. Hitchcock, H. A.
Jasim, H. Ku¨cu¨kbay and M. F. Lappert, J. Chem. Soc., Perkin Trans.
1, 1998, 2047–2054; H. E. Winberg and D. D. Coffman, J. Am. Chem.
Soc., 1965, 87, 2776–1777; M. Regitz, J. Hocker, W. Scho¨essler, B. Weber
and A. Liedhegener, Justus Liebigs Ann. Chem., 1971, 748, 1–19; H. J.
Schoenherr and H. W. Wanzlick, Chem. Ber, 1970, 103, 1037–1046;
A. Takamizawa, K. Hirai and S. Matsumoto, Tetrahedron Lett., 1968,
9, 4027–4030; A. Takamizawa, S. Matsumoto and S. Sakai, Chem.
Pharm. Bull., 1974, 22, 293–298.
10 J.-H. Zhang and Y. Cheng, Org. Biomol. Chem., 2009, 7, 3264.
11 N. Kuhn, M. Steimann and G. Weyers, Z. Naturforsch., Teil B, 1999,
54, 427–433.
12 N. Kuhn, E. Niquet, M. Steimann and I. Walker, Z. Naturforsch, B:
Chem. Sci., 1999, 54, 1181–1187; N. Kuhn, H. Bohnen and G. Henkel,
Z. Naturforsch, B: Chem. Sci., 1994, 49, 1473–1480; S. Dummling, B.
Speiser, N. Kuhn and G. Weyers, Acta Chem. Scand., 1999, 53, 876–886;
N. Kuhn, G. Weyers, S. Dummling and B. Speiser, Phosphorus, Sulfur
Silicon Relat. Elem., 1997, 128, 45–62; W. Krasuski, D. Nikolaus and
M. Regitz, Liebigs Ann. Chem., 1982, 1982, 1451–1465.
13 M.-F. Liu, B. Wang and Y. Cheng, Chem. Commun., 2006, 1215–1217;
Y.-G. Ma and Y. Cheng, Chem. Commun., 2007, 5087–5089; Y. Cheng,
M.-F. Liu, D.-C. Fang and X.-M. Lei, Chem.–Eur. J., 2007, 13, 4282–
4292; J.-Q. Li, R.-Z. Liao, W.-J. Ding and Y. Cheng, J. Org. Chem.,
2007, 72, 6266–6269; Y. Cheng, Z.-M. Kang, Y.-G. Ma, J.-H. Peng and
M.-F. Liu, Tetrahedron, 2008, 64, 7362–7368; B. Wang, J.-Q. Li and Y.
Cheng, Tetrahedron Lett., 2008, 49, 485–489.
(E)-Methyl 2¢-(1-methoxycarbonylethylidene)-1,1¢,3,4-tetraphe-
nyl-5¢-propyl-1,1¢,2¢,4-tetrahydrospiro[1,2,4-triazole-2,3¢-pyrrole]-
4¢-carboxylate (20a). orange crystals (ethyl acetate and
petroleum ether), mp 166–168 ◦C; vmax/cm-1 1717, 1689, 1609,
1592, 1493; dH (400 MHz, CD3COCD3) 7.47–7.49 (m, 5H), 7.28–
7.33 (m, 8H), 7.09–7.18 (m, 6H), 6.73 (t, J = 7.0 Hz, 1H), 3.49 (s,
3H), 3.47 (s, 3H), 2.48–2.55 (m, 1H), 2.34–2.41 (m, 1H), 1.26 (s,
3H), 1.12–1.24 (m, 2H), 0.63 (t, J = 7.3 Hz, 3H); dC (100 MHz,
CD3COCD3) 170.3, 164.5, 164.0, 147.0, 146.0, 144.5, 139.8, 139.7,
130.4, 130.3, 130.2, 129.7, 129.6, 129.5, 129.4, 129.0, 128.9, 128.8,
127.6, 119.4, 114.9, 113.9, 102.0, 94.6, 52.6, 50.5, 28.4, 21.9, 16.3,
14.4; MS (ESI): 613 (M+1). Anal. Calcd for C38H36N4O4: C 74.49,
H 5.92, N 9.14; Found: C 74.39, H 6.04, N 9.15.
14 Y. Cheng, Y.-G. Ma, X.-R. Wang and J.-M. Mo, J. Org. Chem., 2009,
74, 850–855.
15 Crystal data for 3g: C32H28BBr2F4N3O2, M = 733.20, T = 113 K,
monoclinic, space group P21/n, a = 10.8497(12), b = 17.4399(18),
5018 | Org. Biomol. Chem., 2009, 7, 5010–5019
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◦
◦
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[R(int) = 0.0542], final R indices [I>2sigma(I)], R1 = 0.0379, wR2 =
0.0981. Crystal data for 19b-I: C39H38N4O5, M = 642.73, T = 113 K,
monoclinic, space group P 21/n, a = 11.8253(19), b = 18.626(3), c =
c = 16.2784(17) A, a = 90 , b = 98.769(3) , g = 90 , V = 3044.2(6) A ,
Z = 4, rcalcd = 1.600 g cm-3, absorption coefficient 2.723 mm-1,
reflections collected/unique 29525/7233 [R(int) = 0.0535], final R
indices [I>2sigma(I)], R1 = 0.0442, wR2 = 0.1051. Crystal data for
11d: C39H39N3O4, M = 613.73, T = 113 K, triclinic, space group
◦
◦
◦
3
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15.232(2) A, a = 90 , b = 92.810(3) , g = 90 , V = 3350.8(9) A ,
Z = 4, rcalcd = 1.274 g cm-3, absorption coefficient 0.085 mm-1,
reflections collected/unique 33818/7984 [R(int) = 0.0413], final R
indices [I>2sigma(I)], R1 = 0.0494, wR2 = 0.1289. Crystal data for
20b: C39H38N4O5, M = 642.73, T = 113 K, monoclinic, space group P
˚
P-1, a = 9.9376(10), b = 13.3618(14), c = 14.3300(16) A, a =
◦
◦
◦
3
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68.670(8) , b = 73. 901(9) , g = 72.586(8) , V = 1660.6(3) A ,
Z = 2, rcalcd = 1.227 g cm-3, absorption coefficient 0.080 mm-1,
reflections collected/unique 17084/5832 [R(int) = 0.0473], final R
indices [I>2sigma(I)], R1 = 0.0764, wR2 = 0.2439. Crystal data for
17d: C39H37Br2N3O4, M = 771.54, T = 296 K, monoclinic, space
◦
˚
21/c, a = 9.2415(9), b = 20.801(2), c = 17.0490(16) A, a = 90 , b =
◦
◦
92.631 , g = 90 , V = 3273.9(5) A , Z = 4, rcalcd = 1.304 g cm-3, absorp-
tion coefficient 0.087 mm-1, reflections collected/unique 405442/7773
[R(int) = 0.0512], final R indices [I>2sigma(I)], R1 = 0.0466, wR2 =
0.1180. CCDC 740317 (compound 3g), 740318 (compound 11d),
740319 (compound 17d), 740320 (compound 18e), 740321 (com-
pound 19b-I) and 740322 (compound 20b) contain the supplementary
crystallographic data for this paper.† These data can be obtained
free of charge from the Cambridge Crystallographic Data centre via
www.ccdc.cam.ac.uk/data_request/cif.
3
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group P◦21/c, a = 9.3172◦(1), b = 21.0352(2), c = 17.9002(2) A,
◦
3
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a = 90 , b = 96.187(1) , g = 90 , V = 3487.81(6) A , Z =
4, rcalcd = 1.469 g cm-3, absorption coefficient 2.369 mm-1, reflec-
tions collected/unique 21027/7987 [R(int) = 0.0198], final R indices
[I>2sigma(I)], R1 = 0.0440, wR2 = 0.1235. Crystal data for 18e:
C44H39Br2N3O4, M = 833.60, T = 113 K, monoclinic, space ◦group
˚
P21/n, a = 7.7608(16), b = 18.522(4), c = 26.266(5) A, a = 90 , b =
◦
◦
94.70 , g = 90 , V = 3762.8(13) A , Z = 4, rcalcd = 1.471 g cm-3, absorp-
3
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16 Y. Cheng, B. Wang, X.-R. Wang, J.-H. Zhang and D.-C. Fang, J. Org.
tion coefficient 2.203 mm-1, reflections collected/unique 38112/6631
Chem., 2009, 74, 2357–2367.
This journal is
The Royal Society of Chemistry 2009
Org. Biomol. Chem., 2009, 7, 5010–5019 | 5019
©