The reactions of 3-alkylindoles with cyclopropanes: An unusual rearrangement leading to 2,3-disubstitution

Article abstract of DOI:10.1139/v02-125

Indoles that bear an alkyl substituent in the 3-position, when treated with cyclopropanediesters, typically undergo a [3 + 2]-annulation reaction in a kinetically controlled process (1→4). If the reaction is performed at elevated temperatures for a longer period of time, a rearrangement of the putative intermediate 3 occurs in which the alkylating species undergoes a migration to the 2-position followed by loss of a proton to reform the benzopyrrole ring. The yields range from 78 to 10%. If a 3-allylindole is used in combination with a cyclopropanediester, which is further substituted with an alkenyl moiety, the product is an effective ring closing metathesis substrate and can be converted to the 1,3,3a,4,5,6-hexahydro-1H-pyrido[3,2,1-jk]carbazole system. A mechanistic discussion of the rearrangement process is presented.

Full text of DOI:10.1139/v02-125

992
The reactions of 3-alkylindoles with
cyclopropanes: An unusual rearrangement
leading to 2,3-disubstitution
Dylan B. England, Tom K. Woo, and Michael A. Kerr
Abstract: Indoles that bear an alkyl substituent in the 3-position, when treated with cyclopropanediesters, typically un-
dergo a [3 + 2]-annulation reaction in a kinetically controlled process (1J4). If the reaction is performed at elevated
temperatures for a longer period of time, a rearrangement of the putative intermediate 3 occurs in which the alkylating
species undergoes a migration to the 2-position followed by loss of a proton to reform the benzopyrrole ring. The
yields range from 78 to 10%. If a 3-allylindole is used in combination with a cyclopropanediester, which is further
substituted with an alkenyl moiety, the product is an effective ring closing metathesis substrate and can be converted to
the 1,3,3a,4,5,6-hexahydro-1H-pyrido[3,2,1-jk]carbazole system. A mechanistic discussion of the rearrangement process
is presented.
Key words: indole, cyclopropanediester, Lewis acid, ytterbium triflate, rearrangement.
Résumé : Les indoles porteurs d’un substituant alkyle en position 3, traités par des cyclopropanediesters, conduisent
généralement à une réaction d’annellation [3 + 2] par un processus sous contrôle cinétique. Si on effectue la réaction à
température élevée, pour une période prolongée, il se produit un réarrangement de l’intermédiaire putatif (3) au cours
duquel l’espèce qui provoque l’alkylation subit une migration vers la position 2 qui est suivie d’une perte d’un proton
pour reformer un noyau benzopyrrole. Les rendements varient de 78 à 10%. Si l’on utilise un 3-allylindole en
combinaison avec un cyclopropanediester substitué par une portion alcényle, le produit est un substrat résultant d’une
réaction effective de métathèse conduisant à une formation de cycle; ce substrat peut être transformé en un système
1,3,3a,4,5,6-hexahydro-1H-pyrido[3,2,1-jk]carbazole. On présente une discussion du mécanisme du processus de
réarrangement.
Mots clés : indole, cyclopropanediester, acide de Lewis, triflate d’ytterbium, réarrangement.
[Traduit par la Rédaction] England et al. 998
Introduction
For some time now, our research group has been inter-
ested in the elaboration of the indole nucleus for the pur-
poses of natural products synthesis. In particular we have
focussed on new ways to take advantage of the natural
nucleophilic character of indoles. We have found, for exam-
ple, that lanthanide triflates (in particular ytterbium triflate)
are effective in promoting the nucleophilic addition of
indoles to electron-deficient olefins (5) and cyclopropanes
(6, 7). In addition, we (5a, 6) and others (8) have reported
that high pressures are effective in further amplifying the
nucleophilic behaviour of indoles. In our more recent work
(6) we have shown that indoles with no substituents are effi-
ciently alkylated with cyclopropanediesters producing 2-
The importance of the indole moiety in biological and me-
dicinal chemistry is unarguably significant. An enormous
fraction of the bioactive alkaloids known are based on the
indole nucleus (1). Medicinal chemists have repeatedly
turned to indole-based compounds for inspiration and indeed
many indole-containing compounds are marketed as thera-
peutic agents (2). It should come as no surprise, then, that
there continues to be considerable emphasis on new methods
for the formation and the elaboration of the benzopyrrole
ring system (3). Such methods add to the toolbox of the syn-
thetic chemist and aid in the chemical synthesis of indole al-
kaloids (4).
carboalkoxy-4-indolyl butanoate esters
5 (Scheme 1).
Indoles which bear substitution at the 3-position, upon treat-
ment with the cyclopropanediester, yield the cyclopent-
annulation product 4 (7). It was noted, that if the reactions
(1J4) of substrates where where R2 = H was performed un-
der high-temperature conditions, a by-product 6 (a formal 2-
alkylation) was formed in small amounts (<5%) and in some
cases (R4 = Ph) in significant amounts.
Driven by curiosity, we subjected one example
(Scheme 2) to forcing conditions (refluxing acetonitrile,
4 days) and were able to produce 8 as the sole identifiable
product in 76% yield. By comparison, if the reaction was
Received 2 August 2001. Published on the NRC Research
Press Web site at http://canjchem.nrc.ca on 13 August 2002.
This paper is dedicated to the memory of Professor Raymond
U. Lemieux.
D.B. England, T.K. Woo, and M.A. Kerr.1 Department of
Chemistry, The University of Western Ontario, London, ON
N6A 5B7, Canada.
1Corresponding author (e-mail: makerr@uwo.ca).
Can. J. Chem. 80: 992–998 (2002)
DOI: 10.1139/V02-125
© 2002 NRC Canada

England et al.
993
Scheme 1.
Scheme 2.
Scheme 3.
performed under milder conditions (rt, 4 h), the annulation
product 7 was formed in 94% yield. Herein we detail a
mechanistic picture which explains the formation of the 2-
alkylated indoles and the factors which favour its formation
over cyclopentannulation. In some select cases the process is
synthetically useful and products can be intermediates for
the synthesis of more complex indole systems.
Results and discussion
Indoles which bear a substituent at the 3-position often
undergo further electrophilic substitution at the 2-position
(9) (Scheme 3). While appearing as a direct electrophilic at-
tack, it is widely accepted that substitution at the 2-position
of 3-substituted indoles such as 9 proceeds via further
3-alkylation to form intermediate 11 followed by a rear-
rangement to 12 and subsequent loss of a proton to form 10.
Naidoo and co-workers (10) suggest that the direct forma-
tion of the cationic intermediate 12 would be a higher en-
ergy process than via intermediate 11.
A mechanistic scenario for our observations, which illus-
trates the rearrangement, is shown in Fig. 1. Intuitive relative
energies were born out by density functional theory calcula-
tions at the B3LYP level of theory2 on I through V using R1 =
R2 = Me and R3 = H. In a first step common to the forma-
tion of both products, the indole may react with the cyclo-
propanediester to produce intermediate immonium ion II,
which can suffer two fates. In a kinetic process, ring closure
of the malonic enolate can occur to produce cyclo-
pentannulation product IV. Alternatively II may rearrange to
produce the 3° benzyllic carbocation III. Transfer of a pro-
ton in III yields the thermodynamic product V. Although the
potential energy surfaces linking the structures in Fig. 1
were not studied in detail, the geometry optimization of II
often led to the formation of IV. This suggests that a small
energetic barrier for the rearrangement process (II–IV) ex-
ists. Similarly, geometry optimization of III often lead di-
rectly to V, again suggesting a small barrier for this process.
It is interesting that the heating of compounds of type IV for
extended periods of time leads to the formation of V as well
as a small amount of the starting indole, illustrating the re-
versibility of the annulation.
2 Energies refer to those resulting from a global geometry optimization protocol. For a description of the theoretical methods employed see
the Experimental section.
© 2002 NRC Canada

994
Can. J. Chem. Vol. 80, 2002
Fig. 1. Putative mechanistic scenario for the formation and rearrangement of IV and V. Energies shown are relative to I, calculated at
the B3LYP/6-31G** level of theory using R1 = R2 = Me and R3 = H. Relative energies include zero-point vibrational energy correc-
tions.
the beneficial effects of the phenyl group while retaining
this exploitable functionality, we employed the styrenyl
Table 1.
cyclopropane 2c. In the reaction with 1,3-dimethylindole, 14
was produced in acceptable yield, while the product of the
reaction with 3-allyl-1-benzylindole produced 18 in 31%
yield. A variety of reaction conditions were explored to opti-
mize the yields. Alternative Lewis acid catalysts, solvents,
times, and temperatures offered no improvement in the
yields of the alkylation products.
In all reactions involving cyclopropane 2a and 2c, a sig-
nificant amount of compound 24 was formed (Scheme 4).
This observed product likely originates from what could be
described as a vinylogous Wagner–Meerwein rearrangement
of the intermediate immonium ion (19 or 20) to 21 or 22
which occurs in competition with the predicted rearrange-
ment.
To probe the synthetic utility of the rearrangement, a se-
Compounds such as 17 and 18 were prepared with an eye
towards ring closing metathesis (RCM) (13). Treatment of
ries of indoles (11) and cyclopropanes (12) were prepared
according to literature procedures (Table 1). In general the
17 or 18 with the commercially available Grubb’s catalyst
(13) 28, resulted in the formation of the dihydrocarbazole 25
in 85 and 96% yield, respectively (Scheme 5). Hydrogena-
tion of the double bond gave the tetrahydrocarbazole 26.
Treatment of 25 with a metallic palladium catalyst in the
presence of oxygen yielded the carbazole 27 in 67% yield.
In summary we have detailed an interesting rearrangement
reaction which results in the 2-alkylation of 3-substituted
indoles. The products may be further elaborated by ring
closing metathesis to yield tetrahydrocarbazoles which may
be of synthetic utility for the preparation of a large variety of
indole alkaloids. Efforts are underway to improve the
reactions of the indoles with the cyclopropanes were per-
formed in refluxing acetonitrile. The results are shown in Ta-
ble 2. In most cases the annulation product was formed first
and soon disappeared (by TLC) to yield the product result-
ing from 2-alkylation. Phenyl cyclopropane 2b, upon reac-
tion with 1a gave 13 in quite acceptable yield (78%). Other
cyclopropanes were less well behaved, undergoing rear-
rangements in yields that would be of questionable synthetic
utility. Our interest in having a vinylcyclopropane 2a un-
dergo this reaction stemmed from our desire to have a pen-
dant double bond in the product that could be a useful
handle for further functionalization (vide infra). To exploit
© 2002 NRC Canada

England et al.
995
Table 2.
Scheme 4.
Scheme 5.
number of conformations that might lead to a global mini-
mum, a high-temperature molecular dynamics simulation
was performed for each of II–V using the SYBYL molecu-
lar mechanics force field. Partial atomic charges for the
SYBYL calculations were obtained using the Merz–Singh–
Kollman (17) electrostatic potential charge fitting procedure
as implemented in the Gaussian 98 suite of programs (19)
from a fully optimized structure at the B3LYP/6-31G**
level (15, 16). For the purpose of generating the point
charges for the SYBYL calculations, an arbitrary conforma-
tion was utilized. Using the SYBYL potential, a 10 ns mo-
lecular dynamics simulation was performed with a time step
of 1 fs where the temperature was approximately maintained
at 1300 K by velocity rescaling every 50 000 time steps.
efficiency of the rearrangement protocol so that it may be of
general utility. Results of our efforts will be reported in due
course.
Experimental
General considerations (energy calculations)
Due to the conformational variability of the structures of
interest, the following global optimization protocol was
utilized to estimate relative energies. To generate a large
© 2002 NRC Canada

996
Can. J. Chem. Vol. 80, 2002
Two hundred structures were generated from this MD simu-
lation by sampling every 50 ps. These 200 structures were
then fully optimized at the PM3 (18) semi-empirical level
with the Gaussian 98 package. The five lowest energy struc-
tures were then fully optimized at the B3LYP/6-31G** level
with Gaussian 98. The geometry optimization of some com-
plexes often resulted in the formation of another. Conse-
quently, we report on the lowest energy structures consistent
with structures II through V. For each of the lowest energy
structures, harmonic vibrational frequency analysis at the
B3LYP/6-31G** level was performed with no constraints
for the purpose of estimating the zero-point vibrational en-
ergy. The relative energies reported in Fig. 1 are zero-point
energy corrected. It is important to note that the high-
temperature molecular dynamics was used only to generate
structures for the global optimization protocol and that the
relative energies are approprate to the zero K limit. Further-
more, the calculations have been performed on the gas-phase
molecules such that that solvation effects have been ne-
glected.
Dimethyl 2-[(3E)-2-(1,3-dimethyl-1H-indol-2-yl)-4-phenyl-
3-butenyl] malonate (14)
The general procedure above was followed using indole
1a (0.290 g, 2.0 mmol), cyclopropane 2c (0.260 g,
1.0 mmol), and Yb(OTf)3 (0.031 g, 0.05 mmol) in 3 mL
acetonitrile. The mixture was refluxed for 6 h to give, after
purification, 178 mg of 14 (44%) as an oil. IR (thin film on
1
NaCl plates ꢀ) (cm–1): 1751, 1734, 1472, 1435. H NMR
(CDCl3) ꢁ: 7.54 (d, J = 7.8 Hz, 1H), 7.34–7.18 (m, 7H), 7.11
(dt, J = 6.9, 1.2 Hz, 1H), 6.44 (dd, J = 16.2, 4.7 Hz, 1H),
6.37 (dd, J = 16.2, 4.7 Hz, 1H), 4.06 (ddd, J = 8.8, 4.9,
4.9 Hz, 1H), 3.72 (s, 3H), 3.69 (s, 3H), 3.51 (s, 3H), 3.32
(dd, J = 8.2, 6.0 Hz, 1H), 2.71–2.55 (m, 2H), 2.30 (s, 3H).
13C NMR (CDCl3) ꢁ: 169.7, 169.5, 137.1, 136.8, 134.3,
130.7, 129.9, 128.6, 128.3, 127.7, 127.5, 126.2, 121.3,
118.8, 118.3, 108.8, 52.7, 52.6, 49.8, 37.2, 32.4, 30.7, 9.3.
EI-HR-MS for C25H27NO4 calcd.: 405.1940; found:
405.1933.
Dimethyl 2-[2-(1,3-dimethyl-1H-indol-2-yl)-3-butenyl]
malonate (15)
The general procedure above was followed using indole
1a (0.290 g, 2.0 mmol), cyclopropane 2a (0.184 g,
1.0 mmol), and Yb(OTf)3 (0.031 g, 0.05 mmol) in 3 mL
acetonitrile. The mixture was refluxed for 1.5 days to give,
after purification, 72 mg of 15 (22%) as an oil. IR (thin film
General considerations (preparative chemistry)
All reactions were performed in anhydrous acetonitrile ei-
ther as purchased from VWR (DriSolv) or distilled from
CaH2. Yb(OTf)3 was used as the hydrate as purchased from
Aldrich. TLC analysis was performed on E. Merck glass
plates precoated with silica gel 60 F254. Flash column chro-
matography (FCC) was performed on silica gel purchased
1
on NaCl plates ꢀ) (cm–1): 1751, 1734, 1472, 1434. H NMR
(CDCl3) ꢁ: 7.51 (d, J = 7.9 Hz, 1H), 7.25 (d, J = 7.9 Hz,
1H), 7.19 (t, J = 7.9 Hz, 1H), 7.09 (t, J = 7.9 Hz, 1H), 6.06
(ddd, J = 17.2, 10.2, 5.4 Hz, 1H), 5.17 (dd, J = 10.4, 1.2 Hz,
1H), 5.07 (dd, J = 17.2, 1.2 Hz, 1H), 3.91–3.85 (m, 1H),
3.72 (s, 3H), 3.65 (s, 3H), 3.49 (s, 3H), 3.27 (t, J = 8.3,
6.2 Hz, 1H), 2.60–2.46 (m, 2H), 2.25 (s, 3H). 13C NMR
(CDCl3) ꢁ: 169.6, 169.5, 138.1, 137.1, 134.2, 128.3, 121.2,
118.7, 118.2, 115.7, 108.7, 108.5, 52.6, 52.5, 49.7, 37.8,
31.7, 30.6, 9.1. EI-HR-MS for C19H23NO4 calcd.: 329.1627;
found: 329.1628.
1
from Silicycle. H NMR spectra were recorded at 400 or
600 MHz. 13C NMR spectra were recorded at 100 or
125 MHz. Mass spectra (EI) were recorded using an ioniz-
ing voltage of 70 eV.
General procedure for the Yb(OTf)3-catalyzed 2-
alkylation of indoles with cyclopropanediesters
The indole (2 equiv), cyclopropane (1 equiv), and
Yb(OTf)3 (5 mol%) were charged into a dry flask equipped
with a stirring bar. Acetonitrile was added via syringe and
the mixture stirred under argon for the indicated time at re-
flux. The solvent was removed in vacuo and the residue pu-
rified by FCC on silica using mixtures of EtOAc–hexanes.
Dimethyl 2-[2-(1-benzyl-3-methyl-1H-indol-2-yl)-3-
butenyl] malonate (16)
The general procedure above was followed using indole
1b (0.442 g, 2.0 mmol), cyclopropane 2a (0.184 g,
1.0 mmol), and Yb(OTf)3 (0.031 g, 0.05 mmol) in 3 mL
acetonitrile. The mixture was refluxed for 1.5 days to give,
after purification, 73 mg of 16 (18%) as an oil. IR (thin film
Diethyl 2-[2-(1,3-dimethyl-1H-indol-2-yl)-2-phenyl ethyl]
malonate (13)
1
on NaCl plates ꢀ) (cm–1): 1751, 1734, 1636, 1466, 1453. H
The general procedure above was followed using indole
1a (0.290 g, 2.0 mmol), cyclopropane 2b (0.262 g,
1.0 mmol), and Yb(OTf)3 (0.031 g, 0.05 mmol) in 3 mL
acetonitrile. The mixture was refluxed for 1.5 days to give,
after purification, 318 mg of 13 (78%) as an oil. IR (thin
film on NaCl plates ꢀ) (cm–1): 1747, 1730, 1601, 1472,
NMR (CDCl3) ꢁ: 7.57–7.55 (m, 1H), 7.26–7.09 (m, 6H),
6.93 (d, J = 7.4 Hz, 2H), 5.94 (ddd, J = 17.2. 10.3, 5.9 Hz,
1H), 5.33 (AB, 2H), 5.03 (d, J = 10.3 Hz, 1H), 4.87 (d, J =
17.2 Hz, 1H), 3.76–3.71 (m, 1H), 3.68 (s, 3H), 3.51 (s, 3H),
3.27 (dd, J = 8.4, 6.0 Hz, 1H), 2.50–2.42 (m, 1H), 2.37–2.27
(m, 1H), 2.31 (s, 3H). 13C NMR (CDCl3) ꢁ: 169.6, 169.4,
138.1, 137.6, 136.8, 134.5, 128.8, 128.6, 127.0, 125.8,
121.6, 119.1, 118.2, 115.8, 109.4, 108.8, 52.6, 52.4, 49.4,
46.8, 38.1, 31.8, 9.4. EI-HR-MS for C25H27NO4 calcd.:
405.1940; found: 405.1937.
1
1447. H NMR (CDCl3) ꢁ: 7.57 (d, J = 8.1 Hz, 1H), 7.31–
7.17 (m, 7H), 7.13–7.09 (m, 1H), 4.59–4.55 (m, 1H), 4.26–
4.16 (m, 2H), 4.03–3.95 (m, 1H), 3.91–3.85 (m, 1H), 3.41
(s, 3H), 3.31–3.28 (m, 1H), 3.02–2.94 (m, 1H), 2.81–2.74
(m, 1H), 2.33 (s, 3H), 1.26 (t, J = 7.2 Hz, 3H), 1.13 (t, J =
7.2 Hz, 3H). 13C NMR (CDCl3) ꢁ: 169.3, 169.2, 141.4,
137.1, 135.0, 128.5, 128.3, 127.3, 126.5, 121.3, 118.7,
118.4, 109.3, 108.7, 61.5, 61.5, 50.2, 38.7, 31.6, 30.5, 14.0,
13.9, 9.3. EI-HR-MS for C25H29NO4 calcd.: 407.2097;
found: 407.2097.
Dimethyl 2-[2-(3-allyl-1-benzyl-1H-indol-2-yl)-3-butenyl]
malonate (17)
The general procedure above was followed using indole
1c (0.247 g, 1.0 mmol), cyclopropane 2a (0.184 g,
© 2002 NRC Canada

England et al.
997
1.0 mmol), and Yb(OTf)3 (0.031 g, 0.05 mmol) in 3 mL
acetonitrile. The mixture was refluxed for 1.5 days to give,
after purification, 69 mg of 17 (16%) as an oil. IR (thin film
on NaCl plates ꢀ) (cm–1): 1751, 1734, 1636, 1465, 1453,
H2 gas. The mixture was then stirred under a balloon of H2
at ambient temperature for 3 h. The reaction mixture was
then filtered over a pad of Celite, rinsed with THF, and sub-
jected to flash chromatography on silica gel (EtOAc–hex-
anes as the eluent) to yield 0.079 g (88%) of 26 as an oil. IR
(thin film on NaCl plates ꢀ) (cm–1): 1750, 1734, 1480, 1453,
1
1435. H NMR (CDCl3) ꢁ: 7.59 (d, J = 6.8 Hz, 1H), 7.27–
7.08 (m, 6H), 6.93 (d, J = 7.2 Hz, 2H), 6.05–5.90 (m, 2H),
5.38 (AB, 2H), 5.11–5.01 (m, 3H), 4.91 (d, J = 17.5 Hz,
1H), 3.79–3.73 (m, 1H), 3.70 (s, 3H), 3.53 (s, 3H), 3.59–
3.49 (m, 2H), 3.28 (dd, J = 8.5, 6.0 Hz, 1H), 2.53–2.42 (m,
1H), 2.32–2.25 (m, 1H). 13C NMR (CDCl3) ꢁ: 169.6, 169.3,
137.9, 137.9, 137.3, 137.1, 135.2, 128.6, 128.1, 127.0,
125.8, 121.7, 119.2, 118.8, 116.0, 114.8, 111.0, 109.6, 52.6,
52.4, 49.4, 47.0, 37.9, 32.0, 29. EI-HR-MS for C27H29NO4
calcd.: 431.2097; found: 431.2101.
1
1435. H NMR (CDCl3) ꢁ: 7.51 (d, J = 8.3 Hz, 1H), 7.27–
7.06 (m, 6H), 6.91 (d, J = 7.9 Hz, 2H), 5.43 (s, 2H), 3.69 (s,
6H), 3.56 (dd, J = 11.3, 3.8 Hz, 1H), 2.88–2.83 (m, 1H),
2.77–2.65 (m, 2H), 2.35 (ddd, J = 13.5, 11.4, 1.6 Hz, 1H),
2.06 (ddd, J = 15.2, 11.7, 1.6 Hz, 1H); 1.93–1.78 (m, 4H).
13C NMR (CDCl3) ꢁ: 169.7, 169.6, 138.4, 137.4, 137.0,
128.5, 127.2, 126.9, 125.8, 121.3, 118.9, 118.0, 110.1,
109.6, 52.7, 52.6, 49.5, 45.9, 32.3, 29.5, 25.8, 20.9, 18.1. EI-
HR-MS for C25H27NO4 calcd.: 405.1940; found: 405.1954.
Dimethyl 2-[(3E)-2-(3-allyl-1-benzyl-1H-indol-2-yl)-4-
phenyl-3-butenyl] malonate (18)
Acknowledgements
The general procedure above was followed using indole
1c (0.400 g, 1.6 mmol), cyclopropane 2c (0.443 g, 1.7 mmol),
and Yb(OTf)3 (0.050 g, 0.08 mmol) in 7 mL acetonitrile.
The mixture was refluxed for 1 day to give, after purifica-
tion, 255 mg of 18 (31%) as an oil. IR (thin film on NaCl
We wish to thank the Natural Sciences and Engineering
Research Council (NSERC), The Ontario Ministry of Sci-
ence and Technology, and MedMira Laboratories for fund-
ing. We also wish to thank SHARCNET, The Canadian
Foundation for Innovation, and the Ontario Innovation Trust
for the support of computing resources. D.B.E. is the recipi-
ent of an Ontario Graduate Scholarship.
1
plates ꢀ) (cm–1): 1750, 1734, 1495, 1466, 1453. H NMR
(CDCl3) ꢁ: = 7.59 (d, J = 7.2 Hz, 1H), 7.28–7.04 (m, 11H),
6.93 (d, J = 7.7Hz, 2H), 6.26 (dd, J = 15.7, 6.4 Hz, 1H),
6.10 (d, J = 15.7 Hz, 1H), 6.06–5.97 (m, 1H), 5.42 (AB,
2H), 5.10–5.02 (m, 2H), 3.95–3.90 (m, 1H), 3.68 (s, 3H),
3.66–3.49 (m, 2H), 3.55 (s, 3H), 3.32 (dd, J = 8.5, 6.0 Hz,
1H), 2.58–2.50 (m, 1H), 2.40–2.33 (m, 1H). 13C NMR
(CDCl3) ꢁ: 169.6, 169.3, 137.9, 137.3, 137.1, 136.7, 135.6,
131.1, 129.5, 128.7, 128.4, 127.4, 127.1, 126.1, 125.9,
121.7, 119.3, 118.8, 115.0, 111.0, 109.7, 109.5, 52.7, 52.5,
49.5, 47.1, 37.6, 32.8, 29.2. EI-HR-MS for C33H33NO4
calcd.: 507.2410; found: 507.2413.
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Dimethyl 2-[(9-benzyl-4,9-dihydro-1H-carbazole-1-
yl)methyl]malonate (25)
Indole 18 (0.255 mg, 0.50 mmol) and Grubbs’ catalyst 28
(21 mg, 0.025 mmol) were charged into a dry flask equipped
with a stirring bar. Dichloromethane was added via syringe
and the mixture stirred under argon at room temperature for
4 h. The mixture was then concentrated in vacuo and puri-
fied by column chromatography (EtOAc–hexanes as the
eluent) to yield 0.195 g (96%) of 25 as a an oil. IR (thin film
on NaCl plates ꢀ) (cm–1): 1751, 1733, 1466, 1453, 1435.
1H NMR (CDCl3) ꢁ: 7.52 (d, J = 8.2 Hz, 1H), 7.26–7.07 (m,
6H), 6.95 (d, J = 7.8 Hz, 2H), 6.17–6.15 (m, 1H), 5.77–5.73
(m, 1H), 5.45 (d, J = 17.2 Hz, 1H), 5.32 (d, J = 17.2 Hz,
1H), 3.68 (s, 3H), 3.68–3.63 (m, 2H), 3.48–3.44 (m, 1H),
3.36 (t, J = 7.0 Hz, 1H), 3.14 (s, 3H), 2.47 (ddd, J = 12.9,
6.6, 6.6 Hz, 1H), 2.36 (ddd, J = 14.1, 7.0, 3.3 Hz, 1H).
13C NMR (CDCl3) ꢁ: 170.2, 169.2, 138.1, 137.2, 133.3,
128.7, 127.5, 127.1, 126.6, 126.5, 125.9, 121.6, 119.1,
118.1, 109.6, 109.3, 52.6, 52.2, 47.5, 46.7, 34.0, 32.0, 23.7.
EI-HR-MS for C25H25NO4 calcd.: 403.1784; found: 403.1787.
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