N-heterocyclic carbene induced cycloaddition reactions of indazoles with acetylenes to form a new ring system

Article abstract of DOI:10.1002/ejoc.200800456

Thermal decarboxylation of the mesomeric betaine 1,2-dimethylindazolium-3- carboxylate resulted in the formation of the N-heterocyclic carbene indazol-3-ylidene which deprotonated a second molecule of the betaine to give an azomethine ylide. This 1,3-dipole underwent a cycloaddition/decarboxylation sequence on treatment with ethyl or methyl 3-phenylpropiolate to give the new ring system 3,5-dihydro-2H-pyrrolo[1,2-b]indazole. By contrast, dimethyl or diethyl but-2-ynedioate (DMAD, DEAD) as the activated triple bond yielded this ring system with an ester group at the 9b-position, which originates from the acetylene derivative. Model reactions were carried out to elucidate the mechanisms of these reactions, and some trapping products of the N-heterocyclic carbene have been characterized.

Full text of DOI:10.1002/ejoc.200800456

FULL PAPER
DOI: 10.1002/ejoc.200800456
N-Heterocyclic Carbene Induced Cycloaddition Reactions of Indazoles with
Acetylenes To Form a New Ring System
Andreas Schmidt,*[a] Bohdan Snovydovych,[a] and Sascha Hemmen[b]
Keywords: Betaines / Decarboxylation / DMAD / 1,3-Dipoles / Carbenes / Cycloaddition
Thermal decarboxylation of the mesomeric betaine 1,2-di-
methylindazolium-3-carboxylate resulted in the formation of
but-2-ynedioate (DMAD, DEAD) as the activated triple bond
yielded this ring system with an ester group at the 9b-posi-
the N-heterocyclic carbene indazol-3-ylidene which depro- tion, which originates from the acetylene derivative. Model
tonated a second molecule of the betaine to give an azo-
methine ylide. This 1,3-dipole underwent a cycloaddition/de-
carboxylation sequence on treatment with ethyl or methyl 3-
phenylpropiolate to give the new ring system 3,5-dihydro-
2H-pyrrolo[1,2-b]indazole. By contrast, dimethyl or diethyl
reactions were carried out to elucidate the mechanisms of
these reactions, and some trapping products of the N-hetero-
cyclic carbene have been characterized.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2008)
have been found that form adducts 7, which are tautomers
of Breslow intermediates. The trapping of NHC 2 with α-
halo ketones results in the formation of cinnolines 8.[15]
Introduction
The broad applicability of N-heterocyclic carbenes
(NHC) of thiazole, triazole, imidazole, and imidazoline has
been impressively demonstrated since the first stable N-het-
erocyclic carbene was described.[1] They are not only excel-
lent ligands in organometallic chemistry,[2] but also versatile
organocatalysts in Stetter reactions,[3] benzoin condensa-
tions,[4] umpolung reactions,[5] enantioselective syntheses of
β-lactams by the Staudinger reaction,[6] highly diastereo-
and enantioselective additions of homoenolates to nitro-
nes,[7] and many other reactions.[8] Among these, their reac-
tions with triple bonds have also been reported.[9] Some
books and review articles dealing with the development of
N-heterocyclic carbene chemistry have been published re-
cently.[10] Less attention has been focussed on the N-hetero-
cyclic carbenes of indazole.[11] These can be generated by
decarboxylation of indazolium-3-carboxylates, which be-
long to the class of pseudo-cross-conjugated heterocyclic
mesomeric betaines.[12,13] The N-heterocyclic carbenes of
indazole undergo typical trapping reactions with sulfur to
give indazolethione 3,[13] with isocyanates to give indazol-
3-amidates 4 (X = O), with isothiocyanates to give indazole-
3-thioamidates 4 (X = S), and with protons to give indazol-
ium salts 5 (Scheme 1). Ketones form stable 1:1 adducts
6.[14] Few examples of the reactions of aromatic aldehydes
Scheme 1.
In the presence of N-heterocyclic carbene 2 and alcohols,
aromatic aldehydes undergo redox esterification reactions
to give benzoates ArCOOR and indazoline 9 (Scheme 2).[14]
Furthermore, NHC 2 effectively induces debromination
of vicinal dibromides to give alkenes (Scheme 3). The 3-
bromoindazolium ion 10 is formed as the second product
of this reaction.[15]
[a] Institute of Organic Chemistry, Clausthal University of Tech-
nology,
Leibnizstrasse 6, 38678 Clausthal-Zellerfeld, Germany
Fax: +49-5323-722858
Likewise, 1,2-dibromoethene derivatives give acetylenes
in very high yields (Scheme 4).[15]
E-mail: schmidt@ioc.tu-clausthal.de
[b] Institute of Theoretical Physics, Clausthal University of Tech-
nology,
As a continuation of an ongoing project dealing with the
chemistry of mesomeric betaines and the N-heterocyclic
Leibnizstrasse 10, 38678 Clausthal-Zellerfeld, Germany
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A. Schmidt, B. Snovydovych, S. Hemmen
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weak interactions between C-3-H2 and the carbonyl group.
A similar reaction was observed starting from ethyl 3-phen-
ylpropiolate, which gave 11b. Analogous spectroscopic re-
sults were obtained.
Scheme 2.
Scheme 5.
Formally, compounds 11a,b are tautomers of the cy-
cloadduct 11A of the azomethine ylide 12a and the acetyl-
ene derivative (Figure 1).
Scheme 3.
Figure 1. Retrosynthesis of ring system 11.
To gain some insight into the mechanism, we performed
model reactions and calculations.[17] First, we calculated the
frontier orbital profiles of the NHC and the ylide. The
HOMO and LUMO of the N-heterocyclic carbene 2 are
shown in Figure 2. As expected, the HOMO is essentially
located on the carbene lone pair, whereas the LUMO is
located over the whole π-electron system. Figure 3 presents
the frontier orbital profile of the 1,3-dipole 12a.
Scheme 4.
carbenes of indazoles, we report herein the unprecedented
reactions of the pseudo-cross-conjugated heterocyclic meso-
meric betaine 1 with activated carbon–carbon triple bonds.
Results and Discussion
Surprisingly, the reaction of indazolium-3-carboxylate 1
with methyl 3-phenylpropiolate in a mixture of toluene and
acetonitrile at 80 °C, or in pure acetonitrile at 40–50 °C,
resulted in the formation of the new ring system methyl 2H-
pyrrolo[1,2-b]indazole-1-carboxylate 11a, the structure of
which was elucidated by HSQC, HMBC, and H–H COSY
NMR spectroscopy (Scheme 5). Thus, the multiplet at δ =
6.01 ppm and the signal at δ = 75.8 ppm were assigned to
2-H and C-2, respectively. The signal of the C-3-H2 group
Figure 2. HOMO (left) and LUMO (right) of 2.
We next performed calculations for the conversion of N-
appears at δ = 68.6 ppm in the 13C NMR spectrum and heterocyclic carbene 2 into 1,3-dipole 12a (Scheme 6). The
displays all the expected couplings. Conclusions concerning dipole 12a is 18.61 kJmol–1 more stable than 2 according
the regiochemistry of this reaction were drawn from the to the calculations. However, as expected, the calculations
HMBC spectra, which revealed strong interactions of the show the intramolecular conversion 2 Ǟ 12a to have a pro-
C-2-H and C-3-H2 groups with the phenyl ring, but only hibitively large activation barrier of 180 kJmol–1.
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N-Heterocyclic Carbene Induced Cycloadditions
as reported for imidazol- and imidazolin-2-ylidenes,[9] re-
gioisomers of 11a,b would be formed, which we did not
detect in our reaction mixtures.
Figure 3. HOMO (left) and LUMO (right) of ylide 12a.
Scheme 6.
Model reactions have then been performed to examine
the intermolecular processes. No experimental evidence was
found for the in situ generated carbene 2 to deprotonate the
5-nitroindazolium salt 13 to give the 1,3-dipole 12b along
with the indazolium salt 4 (Scheme 7). In accordance with
this, a 1:1:1 mixture of 1, 13, and methyl 3-phenylpropiolate
exclusively yielded cycloadduct 11a, but no traces of the 5-
nitro derivative. Indazolium salt 4 was nonetheless isolated,
which, it was concluded, could not be the source of the 1,3-
dipoles.
Scheme 8.
Surprisingly, an analogous series of reactions starting
from the betaines 1a–c and dimethyl but-2-ynedioate
(DMAD) and diethyl but-2-yndioate (DEAD) in toluene at
80 °C or in acetonitrile/toluene at 40 °C yielded the triesters
15a–d as yellow oils (Scheme 9). The derivatives 16 and 17
were isolated as byproducts on slight modification of the
reaction conditions and careful separation of the reaction
Scheme 7.
In view of these results and the regiochemistry of the mixture.
reactions we propose the following mechanism. The unam-
Mass spectra as well as NMR spectroscopic data unam-
biguous starting point is the N-heterocyclic carbene 2, biguously indicate the presence of a third ester functionality
which forms on decarboxylation of 1 under the reaction attached to the new ring system. In accordance with H–H
1
conditions described here and which can indeed be trapped COSY, HSQC, and HMBC NMR measurements, the H
by numerous heterocumulenes and sulfur. The in situ gener- NMR signal at δ = 7.45 ppm was assigned to 9-H of 15d
ated indazol-3-ylidene 2 deprotonates betaine 1 to give the (for the numbering, cf. Scheme 5). The HMBC measure-
1,3-dipole 14 and indazolium salt 4 (Scheme 8). The former ments show a coupling with a chemical shift at δ =
species then undergoes 1,3-dipolar cycloaddition reactions 87.6 ppm, which is a quaternary atom according to DEPT
with triple bonds. Decarboxylation of 14B and protonation experiments. The connectivities and assignments are pre-
lead to the formation of the β-enaminocarbonyl chromo- sented in Figure 4. Signals of the C-3-H2 group appear at δ
phores in 11a,b. If nucleophilic attack of C-3 of the N-het- = 4.62 and 4.30 ppm, and for C-3 at δ = 65.9 ppm. The 2,5-
erocyclic carbene 2 on the activated triple bond took place, dihydropyrrole moiety is proved by couplings to C-2, C-1,
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A. Schmidt, B. Snovydovych, S. Hemmen
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Scheme 10.
We concluded that the presence of an ester group at C-
9b in 15a–d is the result of nucleophilic attack of the car-
bene atom of 2 on the carbonyl group of the acetylene de-
rivative to give adduct A (pathway A, Scheme 11). This re-
sulted in methyl or ethyl indazolium-3-carboxylate 19 after
elimination of the acetylenide moiety and prevents the sys-
tem from undergoing decarboxylation, as observed in the
formation of 11a,b. Deprotonation then yielded 1,3-dipole
18, which undergoes cycloaddition to give 15a,b. The by-
product 16 can be explained by nucleophilic attack of the
acetylenide on the iminium bond of 19. Evidence for path-
way B is the isolation of 17 from the reaction mixture. Its
formation can be rationalized by a nucleophilic attack of
the carbene atom of 2 on the triple bond to form adduct B,
formal 1,5-H shift to yield 1,3-dipole 20, and cycloaddition
to give 17.
Scheme 9.
and C-9b, and to three carbonyl signals at δ = 163.2, 163.3,
and 169.8 ppm. Coupling between the methyl group and C-
9b prove the structure as shown. All derivatives 15a–d dis-
play closely related features in the NMR spectra.
Figure 4. Some characteristic couplings in the HMBC measure-
ments of 15d.
The signal of the quaternary atom of 16 appears at δ =
70.3 ppm in the 13C NMR spectrum, and displays couplings
to 4-H and to a CH2 group of an ester in the HMBC mea-
surements. The methyl group attached to N-2 shows a small
coupling to one of the acetylenic carbon atoms and a strong
coupling to C-3. The signals of the sp carbon atoms appear
at δ = 80.3 and 80.8 ppm in the 13C NMR spectrum, and
an absorption band can be seen at 2232 cm–1 in the IR spec-
trum.
The vinylic proton of 17 was assigned to a singlet with
chemical shift δ = 6.53 ppm. According to the structure, it
couples to two ester groups, to C-9b, as well as to C-1 and
C-9a. The signals of the protons of the CH2 group of the
2,5-dihydropyrrole moiety appear at δ = 4.34 and 3.98 ppm
and display a geminal coupling constant of 17.1 Hz.
We next performed several model reactions to clarify the
origin of the ester group. We first conducted the carbene
formation in the presence of a 1:1 mixture of DMAD and
DEAD, which resulted in the formation of all possible sub-
Scheme 11.
In accordance with the proposed mechanism, 3-(ethoxy-
stitution patterns I–IV (Scheme 10), as evidenced by chro- carbonyl)-1,2-dimethyl-1H-indazolium triflate 19 could in-
matographic separation followed by electrospray ionization deed be deprotonated to azomethine ylide 18, which was
mass spectrometric analysis.
trapped by DEAD to give 15b (Scheme 12). By contrast,
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N-Heterocyclic Carbene Induced Cycloadditions
1,2-dimethyl-1H-indazolium hydrogen sulfate gave no prod-
uct under analogous reaction conditions.
Experimental Section
General: 5-Nitroindazole was prepared according to a literature
procedure.[16] 1H and 13C NMR spectra were recorded with Bruker
Digital FT-NMR Avance 400 and Avance 200 spectrometers in [D6]-
DMSO at 20 °C unless otherwise noted. Chemical shifts are re-
ported in ppm relative to internal TMS (δ = 0.000 ppm). Multi-
plicities are described by using the following abbreviations: s = sin-
glet, d = doublet, t = triplet, m = multiplet. Peak assignments were
made on the basis of HMBC, HSQC, and H–H NOESY measure-
ments. FTIR spectra were obtained with a Bruker Vector 22 in the
range of 400–4000 cm–1 (2.5% pellets in KBr). Electrospray ioniza-
tion mass spectra (ESIMS) were measured with an Agilent
LCMSD Series HP1100 spectrometer with APIES (direct inlet).
Samples were dissolved in methanol and sprayed from methanol
with a 0 V fragmenting voltage, 300 °C drying gas temperature,
4000 V capillary voltage, and 0.6 mL solvent flow unless otherwise
noted. Mass spectra were recorded with a Varian GC3900/
SAT2100T mass spectrometer. All samples were dried in vacuo at
room temp. for 5 h prior to CHN analysis. Melting points were
determined with a Boëtius melting point apparatus and are uncor-
rected. Yields were not optimized.
Scheme 12.
The effect of protic reagents was tested as follows: The
presence of a weak acid such as isoindoline-1,3-dione in the
reaction of mesomeric betaine 1 with DMAD led to the
immediate formation of the Michael adducts 20 and 21
(Scheme 13).
General Procedure for the Synthesis of the Pyrrolo[1,2-b]indazole-1-
carboxylates 11a,b and Tricarboxylates 15a,b: Under an inert gas, a
sample of 1,2-dimethyl-1H-indazolium-3-carboxylate in the solvent
specified below was treated with the acetylene derivative and then
heated at 90 °C for 2–4 h. Then, the solvent mixture was distilled
off in vacuo. The residue was purified by chromatography (silica
gel, petroleum ether/ethyl acetate = 4:1). Details are given below.
Methyl 5-Methyl-2-phenyl-3,5-dihydro-2H-pyrrolo[1,2-b]indazole-1-
carboxylate (11a): A sample of 1,2-dimethyl-1H-indazolium-3-car-
boxylate (150 mg, 0.75 mmol) in acetonitrile (0.5 mL) and toluene
(3.5 mL) was treated with methyl 3-phenylpropiolate (240 mg,
1
1.5 mmol). Yellow oil; yield 77 mg (32%). H NMR (CDCl3): δ =
7.40–7.31 (m, 6 H), 7.29–7.15 (m, 1 H), 6.93–6.85 (m, 1 H), 6.65
(d, J = 7.9 Hz, 1 H), 6.02–6.00 (m, 1 H), 4.42 (dd, J = 17.4, 2.2 Hz,
1 H), 4.29 (dd, J = 17.4, 2.4 Hz, 1 H), 3.69 (s, 3 H), 2.94 (s, 3 H)
ppm. 13C NMR (CDCl3): δ = 164.6, 151.0, 150.7, 133.5, 129.8,
128.8, 128.6, 128.5, 128.1, 128.0, 127.7, 126.6, 124.0 121.3, 110.8,
75.9, 68.5, 51.3, 43.4 ppm. IR (NaCl): ν = 3057, 2949, 2900, 1703,
˜
1482, 1436, 910 cm–1. MS (EI): m/z (%) = 306 (15), 304 (100), 247
(10), 246 (45). HRMS (ESI): calcd. for C17H19N2O6 307.1447;
found 307.1445.
Ethyl 5-Methyl-2-phenyl-3,5-dihydro-2H-pyrrolo[1,2-b]indazole-1-
carboxylate (11b): A sample of 1,2-dimethyl-1H-indazolium-3-car-
boxylate (150 mg, 0.75 mmol) in acetonitrile (0.5 mL) and toluene
(3.5 mL) was treated with ethyl 3-phenylpropiolate (262 mg,
Scheme 13.
1
1.5 mmol). Yellow oil; yield 61 mg (25%). H NMR (CDCl3): δ =
7.42–7.32 (m, 6 H), 7.21–7.17 (m, 1 H), 6.91–6.87 (m, 1 H), 6.66
(d, J = 7.8 Hz, 1 H), 6.02–6.01 (m, 1 H), 4.40 (dd, J = 17.4, 2.1 Hz,
1 H), 4.31 (dd, J = 17.4, 2.6 Hz, 1 H), 4.16 (q, J = 7.0 Hz, 2 H),
2.95 (s, 3 H), 1.17 (t, J = 7.04 Hz, 3 H) ppm. 13C NMR (CDCl3):
δ = 164.2, 151.1, 150.4, 133.7, 129.9, 128.7, 128.6 (2 C), 128.1,
127.9, 127.6, 127.1, 124.1 121.3, 110.8, 75.9, 68.7, 60.5, 43.5,
Conclusions
We have presented herein new cycloaddition reactions
between 1,3-dipoles of indazoles and activated triple bonds.
These cycloadditions are either induced by the N-heterocy-
clic carbene indazol-3-ylidene or result from an attack of
this nucleophilic carbene on the triple bond of an acetylene
14.0 ppm. IR (NaCl): ν = 3057, 2981, 2901, 1701, 1481, 1447,
˜
911 cm–1. MS (EI): m/z (%) = 320 (9), 317 (100), 245 (90), 146 (25).
derivative. The indazol-3-ylidene is generated in situ by HRMS (ESI): calcd. for C20H20N2O2 321.1603; found 321.1600.
thermal decarboxylation of the pseudo-cross-conjugated
mesomeric betaine indazolium-3-carboxylate. These reac-
Trimethyl 5-Methyl-5,9b-dihydro-3H-pyrrolo[1,2-b]indazole-1,2,9b-
tricarboxylate (15a): A sample of the betaine (95 mg, 0.5 mmol)
tions differ considerably from those reported between the
N-heterocyclic carbenes of other ring systems and activated
triple bonds.
and dimethyl but-2-ynedioate (145 mg, 1 mmol) in acetonitrile
(5 mL) was used. Yellow oil; yield 46 mg (27%). 1H NMR (CDCl3):
δ = 7.45–7.41 (m, 1 H), 7.29–7.21 (m, 1 H), 7.93 (ddd, J = 7.5, 7.4,
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A. Schmidt, B. Snovydovych, S. Hemmen
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1.0 Hz, 1 H), 6.68 (d, J = 7.9 Hz, 1 H), 4.45 (d, J = 17.2 Hz, 1 H),
4.23 (d, J = 17.2 Hz, 1 H), 3.81 (s, 3 H), 3.79 (s, 6 H), 2.95 (s, 3 H)
Reaction of Mesomeric Betaine 1 and DEAD in Toluene: A suspen-
sion of the betaine (500 mg, 2.5 mmol) and DEAD (1.05 mL,
ppm. 13C NMR (CDCl3): δ = 169.5, 163.7, 163.1, 150.8, 139.5, 6.5 mmol) in toluene (30 mL) was heated at 90–100 °C over a
136.6, 129.7, 125.3, 124.8, 121.6, 111.0, 86.6, 64.8, 53.2, 52.4 (2
period of 6 h. The solvent mixture was then removed in vacuo, and
C), 43.6 ppm. IR (NaCl): ν = 3001, 2954, 2911, 1739, 1483, 1436, the residue was purified by chromatography to yield 15b, 16, and
˜
916 cm–1. MS (EI): m/z (%) = 346 (9) [M]+, 288 (80), 257 (100). 17.
HRMS (ESI): calcd. for C17H18N2O6Na 369.1063; found 369.1062.
Ethyl 3-(3-Ethoxy-3-oxoprop-1-ynyl)-1,2-dimethyl-2,3-dihydro-1H-
C17H18N2O6 (346.3): calcd. C 58.96, H 5.24, N 8.09; found C 58.94,
indazole-3-carboxylate (16): Yellow oil; yield 87 mg (11%) 1H
H 4.70, N 8.01.
NMR (CDCl3): δ = 7.42–7.37 (m, 1 H), 7.30–7.22 (m, 1 H), 6.99–
Triethyl
5-Methyl-5,9b-dihydro-3H-pyrrolo[1,2-b]indazole-1,2,9b-
6.91 (m, 1 H), 6.68 (d, J = 7.9 Hz, 1 H), 4.39–4.28 (m, 2 H), 4.20
(q, J = 7.1 Hz, 2 H), 2.91 (s, 3 H), 2.88 (s, 3 H), 1.35 (t, J = 7.1 Hz,
3 H), 1.28 (t, J = 7.1 Hz, 3 H) ppm. 13C NMR (CDCl3): δ = 166.8,
153.1, 150.3, 129.9, 125.6, 124.0, 121.8, 110.9, 80.8, 80.3, 70.3, 62.8,
tricarboxylate (15b). Method A: A sample of the betaine (285 mg,
1.5 mmol) and acetonitrile (5 mL) were stirred at room temp. for
15 min. Then DEAD (0.29 mL, 1.6 mmol) was added. Stirring at
1
35 °C was continued for 24 h. Yellow oil; yield 128 mg (22%). H
62.2, 40.4, 38.2, 14.0, 13.9 ppm. IR (NaCl): ν = 2981, 2906, 2232,
˜
1737, 1714, 1482 cm–1. MS (EI): m/z (%) = 316 (1) [M]+, 243 (100).
HRMS (ESI): calcd. for C17H21N2O4 317.1501; found 317.1502.
C17H20N2O4 (316.4): calcd. C 64.54, H 6.37, N 8.86; found C 63.41,
H 5.70, N 7.95.
NMR (CDCl3): δ = 7.46 (dd, J = 7.6, 0.6 Hz, 1 H), 7.26–7.22 (m,
1 H), 6.92 (ddd, J = 7.6, 7.4, 0.8 Hz, 1 H), 6.66 (d, J = 8 Hz, 1 H),
4.43 (d, J = 17.2 Hz, 1 H), 4.28–4.19 (m, 7 H), 2.96 (s, 3 H), 1.32–
1.27 (m, 9 H) ppm. 13C NMR (CDCl3): δ = 169.0, 163.3, 162.9,
150.9, 138.9, 136.8, 129.6, 125.3, 125.0, 121.4, 111.0, 86.8, 64.7,
Diethyl 9b-(1,4-Diethoxy-1,4-dioxobut-2-en-2-yl)-5-methyl-5,9b-di-
hydro-3H-pyrrolo[1,2-b]indazole-1,2-dicarboxylate (17): Yellow oil;
yield 136 mg (11%). 1H NMR (C6D6): δ = 7.80–7.78 (m, 1 H),
7.00–6.96 (m, 1 H), 6.79–6.75 (m, 1 H), 6.53 (s, 1 H), 6.37 (d, J =
7.9 Hz, 1 H), 4.34 (d, J = 17.1 Hz, 1 H), 4.28–4.15 (m, 3 H), 3.97
(q, J = 7.1 Hz, 2 H), 3.91 (q, J = 7.1 Hz, 2 H), 3.84 (q, J = 7.1 Hz,
2 H), 1.05 (t, J = 7.2 Hz, 3 H), 0.90 (t, J = 7.1 Hz, 3 H), 0.86 (t, J
= 7.1 Hz, 3 H), 0.79 (t, J = 7.1 Hz, 3 H) ppm. 13C NMR (C6D6):
δ = 166.1, 164.5, 163.4, 162.8, 151.9, 151.2, 141.2, 136.7, 129.5,
127.0, 125.9, 122.4, 121.7, 111.8, 86.0, 63.4, 61.1, 61.0 (2 C), 60.5,
62.1, 61.5, 61.4, 43.6, 14.0 (3 C) ppm. IR (NaCl): ν = 2983, 2906,
˜
1734, 1482 cm–1. MS (EI): m/z (%) = 388 (5), 315 (100), 269 (44).
HRMS (ESI): calcd. for C20H25N2O6 389.1713; found 389.1937.
C20H24N2O6 (388.4): calcd. C 61.84, H 6.23, N 7.21; found C 61.83,
H 5.81, N 7.15. Method B: A suspension of 3-(ethoxycarbonyl)-1,2-
dimethyl-1H-indazolium triflate (185 mg, 0.5 mmol) was treated at
–80 °C with a 1  solution of LDA in THF (0.64 mL) and stirred
for 45 min at that temperature. Then DEAD (0.15 mL) was added
and the solution was warmed to room temp. over a period of 4 h.
A small amount of silica gel was then added, the solvent mixture
was evaporated, and the residue was purified by chromatography.
Yellow oil; yield 38 mg (20%).
43.4, 13.8, 13.7 (2 C), 13.6 ppm. IR (NaCl): ν = 2984, 2939, 2906,
˜
1728, 1479 cm–1. MS (EI): m/z (%) = 486 (14) [M]+, 314 (100),
269 (30). HRMS (ESI): calcd. for C25H31N2O8 487.2080; found
487.2088. C25H30N2O8 (486.5): calcd. C 61.72, H 6.22, N 5.76;
found C 61.06, H 5.85. N 5.34.
Triethyl 8-Chloro-5-methyl-5,9b-dihydro-3H-pyrrolo[1,2-b]indazole-
1,2,9b-tricarboxylate (15c):
A sample of the 5-chlorobetaine
(120 mg, 0.53 mmol) and DEAD (0.15 mL) were used. Pale-yellow
1
3-(Ethoxycarbonyl)-1,2-dimethyl-1H-indazolium Triflate (19):
A
oil; yield 47 mg (21%). H NMR (C6D6): δ = 8.00 (d, J = 2.2 Hz,
solution of ethyl 1,2-dimethyl-1H-indazolium-3-carboxylate (1.9 g,
0.01 mol) and a catalytic amount of nitrobenzene in xylene (30 mL)
was heated at reflux with methyl triflate (2.5 mL, 0.022 mol) over
a period of 45 min. The solvent mixture was then distilled off, and
the residue was recrystallized from acetone/diethyl ether (3:1).
White solid; m.p. 136–138 °C; yield 1.6 g (43%). 1H NMR
(CDCl3): δ = 8.36 (d, J = 8.6 Hz, 1 H), 8.03–7.89 (m, 2 H), 7.72–
7.64 (m, 1 H), 4.69 (s, 3 H), 4.64 (q, J = 7.1 Hz, 2 H), 4.41 (s, 3
H), 1.54 (t, J = 7.1 Hz, 3 H) ppm. 13C NMR (CDCl3): δ = 157.4,
130.4 (q, J = 315 Hz, 1 C), 124.5, 123.4, 122.8, 120.9, 119.7, 117.0,
1 H), 6.99 (dd, J = 8.4, 2.2 Hz, 1 H), 6.05 (d, J = 8.4 Hz, 1 H),
4.46 (d, J = 17.1 Hz, 1 H), 4.12 (d, J = 17.1 Hz, 1 H), 3.97–3.87
(m, 6 H), 2.57 (s, 3 H), 0.92–0.85 (m, 9 H) ppm. 13C NMR (C6D6):
δ = 169.5, 163.2, 162.4, 150.1, 140.9, 136.0, 129.6, 126.5, 126.2,
112.0, 86.7, 65.3, 61.9, 61.3, 61.2, 43.2, 13.6 ppm. IR (NaCl): ν =
˜
2983, 2937, 2911, 1736, 1479 cm–1. MS (EI): m/z (%) = 423 (8) [M
+ H]+, 348 (100), 303 (45). HRMS (ESI): calcd. for C20H24ClN2O6
423.1317; found 423.1323. C20H23ClN2O6 (422.9): calcd. C 56.81,
H 5.48, N 6.62; found C 57.22, H 5.16, N 6.34.
Triethyl 8-(Dimethylamino)-5-methyl-5,9b-dihydro-3H-pyrrolo[1,2-
b]indazole-1,2,9b-tricarboxylate (15d): A sample of the (dimeth-
ylamino)-substituted betaine (150 mg, 0.64 mmol), acetonitrile
(2 mL), and THF (4 mL) were used. This mixture was stirred at
room temp. for 15 min. Then DEAD (0.29 mL, 1.6 mmol) was
added, and the mixture was heated at reflux for 6 h. Workup was
110.8, 63.3, 36.0, 32.9, 12.8 ppm. IR (KBr): ν = 3109, 3059, 3023,
˜
2909, 1735, 765 cm–1. MS (EI): m/z (%) = 219 (55) [M]+, 204 (63),
159 (100). HRMS (ESI): calcd. for C12H15N2O2 219.1134; found
219.1133.
Dimethyl
2-(1,2-Dimethyl-2,3-dihydro-1H-indazol-3-yl)-3-(1,3-di-
1
carried out as described above. Yellow oil; yield 58 mg (21%). H
oxoisoindolin-2-yl)fumarate (20): A sample of 1,2-dimethyl-1H-in-
NMR (C6D6): δ = 7.45 (d, J = 2.4 Hz, 1 H), 6.59 (dd, J = 8.7, dazolium-3-carboxylate (1; 100 mg, 0.5 mmol) and phthalimide
2.4 Hz, 1 H), 6.54 (d, J = 8.7 Hz, 1 H), 4.62 (d, J = 17.1 Hz, 1 H), (75 mg, 0.5 mmol) in acetonitrile (0.5 mL) and toluene (3.5 mL)
4.30 (d, J = 17.1 Hz, 1 H), 4.06 (q, J = 7.1 Hz, 2 H), 4.05 (q, J = was treated with DMAD (150 mg, 1.05 mmol). The mixture was
7.1 Hz, 2 H), 3.90 (q, J = 7.1 Hz, 2 H), 2.85 (s, 3 H), 2.59 (s, 6 H),
0.97 (t, J = 7.1 Hz, 3 H), 0.90 (t, J = 7.1 Hz, 3 H), 0.85 (t, J =
7.1 Hz, 3 H) ppm. 13C NMR (C6D6): δ = 169.8, 163.3, 163.2, 147.6,
143.6, 139.9, 136.9, 115.4, 112.8, 110.9, 87.6, 65.9, 61.5, 61.0, 60.9,
heated at reflux for 45 min. The solvent mixture was then distilled
off, and the residue was purified by chromatography. Yellow solid;
m.p. 134–137 °C, yield 57 mg (26%). H NMR (CDCl3): δ = 7.92–
1
7.90 (m, 2 H), 7.79–7.77 (m, 2 H), 7.21–7.13 (m, 2 H), 6.92 (dt, J
= 7.5, 1.0 Hz, 1 H), 6.61 (d, J = 7.5 Hz, 1 H), 5.95 (s, 1 H), 3.80
(s, 3 H), 3.47 (s, 3 H), 2.80 (s, 3 H), 2.76 (s, 3 H) ppm. 13C NMR
(CDCl3): δ = 171.1, 166.1, 165.1, 162.8, 151.0, 149.0, 134.5, 131.8,
128.6, 127.5, 124.0, 123.0, 121.7, 121.4, 110.2, 69.6, 53.1, 51.9, 43.3,
45.8, 41.2 (2 C), 13.7 (3 C) ppm. IR (NaCl): ν = 2983, 2938, 2906,
˜
2871, 1732, 1502 cm–1. MS (EI): m/z (%) = 432 (37) [M + H]+, 431
(2) [M]+, 358 (21), 357 (100), 285 (31). HRMS (ESI): calcd. for
C22H30N3O6 432.2129; found 432.2139. C22H29N3O6 (431.5): calcd.
C 61.24, H 6.77, N 9.74; found C 60.67, H 6.25, N 8.73.
41.9 ppm. IR (KBr): ν = 3433, 2953, 1727, 1249, 722 cm–1. MS
˜
4318
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© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 4313–4319

N-Heterocyclic Carbene Induced Cycloadditions
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[11]
[12]
Acknowledgments
The Deutsche Forschungsgemeinschaft (DFG) is gratefully ac-
knowledged for financial support. Dr. Gerald Dräger (University
of Hannover, Germany) is gratefully acknowledged for measuring
the HRESIMS spectra. Prof. Peter Blöchl, Clausthal, is gratefully
acknowledged for helpful discussions.
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Received: May 7, 2008
Published Online: July 14, 2008
Eur. J. Org. Chem. 2008, 4313–4319
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4319