Ring closing metathesis strategies towards functionalised 1,7-annulated 4,6-dimethoxyindoles

Article abstract of DOI:10.1016/j.tet.2011.04.019

A ring closing metathesis approach has been used to prepare a novel range of indoles 1,7-annulated with nitromethyl and lactone functionalised medium-sized rings. Initial studies into the preparation of lactam functionalised rings are also discussed.

Full text of DOI:10.1016/j.tet.2011.04.019

Tetrahedron 67 (2011) 4093e4102
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Ring closing metathesis strategies towards functionalised 1,7-annulated
4,6-dimethoxyindoles
*
Kasey Wood, David StC Black, Naresh Kumar
School of Chemistry, The University of New South Wales, Anzac Parade, Sydney, NSW 2052, Australia
a r t i c l e i n f o
a b s t r a c t
Article history:
A ring closing metathesis approach has been used to prepare a novel range of indoles 1,7-annulated with
nitromethyl and lactone functionalised medium-sized rings. Initial studies into the preparation of lactam
functionalised rings are also discussed.
Received 6 January 2011
Received in revised form 24 March 2011
Accepted 4 April 2011
Ó 2011 Elsevier Ltd. All rights reserved.
Available online 13 April 2011
Keywords:
Indole
1,7-Annulated
Ring closing metathesis
Medium-sized ring
1. Introduction
OH
NH
H
The indole moiety is found extensively throughout terrestrial
and aquatic natural products. Indole alkaloids have been subjected
to intensive scrutiny over the years due to the frequency and variety
of physiological activities displayed by these compounds. Mean-
while, many natural bioactive products possess functionalised
medium-sized rings. Naturally occurring medium-sized lactones,
for example, have shown anticancer1 and antibiotic2 activities
while medium-sized lactams have potential applications in
pharmaceuticals,3e5 materials6,7 and catalysis.8
H
N
O
COOH
N
N
N
H
O
O
N
1
H
2
3
H
N
O
O
N
Indoles annulated with medium-sized rings are an interesting
class of compounds that have been found both in nature and
throughout chemical synthesis. Natural examples include affinine 1
and tronocarpine 2, which have been isolated from Taber-
naemontana hystrix9 and Tabernaemontana corymbosa,10 re-
spectively, as well as clavicipitic acid 3, which is a derailment
product of normal ergot metabolism.11 Synthetic examples include
iprindole 4, which has been clinically used as an antidepressant12
and the macrocyclic bisindolylmaleimides 5, which are currently
being developed to treat diabetic complications.13
N
N
N
O
5
R
4
H
N
N
O
N
O
O
R
N
N
N
H
n = 1-4
n = 1-4
However, there are only limited reports in the literature of indoles,
which are 1,7-annulated with medium-sized rings, despite their po-
tential for interesting bioactivities. The indolocarbazoles 6 are cyclin-
dependent kinase inhibitors,14 while the 1,7-annulated ondanstron
derivatives 7 display a high affinity for the serotonin 5-HT3 receptor.15
7
6
Synthetic approaches towards these structures are currently
limited. One approach entails Stille coupling of 7-bromoindole 8
with tributylvinyltin followed by N-alkylation with 5-bromo-
pentene and subsequent ring closing metathesis of precursor 10
(Scheme 1).14
* Corresponding author. Tel.: þ61 2 9385 4698; fax: þ61 2 9385 6141; e-mail
address: n.kumar@unsw.edu.au (N. Kumar).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.04.019

4094
K. Wood et al. / Tetrahedron 67 (2011) 4093e4102
R1
OMe
R1
OMe
R1
OMe
a
b
c
a
b
N
H
N
H
N
N
R2
R2
R2
78-91 %
MeO
67-94
%
MeO
Br
N
N
N
MeO
H
H
CHO
16
CHO
17
15
8
9
10
11
Scheme 1. (a) Tributylvinyltin, PdPh2Cl2, LiCl, PPh3, DMF, 90 ꢀC (b) NaH, 5-bromo-
pentene, DMF, 0 ꢀC (c) Grubbs’ catalyst, DCM, rt.
c
65-92 %
R1
OMe
R1
OMe
R1
OMe
Alternatively, the synthesis can begin from benzazepine 12 and
ethylbromopyruvate followed by ring closure in the presence of
magnesium chloride to form derivative 14 as reported by van
Wijngaarden et al. (Scheme 2).15
d
e
R2
R2
R2
17-99 %
MeO
40-61 %
MeO
N
N
N
MeO
O2N
n=1,2
NO2
NO2
n=1,2
18
COOC2H5
COOC2H5
b
19 n = 1
20 n = 2
21 n = 1
22 n = 2
a
NH
N
N
a R1 = Ph, R2 = Ph
b R1 = 4-BrC6H4, R2 = H
c R1 = 4-ClC6H4, R2 = H
d R1 = 4-MeC6H4, R2 = H
O
n = 1-2
n = 1-2
n = 1-2
Scheme 3. (a) POCl3, DMF, rt, 2 h (b) allyl bromide, KOH, DMSO, rt, 1 h (c) CH3NO2,
ammonium acetate, i-PrOH, reflux, 3 h (d) allylmagnesium bromide, THF, rt, 3 h (e)
Grubbs’ catalyst, toluene, reflux, 4 h.
12
13
14
Scheme 2. (a) BrCH2COCOOC2H5, THF (b) MgCl2, methylcellosolve.
However, neither of these approaches offers a ready capacity to
introduce functionality into the medium-sized ring, which is an
important goal given the high chemical functionality displayed in
the natural examples. Our interest therefore lay in the development
of versatile approaches to indoles 1,7-annulated with functional-
ised medium-sized rings. In particular, an alternative approach to
cycloalkane rings and strategies towards lactone and amide func-
tionalised rings were targeted.
In addition to the well known difficulties inherent in building
eight to eleven-membered rings,16,17 strategies towards indoles 1,7-
annulated with medium-sized rings appear to be hampered by the
lack of indole reactivity at C7. It has been previously shown, how-
ever, that indole C7 reactivity can be enhanced by the strategic
placement of methoxy substituents on the benzenoid ring18 and we
have previously reported the C7 formylation, acylation, halogena-
tion and nitration of a range of 4,6-dimethoxyindoles.19e21 These
4,6-dimethoxyindoles subsequently facilitated the development of
simple and versatile routes to various indoles 1,7-annulated with
five- and six-membered rings19,22e25 and were therefore selected
as the starting point for this work.
tetrahydrofuran. The reaction mixture was quenched with aqueous
ammonium chloride after 2e3 h and the resulting solution
extracted with dichloromethane to give the eight-membered ring
closing metathesis precursors 19aed as low melting solids. The
corresponding nine-membered ring precursors 22bed were pro-
duced upon treatment of indoles 18bed with butenylmagnesium
bromide in dry tetrahydrofuran. These reactions were noticeably
slower, with the Michael addition typically requiring a large excess
of the Grignard reagent and 3 days to reach completion. Precursors
20bed were obtained as oils in 17e54% yields.
Ring closing metathesis of Michael adducts 19aed and 20bed
afforded the indole fused eight-membered rings 21aed and indole
fused nine-membered rings 22bed, respectively. Ring closing me-
tathesis was achieved by refluxing in dry, degassed toluene in the
presence of second generation Grubbs’ catalyst for 4 h.
The corresponding synthesis of 10- and 11-membered ring
systems was attempted via extension of the alkyl chain in the
N-alkylation step. The 1-pentene and 1-hexene derivatives of 17
readily underwent the Henry reaction and subsequent Michael
addition, however, the ring closing metathesis proved problematic
and only starting materials were recovered after heating at reflux
for 3 days. Direct ring closure of the 1-pentene derivative of 18 was
also examined but again no reaction was apparent, likely due to the
nitro group inhibiting the catalyst turnover.
2. Results and discussion
2.1. Synthesis of cycloalkane fused indoles
Indoles 1,7-annulated with cycloalkanes bearing a nitroalkyl moi-
ety were synthesised as shown in Scheme 3.26 Formylation of indoles
15aed was performed at room temperature using 1 equiv of the
Vilsmeier reagent. With the C2 position blocked, the reaction of indole
15a occurred exclusively at C7. Indoles 15b,c contain electron with-
drawing groups at the 40-position, which deactivates the C2 position,
thus only the C7-isomers 16b,c were obtained. Methylphenylindole
15d displayed a stronger C2 electrophilic reactivity than the haloge-
nated indoles. In the presence of 1 equiv of the Vilsmeier reagent the
reaction was regioselective for C7 at room temperature, forming
compound 16d. In the presence of an excess of Vilsmeier regent, the
2,7-di-formyl product was formed at room temperature instead.
Treatment of indole-7-carbaldehydes 16aed at room temperature
with potassium hydroxide and allyl bromide in dimethylsulfoxide for
1 h afforded N-allyl derivatives 17aed in high yields. The corre-
2.2. Synthesis of lactone fused indoles
It was envisaged that indole fused lactones of type 23 could be
prepared via the ring closing metathesis of precursor 24, which in
turn would be assessable through alkylation of the corresponding
indole-7-carboxylic acids 25. Previous work by Black et al.19,27 in-
dicated indole-7-carboxylic acids 25 could be obtained through
trihaloacetylation of indoles 15 with trifluoroacetic anhydride fol-
lowed by treatment with hydroxide ions (Scheme 4).
Trifluoroacetylation of indoles 15b and 15d was performed by
stirring at room temperature for 2 h with trifluoroacetic anhydride
in tetrahydrofuran. In contrast to the literature precedent, the
N-trifluoroacetylindole isomer was produced in addition, or even in
preference, to the desired 7-trifluoroacetylindoles 26b,d. The effi-
ciency of the reaction was therefore enhanced by the prior in-
troduction of an N1 blocking group, with the N-allyl derivatives of
15b and 15d undergoing regioselective C7 trifluoroacetylation in
good yields. However, subsequent conversion of the N-allyl de-
rivatives of 26b,d to the corresponding acids proved problematic.
spondingb-nitrostyrenes18aedwerethenproducedin 65e92% yields
upon refluxing with nitromethane and ammonium acetate for 3 h.
Michael addition of allylmagnesium bromide to nitroalkenes
18aed was conducted under inert conditions in dry

K. Wood et al. / Tetrahedron 67 (2011) 4093e4102
4095
R1
R1
OMe
OMe
23a. Two methoxygroups were present as singlets at
the H5 proton appeared as a singlet at
appeared as multiplets at 7.14 and 7.29. In addition, two signals,
integrating for 1H each, appeared at 5.63 and 6.03, which was con-
d
3.74 and
d
3.96,
R1
OMe
d
6.29 and two phenyl rings
R2
R2
R2
d
d
N
N
N
MeO
MeO
MeO
H
d
O
O
NH
O
NH
sistent with a eCH¼CHe group. These signals had a doublet of a triplet
splitting pattern, which suggested that they each possessed a CH2
neighbour, however, the only other signal present in the spectrumwas
HN
25
23
24
a multiplet at d 4.65, which integrated for 1H. Similarly, the DEPT135
experiment did not reveal the presence of any CH2 groups.
a R1 = Ph, R2 = Ph
b R1 = 4-BrC6H4, R2 = H
c R1 = 4-ClC6H4, R2 = H
d R1 = 4-MeC6H4, R2 = H
High-resolution mass spectrometry showed the product had an
m/z of 426.1705, which was consistent with C27H24NO4 for the
expected structure 23a. It was therefore conjectured that the flex-
ibility of the nine-membered ring was influencing the relaxation
time of the CH2 groups, resulting in an unusual NMR spectrum. A
variable temperature 1H NMR experiment was subsequently con-
ducted. Heating the sample to 330 K resulted in a very broad peak
R1
R1
OMe
OMe
R2
R2
N
N
H
MeO
MeO
H
15
O
CCl3
26
Scheme 4.
appearing at
d
4.25. As the sample was cooled to 230 K this peak
4.65. Despite
sharpened and merged with the original signal at
d
The reactions were very low yielding and the isolated solids were
impure even after optimisation.
the appearance of a missing signal in the variable temperature
experiment, the integration of the peaks still lacked two hydrogens
of the proposed structure 23a. Final confirmation of structure 23a
was therefore obtained through X-ray crystallography (Fig. 1).
An alternate strategy was therefore to bypass the formation of
the carboxylic acid intermediate and to form the ester directly from
the trihaloacetylindole. Literature reports have shown that tri-
fluoromethyl ketones cannot be directly converted into esters but
that this can be achieved in a single step from the related tri-
chloromethyl ketones.27,28
In contrast to trifluoroacetic anhydride, trichloroacetic anhydride
does not react with indoles 15 even under vigorous conditions.27 Tri-
chloroacetylindole derivatives 27 were therefore formed viatreatment
with trichloroacetyl chloride. Heating 2,3-disubstituted indole 15a at
reflux with a five-times excess of trichloroacetyl chloride successfully
afforded trichloroacetylindole 27a as a single product. Similar treat-
ment of the 3-substituted indoles 15b,c afforded four compounds
according to thin layer chromatography analysis. In accordance with
the literature, the major reaction products were the 7-tri-
chloroacetylindoles 27b,c and the isomeric 2-trichloroacetylindoles.
The minor products, present only in trace amounts, were identified as
the N- and 2,7-disubstituted isomers.
Alcoholysis of 7-trichloroacetylindoles 27aec was achieved by
heating at reflux in tetrahydrofuran for 2 h with allyl alcohol and
potassium hydroxide. The indole-7-carboxylic esters 28aec were
obtained in 79e86% yield. Ring closing metathesis precursors 24aec
were subsequently synthesised by N-alkylationofindoles 28aec with
allyl bromide in a basic solution of dimethylsulfoxide (Scheme 5).
Ring closing metathesis of precursor 24awas performed by heating
under reflux for 5 h in a dry, degassed solution of toluene with
5e10 mol % of second generation Grubbs’ catalyst. The 1H NMR spec-
trum of the resulting solid was not indicative of the target structure
Fig. 1. OTREP diagram of compound 23a.29
Ring closing metathesis of indoles 24b,c led to the formation of
the corresponding esters 23b,c. In contrast to the 1H NMR spectrum
of compound 23a, the spectra of analogues 23b,c contained all the
expected signals. The 1H NMR spectrum of indole 23c was char-
acteristic for these compounds, displaying singlets at
3.84 (3H each) corresponding to the methoxy groups and dou-
R1
OMe
d
3.79 and
R1
OMe
R1
OMe
d
R2
R2
blets at
d
7.29 and 7.43 (each 2H, J¼8.2 Hz) corresponding to the p-
a
N
b
R2
MeO
N
H
MeO
14-65 %
substituted aryl protons. H8 and H11 were present as singlets (1H
each) at 6.83 and 6.28, respectively, while H3 and H6 appeared
as doublets at 4.72 (2H, J¼4.9 Hz). Fi-
4.65 (2H, J¼2.3 Hz) and
nally, H4 and H5 appeared as doublet of triplets at
5.49 (1H, J¼3.8
and 15.5 Hz) and
5.89 (1H, J¼5.3 and 15.5 Hz).
79-86%
H
N
MeO
O
O
H
d
d
Cl3C
O
15
27
28
d
d
d
c
62-92 %
d
a R1 = Ph, R2 = Ph
b R1 = 4-BrC6H4, R2 = H
c R1 = 4-ClC6H4, R2 = H
R1
OMe
R1
OMe
d
2.3. Attempted synthesis of amide fused indoles
R2
R2
15-78 %
N
N
MeO
MeO
It was envisaged that amide analogues of structure 23 could be
prepared through the treatment of trichloroacetylindole de-
rivatives 27 with allyl amine followed by N-alkylation and ring
closing metathesis. Indole-7-carboxamide 29 was successfully
produced in 88% yield by heating the parent indole 27a at reflux
with allyl amine in tetrahydrofuran for 2 h (Scheme 6).
O
O
O
O
23
24
Scheme 5. (a) Trichloroacetyl chloride, DCE, reflux, 3 h (b) allyl alcohol, THF, reflux, 2 h
(c) allyl bromide, KOH, DMSO, rt, 4 h (d) Grubbs’ catalyst, toluene, reflux, 5 h.

4096
K. Wood et al. / Tetrahedron 67 (2011) 4093e4102
OMe
OMe
Ph
OMe
Ph
Ph
Ph
Ph
a
Ph
N
N
MeO
MeO
N
MeO
H
H
73 %
O
NH
O
CCl3
O
NH
27a
29
b
30
47 %
OMe
Ph
OMe
OMe
Ph
Ph
N
Ph
Ph
Ph
N
MeO
c
MeO
N
MeO
O
82 %
N
O
N
O
N
31
33
32
Scheme 6. (a) Allyl amine, THF, reflux, 2 h (b) allyl bromide, KOH, DMSO, rt, 3 h (c)
Grubbs’ catalyst, toluene, reflux, 5 h.
Subsequent N-alkylation proved to be problematic. When indole
29 was treated with potassium hydroxide and allyl bromide in
dimethylsulfoxide for 3 h, alkylation occurred at both the amide and
N1 positions to produce indole31 in preference to the target precursor
30. Conversely, heating indole 29 at reflux in acetone with allyl bro-
mideandpotassiumcarbonateresultedonlyinrecoveryofthestarting
material. Attention consequently turned to the use of a secondary
amine for the preparation of carboxamides, with a benzyl group being
initially selected as a blocking group because it could later be removed
through hydrogenation. The reaction of indole 27a with N-benzyl-N-
allylamine was investigated but only a trace amount of a product was
observed, even under vigorous conditions and in the presence of
a large excess of the amine. The reaction of indole 27a with the less
bulky N-methyl-N-allylamine was also examined, but again only
a trace amount of product wasapparent by thin layerchromatography.
Ring closing metathesis of the over alkylated product 31 was
performed by heating at reflux for 5 h in a dry, degassed solution of
toluene with 5e10 mol % of second generation Grubbs’ catalyst,
affording a single product as an off white solid. It was anticipated
that the five-membered ring structure 33 would be favoured over
the desired nine-membered fused system 32, however, Basu and
Waldmann have reported a diene-ene ring closing metathesis re-
action that gave a 2:3 ratio of five- and seven-membered cyclic
ethers.30 The 1H NMR spectrum showed 11 alkyl protons, while four
CH2 groups appeared in the DEPT135 13C NMR experiment, in-
dicating that ring closure had occurred. However, differentiating
between structures 33 and 32 using 1D and 2D NMR was difficult
due to the CH2 groups having diastereotopic protons, which over-
lapped with the other alkyl signals. Structure confirmation was
therefore obtained through X-ray crystallography, which showed
that the five-membered ring compound 33 was produced (Fig. 2).
Fig. 2. ORTEP diagram of amide 33.29
a Mattson Genesis Series FTIR spectrophotometer as KBr disks.
Ultraviolet spectra were measured using a Varian Cary 100 spec-
trophotometer. 1H and 13C NMR spectra were obtained in the des-
ignated solvents on a Bruker DPX 300 or a Bruker AVANCE DMX
600 spectrometer as designated. Low resolution ESIþ mass spectra
were recorded on a VG Quatro mass spectrometer at 70eV ioniza-
tion voltage and 200 ꢀC ion source temperature at the Bioanalytical
Mass Spectrometry unit, UNSW. High-resolution mass spectrome-
try was performed by the Mass Spectrometry unit at the University
of Otago, New Zealand or Mass Spectrometry Lab of Monash Uni-
versity. Microanalysis was performed on a Carlo Erba Elemental
Analyzer EA 1108 at the Campbell Microanalytical Laboratory,
University of Otago, New Zealand. Anhydrous solvents were
obtained using a PureSolv MD Solvent Purification System. Ajax
Finechem Silica 200e325 mesh was used for column chromatog-
raphy and Merck silica gel 60H was used for flash chromatography.
4.1.1. 4,6-Dimethoxy-2,3-diphenyl-1H-indole-7-carbaldehyde
(16a). Indole 15a (1.99 g, 6.05 mmol) was added to a mixture of
phosphorus oxychloride (0.7 mL, 7.65 mmol) in N,N-DMF (20 mL).
The reaction was stirred at room temperature for 2.5 h before being
quenched with water (100 mL) and made basic with sodium hy-
droxide solution (1 M). The resulting precipitate was collected to
give the title compound 16a as a yellow solid (1.98 g, 92%). Mp
180e182 ꢀC. Lit.31 mp 183e184 ꢀC. 1H NMR (300 MHz, CDCl3):
d 3.81
(s, 3H, OCH3), 4.00 (s, 3H, OCH3), 6.15 (s, 1H, H5), 7.23e7.36 (m, 10H,
ArH), 10.41 (s, 1H, CHO), 10.59 (br s, 1H, NH).
3. Conclusion
4.1.2. 3-(4-Bromophenyl)-4,6-dimethoxy-1H-indole-7-carbaldehyde
(16b). This compound was prepared by the same method as
compound 16a, from indole 15b (1.01 g, 3.03 mmol), phosphorus
oxychloride (0.5 mL, 5.5 mmol) and N,N-DMF (10 mL). The title
compound 16b desired indole was obtained as a yellow solid (1.03 g,
94%) mp 207e209 ꢀC. Lit.31 mp 203e206 ꢀC. 1H NMR (300 MHz,
Ring closing metathesis strategies towards functionalised 1,7-
annulated 4,6-dimethoxyindoles have been presented. The activa-
tion of the C7 indole position provided convenient access to
cycloalkane and lactone fused indoles. Alternative pathways to
lactam fused indoles needs to be investigated in order to overcome
the similar reactivity of the indole and amide nitrogen atoms.
CDCl3): d 3.93 (s, 3H, OCH3), 3.99 (s, 3H, OCH3), 6.19 (s, 1H, H5), 7.08
(s, 1H, H2), 7.43 (d, J¼8.7 Hz, 2H, ArH), 7.48 (d, J¼8.7 Hz, 2H, ArH),
10.38 (s, 1H, CHO), 10.54 (br s, 1H, NH).
4. Experimental
4.1.3. 3-(4-Chlorophenyl)-4,6-dimethoxy-1H-indole-7-carbaldehyde
(16c). This compound was prepared by the same method as com-
pound 16a, from indole 15c (1.99 g, 6.95 mmol), phosphorus oxy-
chloride (0.7 mL, 7.6 mmol) and N,N-DMF (10 mL). The title
compound 16c was obtained as a yellow solid (1.84 g, 84%). Mp
4.1. General methods
Melting points were measured using a Mel-Temp melting point
apparatus and are uncorrected. Infrared spectra were recorded on

K. Wood et al. / Tetrahedron 67 (2011) 4093e4102
4097
218e220 ꢀC. Lit.33 mp 223e224 ꢀC. 1H NMR (300 MHz, CDCl3):
3.92 (s, 3H, OCH3), 3.99 (s, 3H, OCH3), 6.19 (s, 1H, H5), 7.07 (d,
bromide (0.85 mL, 9.82 mmol), potassium hydroxide (1.13 g,
2.00 mol) and DMSO (15 mL). The title compound 17d was obtained
as a white solid (1.52 g, 89%). Mp 124e126 ꢀC. 1H NMR (300 MHz,
d
J¼2.3 Hz, 1H, H2), 7.33 (d, J¼8.7 Hz, 2H, ArH), 7.49 (d, J¼8.7 Hz, 2H,
ArH), 10.38 (s, 1H, CHO), 10.53 (br s, 1H, NH).
CDCl3): d 2.32 (s, 3H, CH3), 3.81 (s, 3H, OCH3), 3.91 (s, 3H, OCH3),
4.77 (dd, J¼1.5, 17.2 Hz, 1H, H30), 4.97 (dd, J¼1.5, 10.3 Hz, 1H, H30),
5.04e5.07 (m, 2H, H10), 5.72e5.83 (m, 1H, H20), 6.17 (s, 1H, H5), 6.82
(s, 1H, H2), 7.09 (d, J¼8.0 Hz, 2H, ArH), 7.33 (d, J¼8.0 Hz, 2H, ArH),
4.1.4. 4,6-Dimethoxy-3-(4-methylphenyl)-1H-indole-7-carbaldehyde
(16d). This compound was prepared by the same method as
compound 16a, from indole 15d (1.95 g, 7.30 mmol), phosphorus
oxychloride (0.7 mL, 7.6 mmol) and N,N-DMF (10 mL). The title
compound 16d was obtained as a light tan solid (1.51 g, 67%). Mp
217e219 ꢀC. Found: C, 73.31; H, 5.91; N, 4.82%. C18H17NO3 requires:
10.37 (s, 1H, CHO). 13C NMR (75 MHz, CDCl3):
d 21.6, 53.7, 55.6, 57.4,
87.8, 107.3, 113.3, 116.6, 119.0, 128.7, 128.9, 129.9, 132.9, 134.8, 135.9,
136.3, 161.1, 164.8, 188.3. IR (KBr): nmax 2938, 2847, 1654, 1578, 1563,
1548, 1461, 1435, 1395, 1362, 1330, 1264, 1215, 1182, 1127, 1036, 918,
C, 73.20; H, 5.80; N, 4.74%. 1H NMR (300 MHz, CDCl3):
d
2.32 (s, 3H,
797, 784, 545 cmꢁ1
. UVevis (MeOH): lmax 339 nm (3
CH3), 3.86 (s, 3H, OCH3), 3.92 (s, 3H, OCH3), 6.11 (s, 1H, H5), 7.00 (d,
J¼2.3 Hz, 1H, H2), 7.11 (d, J¼7.9 Hz, 2H, ArH), 7.40 (d, J¼7.9 Hz, 2H,
ArH), 10.31 (s, 1H, CHO), 10.42 (br s, 1H, NH). 13C NMR (75 MHz,
8358 cmꢁ1 ꢁ1), 258 (23,797), 225 (18,249). HRMS (ESIþ): found
M
m/z 336.1593, [MþH]þ; C21H22NO3 required 336.1600.
CDCl3):
d
21.5, 55.8, 56.7, 87.1, 104.8, 110.6, 119.2, 121.9, 128.9, 129.7,
4.1.9. 1-Allyl-4,6-dimethoxy-2,3-diphenyl-7-(2-nitrovinyl)-1H-indole
(18a). A mixture of indole 17a (2.08 g, 5.24 mmol), nitromethane
(2.2 mL, 0.041 mol) and ammonium acetate (1.75 g, 0.023 mol)
were heated at reflux in isopropanol (70 mL) for 3 h. The precipitate
produced upon cooling was collected to give the title compound 18a
as a red solid (1.884 g, 82%). Mp 202e204 ꢀC. Found: C, 73.60; H,
5.50; N, 6.36%. C27H24N2O4 requires: C, 73.62; H, 5.49; N, 6.36%. 1H
132.8, 136.0, 138.1, 161.9, 163.4, 188.7. IR (KBr): nmax 3392, 2995,
2933, 2838,1627,1585,1547,1511,1451,1332,1258,1214,1143,1085,
1044, 965, 822, 807 cmꢁ1. UVevis (MeOH): lmax 294 nm (
3
9793 cmꢁ1 Mꢁ1), 262 (14,518), 226 (29,480). MS (ESIþ): m/z 318.07,
[MþNa]þ.
4.1.5. 1-Allyl-4,6-dimethoxy-2,3-diphenyl-1H-indole-7-carbaldehyde
(17a). Indole 16a (2.44 g, 6.83 mmol) and then allyl bromide
(2.3 mL, 0.027 mol) were added to a solution of potassium hy-
droxide (1.49 g, 0.027 mol) in DMSO (80 mL). The reaction was
stirred at room temperature for 1 h and then quenched with water
(100 mL). The resulting precipitate was collected to give the title
compound 17a as a light yellow solid (2.11 g, 78%). Mp 152e154 ꢀC.
NMR (300 MHz, CDCl3): d 3.79 (s, 3H, OCH3), 4.03 (s, 3H, OCH3),
4.75e4.76 (m, 2H, H10), 5.05 (dd, J¼17.1, 0.9 Hz, 1H, H30), 5.34 (dd,
J¼10.6, 0.9 Hz, 1H, H30), 5.97e6.09 (m, 1H, H20), 6.33 (s, 1H, H5),
7.16e7.29 (m, 10H, ArH), 8.02 (d, J¼12.8 Hz, 1H, H200), 8.77 (d,
J¼12.8 Hz, 1H, H100). 13C NMR (100 MHz, CDCl3):
d 49.6, 55.3, 56.3,
88.3, 98.0, 113.0, 116.4, 117.5, 125.7, 126.8, 128.1, 128.3, 131.3, 131.3,
131.4, 132.7, 134.0, 135.2, 136.2, 137.4, 138.9, 158.7, 160.2. IR (KBr):
nmax 2938, 1637, 1611, 1582, 1487, 1463, 1358, 1303, 1251, 1207, 1182,
1155, 1126, 1041, 970, 744, 698 cmꢁ1. UVevis (MeOH): lmax 283 nm
Lit.32 mp 156e157 ꢀC. 1H NMR (300 MHz, CDCl3):
d 3.72 (s, 3H,
OCH3), 3.92 (s, 3H, OCH3), 4.37 (dd, J¼17.1, 1.5 Hz, 1H, H30), 4.82 (dd,
J¼10.3, 1.5 Hz, 1H, H30), 4.97e4.98 (m, 2H, H10), 5.30e5.42 (m, 1H,
H20), 6.19 (s, 1H, H5), 7.06e7.20 (m, 10H, ArH), 10.42 (s, 1H, CHO).
(3
6992 cmꢁ1 Mꢁ1), 229 (15,637). MS (ESIþ): m/z 463.09, [MþNa]þ.
4.1.10. 1-Allyl-3-(4-bromophenyl)-4,6-dimethoxy-7-(2-nitrovinyl)-
1H-indole (18b). This compound was prepared by the same method
as compound 18a, from indole 17b (1.04 g, 2.59 mmol), nitro-
methane (1.1 mL, 0.021 mol), ammonium acetate (0.88 g, 0.011 mol)
and isopropanol (80 mL). The title compound 18b was obtained as
a red solid (0.750 g, 65%). Mp 144e146 ꢀC. 1H NMR (300 MHz,
4.1.6. 1-Allyl-3-(4-bromophenyl)-4,6-dimethoxy-1H-indole-7-car-
baldehyde (17b). This compound was prepared by the same
method as compound 17a, from indole 16b (1.03 g, 2.88 mmol), allyl
bromide (0.48 mL, 5.55 mmol), potassium hydroxide (0.63 g,
1.10 mmol) and DMSO (15 mL). The title compound 17b was
obtained as a light tan solid (1.04 g, 91%). Mp 188e190 ꢀC. 1H NMR
CDCl3):
d
3.81 (s, 3H, OCH3), 3.95 (s, 3H, OCH3), 4.85 (t, J¼2.1 Hz, 2H,
(300 MHz, CDCl3):
d
3.87 (s, 3H, OCH3), 3.98 (s, 3H, OCH3), 4.83 (dd,
H10), 5.03 (d, J¼17.2 Hz, 1H, H30), 5.26 (d, J¼10.5 Hz, 1H, H30),
6.01e6.10 (m, 1H, H20), 6.24 (s, 1H, H5), 6.81 (s, 1H, H2), 7.31 (d,
J¼8.5 Hz, 2H, H2000, H6000), 7.41 (d, J¼8.5 Hz, 2H, H3000, H5000), 7.93 (d,
J¼12.9 Hz, 1H, H200), 8.52 (d, J¼12.9 Hz, 1H, H100). 13C NMR (75 MHz,
J¼17.3, 1.5 Hz, 1H, H30), 5.05 (dd, J¼10.2, 1.5 Hz, 1H, H30), 5.12e5.14
(m, 2H, H10), 5.79e5.91 (m, 1H, H20), 6.25 (s, 1H, H5), 6.90 (s, 1H,
H2), 7.36 (d, J¼8.7 Hz, 2H, ArH), 7.46 (d, J¼8.7 Hz, 2H, ArH), 10.44 (s,
1H, CHO). 13C NMR (75 MHz, CDCl3):
d
53.8, 55.6, 57.4, 87.9, 107.4,
CDCl3): d 52.8, 55.7, 56.7, 88.5, 98.3, 112.3, 117.5, 118.4, 120.6, 128.8,
112.9,116.7,117.9,120.4,129.0,130.9,131.6,134.6,134.8,136.3,160.8,
131.0, 131.6, 132.3, 133.2, 134.5, 136.6, 137.8, 158.9, 160.6. IR (KBr):
164.9, 188.3. IR (KBr): nmax 2938, 2847, 1656, 1577, 1558, 1543, 1459,
nmax 2934, 1612, 1577, 1485, 1462, 1359, 1303, 1256, 1239, 1207, 1177,
1360, 1260, 1215, 1187, 1130, 1070, 1035, 1010, 794, 592 cmꢁ1
.
1138, 1071, 1049, 970 cmꢁ1. UVevis (MeOH): lmax 287 nm (
3
UVevis (MeOH): lmax 338 nm (
3
13,247 cmꢁ1
M
ꢁ1), 258 (29,019),
40,399 cmꢁ1 Mꢁ1), 225 (80,537). HRMS (ESIþ): found m/z 467.0384,
[MþNa]þ; C21H1981BrN2NaO4 required 467.0405.
228 (25,593). HRMS (ESIþ): found m/z 422.0345, [MþNa]þ;
C20H1879BrNNaO3 required 422.0368.
4.1.11. 1-Allyl-3-(4-chlorophenyl)-4,6-dimethoxy-7-(2-nitrovinyl)-
1H-indole (18c). This compound was prepared by the same method
as compound 18a, from indole 17c (1.72 g, 4.84 mmol), nitro-
methane (2.0 mL, 0.037 mol), ammonium acetate (1.45 g,
0.019 mol) and isopropanol (50 mL). The title compound 18c was
obtained as a red solid (1.53 g, 79%). Mp 146e148 ꢀC. Found: C,
63.08; H, 4.88; N, 6.72%. C21H19ClN2O4 requires: C, 63.24; H, 4.80; N,
4.1.7. 1-Allyl-3-(4-chlorophenyl)-4,6-dimethoxy-1H-indole-7-carbal-
dehyde (17c). This compound was prepared by the same method as
compound 17a, from indole 16c (1.95 g, 6.17 mmol), allyl bromide
(0.8 mL, 9.24 mmol), potassium hydroxide (1.21 g, 2.20 mol) and
DMSO (40 mL). The title compound 17c was obtained as a white
solid (1.24 g, 91%). Mp 188e190 ꢀC. Lit.32 mp 186e188 ꢀC. 1H NMR
(300 MHz, CDCl3):
d
3.80 (s, 3H, OCH3), 3.91 (s, 3H, OCH3),
7.02%. 1H NMR (300 MHz, CDCl3):
d 3.88 (s, 3H, OCH3), 4.02 (s, 3H,
4.79e4.86 (m, 1H, H30), 5.03e5.06 (m, 1H, H30), 5.11e5.14 (m, 2H,
H10), 5.78e5.91 (m,1H, H20), 6.17 (s,1H, H5), 6.83 (s,1H, H2), 7.24 (d,
J¼8.5 Hz, 2H, ArH), 7.35 (d, J¼8.5 Hz, 2H, ArH), 10.37 (s, 1H, CHO).
OCH3), 4.93 (t, J¼2.0 Hz, 2H, H10), 5.11 (d, J¼17.1 Hz, 1H, H30), 5.34
(d, J¼10.4 Hz, 1H, H30), 6.09e6.19 (m, 1H, H20), 6.32 (s, 1H, H5), 6.87
(s, 1H, H2), 7.32 (d, J¼8.4 Hz, 2H, H3000, H5000), 7.44 (d, J¼8.4 Hz, 2H,
H2000, H6000), 7.80 (d, J¼12.8 Hz, 1H, H200), 8.60 (d, J¼12.8 Hz, 1H, H100).
4.1.8. 1-Allyl-4,6-dimethoxy-3-(4-methylphenyl)-1H-indole-7-car-
baldehyde (17d). This compound was prepared by the same
method as compound 17a, from indole 16d (1.51 g, 4.89 mmol), allyl
13C NMR (75 MHz, CDCl3):
d 52.8, 55.7, 56.7, 88.5, 98.3, 112.6, 117.6,
118.3, 128.0, 128.8, 131.2, 132.3, 132.4, 133.2, 134.0, 136.6, 137.8,
158.9, 160.6. IR (KBr): nmax 2939, 2841, 1610, 1578, 1560, 1486, 1460,

4098
K. Wood et al. / Tetrahedron 67 (2011) 4093e4102
1303, 1257, 1239, 1206, 1177, 1136, 1091, 1050, 971 cmꢁ1. UVevis
THF (15 mL). The title compound 19c was obtained as a light brown
solid (0.27 g, 52%). Mp 70e72 ꢀC. 1H NMR (300 MHz, CDCl3):
2.56
(MeOH): lmax 281 nm (
3
15,382 cmꢁ1
M
ꢁ1), 232 (30,580). MS
d
(ESIþ): m/z 421.04, [MþNa]þ. 421.0931 (100.0%), 423.0902 (32.0%).
(dd, J¼7.4 Hz, 2H, H300), 3.71 (s, 3H, OCH3), 3.84 (s, 3H, OCH3), 4.15
(dt, J¼7.2 Hz, 1H, H200), 4.80e5.18 (m, 8H, H10, H30, H100, H500),
5.52e5.66 (m, 1H, H400), 6.00e6.12 (m, 1H, H20), 6.25 (s, 1H, H5),
6.74 (s, 1H, H2), 7.23 (d, J¼8.6 Hz, 2H, H3000, H5000), 7.38 (d, J¼8.6 Hz,
4.1.12. 1-Allyl-3-(4-methylphenyl)-4,6-dimethoxy-7-(2-nitrovinyl)-
1H-indole (18d). This compound was prepared by the same
method as compound 18a, from indole 17d (1.41 g, 4.04 mmol),
nitromethane (1.9 mL, 0.035 mol), ammonium acetate (1.39 g,
0.018 mol) and isopropanol (50 mL). The title compound 18d was
obtained as a red solid (1.46 g, 92%). Mp 147e149 ꢀC. Found: C,
70.09; H, 6.00; N, 7.52%. C22H22N2O4 requires: C, 69.83; H, 5.86; N,
2H, H2000, H6000). 13C NMR (75 MHz, CDCl3):
d 35.6, 37.1, 52.4, 55.4,
56.7, 79.1, 89.7, 104.2, 113.0, 116.4, 117.0, 117.8, 127.8, 129.4, 131.3,
131.9, 134.5, 134.8, 136.3, 136.8, 154.1, 156.2. IR (KBr): nmax 3078,
2937, 2840, 1610, 1585, 1548, 1488, 1463, 1376, 1336, 1270, 1204,
1127, 1089, 1047, 919, 835, 798 cmꢁ1. UVevis (MeOH): lmax 295 nm
7.40%. 1H NMR (300 MHz, CDCl3):
d
2.49 (s, 3H, CH3), 3.89 (s, 3H,
(3 M
12,579 cmꢁ1 ꢁ1), 226 (26,779). HRMS (ESIþ): found m/z
OCH3), 4.02 (s, 3H, OCH3), 4.82e4.85 (m, 2H, H10), 5.10 (dd, J¼16.9,
0.6 Hz, 1H, H30), 5.25 (dd, J¼10.5, 0.6 Hz, 1H, H30), 6.01e6.11 (m, 1H,
H20), 6.30 (s, 1H, H5), 6.86 (s, 1H, H2), 7.18 (d, J¼7.9 Hz, 2H, H3000,
H5000), 7.42 (d, J¼7.9 Hz, 2H, H2000, H6000), 8.01 (d, J¼12.9 Hz, 1H, H200),
441.1577, [MþH]þ; C24H2635ClN2O4 required 441.1581.
4.1.16. 1-Allyl-4,6-dimethoxy-3-(4-methylphenyl)-7-(1-nitropent-4-
en-2-yl)-1H-indole (19d). This compound was prepared by the
same method as compound 19a, from indole 18d (0.752 g,
1.99 mmol), allylmagnesium bromide (5.5 mL, 1 M) and anhydrous
THF (35 mL). The title compound 19d was obtained as a brown sticky
8.61 (d, J¼12.9 Hz, 1H, H100). 13C NMR (75 MHz, CDCl3):
d 21.6, 52.8,
55.7, 56.7, 88.3, 98.3, 112.8, 118.2, 118.7, 128.7, 128.8, 129.9, 132.5,
133.3, 136.2, 136.4, 137.8, 159.3, 160.6. IR (KBr): nmax 2936, 2839,
1608, 1578, 1460, 1357, 1298, 1257, 1239, 1208, 1177, 1044, 968,
residue (0.30 g, 36%). 1H NMR (300 MHz, CDCl3):
d 2.31 (s, 3H, CH3),
800 cmꢁ1. UVevis (MeOH): lmax 278 nm (
3
13,244 cmꢁ1 Mꢁ1), 232
2.54e2.59 (m, 2H, H300), 3.71 (s, 3H, OCH3), 3.84 (s, 3H, OCH3), 4.16
(dt, J¼7.2 Hz, 1H, H200), 4.75e5.17 (m, 8H, H10, H30, H100, H500),
5.52e5.66 (m, 1H, H400), 6.00e6.13 (m, 1H, H20), 6.24 (s, 1H, H5),
6.73 (s, 1H, H2), 7.08 (d, J¼7.8 Hz, 2H, ArH), 7.35 (d, J¼7.8 Hz, 2H,
(28,273). MS (ESIþ): m/z 401.07, [MþNa]þ.
4.1.13. 1-Allyl-4,6-dimethoxy-2,3-diphenyl-7-(1-nitropent-4-en-2-
yl)-1H-indole (19a). Allylmagnesium bromide (3 mL, 1 M) was
added to indole 18a (0.757 g, 1.72 mmol) in anhydrous THF (40 mL)
and the reaction stirred at room temperature under an argon at-
mosphere for 18 h. The reaction was quenched with ammonium
chloride solution (50 mL) and extracted with DCM (3ꢂ15 mL). The
combined organic layers were dried over anhydrous sodium sulfate
and reduced in vacuo to give the title compound 19a as a light tan
solid (0.697 g, 84%). Mp 172e174 ꢀC. 1H NMR (300 MHz, CDCl3):
ArH). 13C NMR (100 MHz, CDCl3):
d 35.3, 36.7, 51.9, 55.1, 56.3, 78.8,
89.3, 103.6, 112.9, 116.5, 117.1, 117.3, 128.2, 128.9, 129.5, 132.9, 134.3,
135.1,136.0,136.3,153.9,155.6. IR (KBr): nmax 2920,1607,1587, 1549,
1509, 1463, 1375, 1338, 1201, 1176, 1125, 1051, 823, 792 cmꢁ1
.
UVevis (MeOH): lmax 291 nm (3 M
15,194 cmꢁ1 ꢁ1), 233 (34,929).
HRMS (ESIþ): found m/z 421.2124, [MþH]þ; C25H29N2O4 required
421.2127.
d
2.67 (dd, J¼7.1 Hz, 2H, H300), 3.67 (s, 3H, OCH3), 3.91 (s, 3H, OCH3),
4.1.17. 1-Allyl-3-(4-bromophenyl)-4,6-dimethoxy-7-(1-nitrohex-5-
en-2-yl)-1H-indole (20b). Butenylmagnesium bromide (8 mL,
0.5 M) was added to indole 18b (0.767 g, 1.73 mmol) in anhydrous
THF (20 mL) and the reaction stirred at room temperature under an
argon atmosphere for 3 days. The reaction was quenched with
ammonium chloride solution (50 mL) and extracted with DCM
(3ꢂ15 mL). The combined organic layers were dried over anhydrous
sodium sulfate and reduced in vacuo to give the title compound 20b
as a light orange sticky residue (0.465 g, 54%). 1H NMR (300 MHz,
4.31e4.41 (m, 1H, H200), 4.75e5.28 (m, 8H, H10, H30, H100, H500),
5.64e5.78 (m, 1H, H400), 5.97e6.08 (m, 1H, H20), 6.33 (s, 1H, H5),
7.10e7.25 (m, 10H, ArH). 13C NMR (75 MHz, CDCl3):
d 35.0, 36.9,
48.6, 55.1, 56.2, 78.9, 89.6,103.8,113.4,115.4,116.1,117.1,125.1,126.5,
127.8,127.9,131.3,131.4,132.0,135.4,135.9,136.0,136.2,138.9,153.7,
155.8. IR (KBr): nmax 2936, 2838, 1598, 1586, 1548, 1502, 1442, 1408,
1379, 1360, 1320, 1256, 1208, 1176, 1122, 1069, 1039, 920, 733,
699 cmꢁ1. UVevis (MeOH): lmax 298 nm ( 12,464 cmꢁ1 Mꢁ1), 238
3
(29,264), 223 (37,840). HRMS (ESIþ): found m/z 483.2271, [MþH]þ;
CDCl3): d
1.86e2.08 (m, 4H, H300, H400), 3.77 (s, 3H, OCH3), 3.88 (s,
C30H31N2O4 required 483.2284.
3H, OCH3), 4.09e4.18 (m, 1H, H200), 4.74 (dd, J¼12.6, 5.6 Hz, 1H,
H100), 4.85e4.97 (m, 6H, H10, H30, H100, H60), 5.21 (dd, J¼10.5, 1.0 Hz,
1H, H30), 5.69e5.79 (m, 1H, H500), 6.04e6.15 (m, 1H, H20), 6.31 (s, 1H,
H5), 6.82 (s, 1H, H2), 7.38 (d, J¼8.6 Hz, 2H, H2000, C6000), 7.45 (d,
4.1.14. 1-Allyl-3-(4-bromophenyl)-4,6-dimethoxy-7-(1-nitropent-4-
en-2-yl)-1H-indole (19b). This compound was prepared by the
same method as compound 19a, from indole 18b (0.302 g,
0.68 mmol), allylmagnesium bromide (3 mL, 1 M) and anhydrous
THF (15 mL) The title compound 19b was obtained as a light brown
J¼8.6 Hz, 2H, H3000, H5000). 13C NMR (75 MHz, CDCl3):
d 31.3, 32.2,
35.8, 52.5, 55.4, 56.7, 79.7, 89.8, 104.1, 113.0, 115.3, 116.5, 117.0, 120.0,
129.4, 130.8, 131.6, 134.5, 135.3, 137.1, 138.5, 154.1, 156.3. IR (KBr):
nmax 3074, 2934, 2842, 1608, 1584, 1546, 1463, 1405, 1377, 1335,
1203, 1128, 1071, 1036, 1005, 920, 796 cmꢁ1. UVevis (MeOH): lmax
solid (0.33 g, 99%). Mp 74e76 ꢀC. 1H NMR (300 MHz, CDCl3):
d 2.64
(dd, J¼7.3 Hz, 2H, H300), 3.78 (s, 3H, OCH3), 3.92 (s, 3H, OCH3),
4.17e4.26 (m, 1H, H200), 4.84e5.25 (m, 8H, H10, H30, H100, H500),
5.59e5.72 (m,1H, H400), 6.07e6.19 (m,1H, H20), 6.33 (s,1H, H5), 6.82
(s, 1H, H2), 7.38 (d, J¼8.7 Hz, 2H, ArH), 7.45 (d, J¼8.7 Hz, 2H, ArH).
294 nm (3
13,689 cmꢁ1 Mꢁ1), 226 (28,083). HRMS (ESIþ): found m/z
499.1226, [MþH]þ; C25H2879BrN2O4 required 499.1232.
13C NMR (75 MHz, CDCl3):
d
35.2, 36.6, 51.9, 54.9, 56.2, 78.6, 89.3,
4.1.18. 1-Allyl-3-(4-chlorophenyl)-4,6-dimethoxy-7-(1-nitrohex-5-
en-2-yl)-1H-indole (20c). This compound was prepared by the
same method as compound 20b, from indole 18c (0.800 g,
2.00 mmol), butenylmagnesium bromide (6 mL, 0.5 M) and anhy-
drous THF (10 mL). Chromatography (SiO2, 50% DCM/hexane) gave
the title compound 20c as a light orange sticky residue (0.371 g,
103.6, 112.5, 115.9, 116.6, 117.3, 119.5, 128.9, 130.3, 131.2, 134.0, 134.8,
135.8, 136.3, 153.6, 155.7. IR (KBr): nmax 3075, 2936, 2839, 1609,
1585, 1548, 1463, 1403, 1375, 1336, 1204, 1127, 1070, 1047, 1008, 918,
832, 797 cmꢁ1. UVevis (MeOH): lmax 295 nm ( 13,104 cmꢁ1 Mꢁ1),
3
226 (28,097). HRMS (ESIþ): found m/z 507.0892, [M]þ;
C24H2579BrN2NaO4 required 507.0895.
45%). 1H NMR (300 MHz, CDCl3): 1.86e2.12 (m, 4H, H300, H400), 3.77
d
(s, 3H, OCH3), 3.88 (s, 3H, OCH3), 4.09e4.18 (m, 1H, H200), 4.70 (dd,
J¼12.5, 5.6 Hz, 1H, H100), 4.85e4.98 (m, 6H, H10, H30, H100, H60), 5.21
(dd, J¼10.5, 1.0 Hz, 1H, H30), 5.66e5.79 (m, 1H, H500), 6.04e6.16 (m,
1H, H20), 6.31 (s, 1H, H5), 6.82 (s, 1H, H2), 7.29 (d, J¼8.6 Hz, 2H, H3000,
H5000), 7.43 (d, J¼8.6 Hz, 2H, H2000, C6000). 13C NMR (75 MHz, CDCl3):
4.1.15. 1-Allyl-3-(4-chlorophenyl)-4,6-dimethoxy-7-(1-nitropent-4-
en-2-yl)-1H-indole (19c). This compound was prepared by the
same method as compound 19a, from indole 18c (0.466 g,
1.17 mmol), allylmagnesium bromide (3.5 mL, 1 M) and anhydrous

K. Wood et al. / Tetrahedron 67 (2011) 4093e4102
4099
d
31.3, 32.2, 35.8, 52.5, 55.4, 56.7, 79.8, 89.8, 104.1, 113.1, 115.3, 116.4,
(
3
12,003 cmꢁ1
M
ꢁ1), 228 (22,317). HRMS (ESIþ): found m/z
117.0, 127.9, 129.5, 131.3, 131.9, 134.5, 134.8, 137.1, 138.5, 154.1, 156.3.
IR (KBr): nmax 3083, 2933, 2838, 1585, 1547, 1488, 1463, 1405, 1377,
1335, 1204, 1128, 1045, 916, 836, 796 cmꢁ1. UVevis (MeOH): lmax
413.1260, [MþH]þ; C22H2235ClN2O4 required 413.1268.
4.1.22. 10,11-Dihydro-1,3-dimethoxy-4-(4-methylphenyl)-11-(nitro
methyl)-7H-azocino[3,2,1-hi]indole (21d). This compound was pre-
pared by the same method as compound 21b, from indole 19d
(0.200 g, 4.76 mmol), Grubbs’ catalyst (second gen, 5e10 mol %) and
degassed toluene (40 mL). Chromatography (SiO2, 50% DCM/hex-
ane) gave the title compound 21d as a white solid (0.114 g, 61%). Mp
294 nm (3
13,528 cmꢁ1 Mꢁ1), 227 (27,715). HRMS (ESIþ): found m/z
455.1729, [MþH]þ; C25H2835ClN2O4 required 455.1738.
4.1.19. 1-Allyl-3-(4-methylphenyl)-4,6-dimethoxy-7-(1-nitrohex-5-en-
2-yl)-1H-indole (20d). This compound was prepared by the same
method as compound 20b, from indole 18d (0.701 g, 1.85 mmol),
butenylmagnesium bromide (11 mL, 0.5 M) and anhydrous THF
(10 mL). Chromatography (SiO2, 50% DCM/hexane) gave the title
compound 20d as a light orange sticky residue (0.136 g, 17%). 1H NMR
175e177 ꢀC. 1H NMR (300 MHz, CDCl3):
d 2.31 (s, 3H, CH3),
2.49e2.61 (m, 1H, H10), 2.76e2.83 (m, 1H, H10), 3.70 (s, 3H, OCH3),
3.79 (s, 3H, OCH3), 4.25 (dd, J¼14.9, 8.2 Hz,1H, H7), 4.76 (dd, J¼12.9,
3.0 Hz, 1H, CH2NO2), 4.94e5.00 (m, 1H, H11), 5.06 (dd, J¼12.9,
9.4 Hz, 1H, CH2NO2), 5.39 (dd, J¼14.4, 7.7 Hz, 1H, H7), 5.63e5.70 (m,
2H, H8, H9), 6.20 (s, 1H, H2), 6.75 (s, 1H, H5), 7.08 (d, J¼8.7 Hz, 2H,
H30, H50), 7.36 (d, J¼8.7 Hz, 2H, H20, H60). 13C NMR (75 MHz, CDCl3):
(300 MHz, CDCl3): d
1.85e2.16 (m, 4H, H300, H400), 3.77 (s, 3H, OCH3),
3.88 (s, 3H, OCH3), 4.15e4.19 (m, 1H, H200), 4.71 (dd, J¼12.5, 5.3 Hz,
1H, H100), 4.86e4.98 (m, 6H, H10, H30, H100, H60), 5.18 (dd, J¼10.5,
1.0 Hz, 1H, H30), 5.72e5.79 (m, 1H, H500), 6.04e6.15 (m, 1H, H20), 6.30
(s, 1H, H5), 6.80 (s, 1H, H2), 7.14 (d, J¼7.9 Hz, 2H, H3000, H5000), 7.41 (d,
d
21.6, 35.7, 36.2, 47.6, 55.6, 56.8, 81.3, 89.8, 104.9, 113.4, 117.6, 123.9,
128.6, 129.1, 129.8, 133.2, 133.5, 135.6, 138.2, 154.5, 154.6. IR (KBr):
J¼7.9 Hz, 2H, H2000, C6000). 13C NMR (75 MHz, CDCl3):
d 21.1, 30.9, 31.7,
nmax 2920, 1607, 1587, 1549, 1509, 1463, 1375, 1338, 1201, 1176, 1125,
1051, 823, 792 cmꢁ1.
. UVevis (MeOH): lmax 292 nm (3
35.4, 51.9, 55.0, 56.2, 79.4, 89.2, 103.5, 112.9, 114.7, 116.4, 117.0, 128.1,
128.9, 129.4, 132.8, 134.2, 135.1, 136.5, 138.1, 153.7, 155.6. IR (KBr):
nmax 3078, 2932, 2838, 1603, 1585,1548, 1463,1377, 1334, 1203,1125,
11,037 cmꢁ1 Mꢁ1), 233 (23,873). HRMS (ESIþ): found m/z 393.1817,
[MþH]þ; C23H25N2O4 required 393.1814.
1068, 1041, 994, 913, 797, 733 cmꢁ1. UVevis (MeOH): lmax 289 nm (
3
19,816 cmꢁ1 Mꢁ1), 233 (46,678). HRMS (ESIþ): found m/z 435.2280,
4.1.23. 4-(4-Bromophenyl)-1,3-dimethoxy-12-(nitromethyl)-7,10,11,12-
tetrahydro-7H-azonino[3,2,1-hi]indole (22b). This compound was
prepared by the same method as compound 21b, from indole 20b
(0.313 g, 0.63 mmol), Grubbs’ catalyst (second gen, 5e10 mol %) and
degassed toluene (40 mL). Chromatography (SiO2, 50% DCM/hexane)
gave the title compound 22b as a light tan solid (0.120 g, 40%). Mp
[MþH]þ; C26H31N2O4 required 435.2284.
4.1.20. 4-(4-Bromophenyl)-10,11-dihydro-1,3-dimethoxy-11-(nitro
methyl)-7H-azocino[3,2,1-hi]indole (21b). Indole 19b (0.220 g,
0.45 mmol) and Grubbs’ catalyst (second gen, 5e10 mol %) were
heated at reflux under an argon atmosphere in dry, degassed tol-
uene (30 mL) for 4.5 h. The reaction mixture was then cooled and
reduced in vacuo. Chromatography (SiO2, 50% DCM/hexane) gave
the title compound 21b as an off white solid (0.083 g, 40%). Mp
150e152 ꢀC. 1H NMR (300 MHz, CDCl3):
d 1.80e2.33 (m, 4H, H10,
H11), 3.82 (s, 3H, OCH3), 3.93 (s, 3H, OCH3), 4.32e4.41 (m, 1H, H12),
4.62 (dd, J¼19.3, 8.0 Hz, 1H, H7), 4.79 (dd, J¼13.2, 4.9 Hz, 1H,
CH2NO2), 5.11 (dd, J¼13.2, 8.9 Hz, 1H, CH2NO2), 5.29e5.38 (m, 2H, H7,
H8), 5.75e5.88 (m, 1H, H9), 6.36 (s, 1H, H2), 6.90 (s, 1H, H5), 7.43 (d,
J¼7.8 Hz, 2H, ArH), 7.49 (d, J¼7.8 Hz, 2H, ArH). 13C NMR (75 MHz,
164e166 ꢀC. 1H NMR (300 MHz, CDCl3):
d 2.50e2.61 (m, 1H, H10),
2.75e2.82 (m, 1H, H10), 3.71 (s, 3H, OCH3), 3.80 (s, 3H, OCH3), 4.26
(dd, J¼15.1, 8.3 Hz, 1H, H7), 4.78 (dd, J¼12.8, 3.0 Hz, 1H, CH2NO2),
4.92e4.99 (m, 1H, H11), 5.01e5.09 (m, 1H, CH2NO2), 5.40 (dd,
J¼14.4, 7.7 Hz, 1H, H7), 5.63e5.71 (m, 2H, H8, H9), 6.20 (s, 1H, H2),
6.77 (s,1H, H5), 7.32 (d, J¼8.7 Hz, 2H, H20, H60), 7.38 (d, J¼8.7 Hz, 2H,
CDCl3): d 25.7, 33.4, 35.7, 49.8, 55.2, 56.0, 80.4, 89.6,105.5,112.9,116.7,
119.6, 124.9, 130.4, 130.4, 131.0, 131.6, 134.6, 138.5, 153.6, 155.0. IR
(KBr): nmax 2939, 2837, 1608, 1586, 1547, 1459, 1377, 1203, 1174, 1124,
1070, 1051, 1007, 833, 797 cmꢁ1. UVevis (MeOH): lmax 299 nm (
3
12,254 cmꢁ1
M
ꢁ1), 232 (21,210). HRMS (ESIþ): found m/z 471.0908,
H30, H50). 13C NMR (75 MHz, CDCl3):
d 34.2, 34.7, 46.1, 54.1, 55.4,
[MþH]þ; C23H2479BrN2O4 required 471.0919.
79.7, 88.5, 103.5, 111.6, 115.0, 118.6, 122.4, 127.8, 129.5, 130.0, 132.2,
133.7, 136.9, 152.9, 153.4. IR (KBr): nmax 2929, 2834, 1613, 1587, 1547,
4.1.24. 4-(4-Chlorophenyl)-1,3-dimethoxy-11-(nitromethyl)-
7,10,11,12-tetrahydro-7H-azonino[3,2,1-hi]indole (22c). This com-
pound was prepared by the same method as compound 21b, from
indole 20c (0.263 g, 0.58 mmol), Grubbs’ catalyst (second gen,
5e10 mol %) and degassed toluene (40 mL). Chromatography (SiO2,
50% DCM/hexane) gave the title compound 22c as an off white solid
(0.10 g, 42%). Mp 166e168 ꢀC. 1H NMR (300 MHz, CDCl3):
1510, 1463, 1375, 1337, 1201, 1178, 1125, 1070, 1051, 1007, 795 cmꢁ1
.
UVevis (MeOH): lmax 298 nm (3 M
13,220 cmꢁ1 ꢁ1), 227 (24,154).
HRMS (ESIþ): found m/z 479.0581, [MþNa]þ; C22H2179BrN2O4Na
required 479.0582.
4.1.21. 4-(4-Chlorophenyl)-10,11-dihydro-1,3-dimethoxy-11-(nitro
methyl)-7H-azocino[3,2,1-hi]indole (21c). This compound was pre-
pared by the same method as compound 21b, from indole 19c
(0.220 g, 0.50 mmol), Grubbs’ catalyst (second gen, 5e10 mol %) and
degassed toluene (40 mL). Chromatography (SiO2, 50% DCM/hex-
ane) gave the title compound 21c as a white solid (0.10 g, 49%). Mp
168e170 ꢀC. Found: C, 64.01; H, 5.25; N, 6.85%. C22H21ClN2O4 re-
quires: C, 64.00; H, 5.13; N, 6.79%. 1H NMR (300 MHz, CDCl3):
d
1.70e2.19 (m, 4H, H11, H10), 3.70 (s, 3H, OCH3), 3.82 (s, 3H, OCH3),
4.20e4.28 (m, 1H, H12), 4.50 (dd, J¼18.9, 7.7 Hz, 1H, H7), 4.68 (dd,
J¼13.2, 4.9 Hz, 1H, CH2NO2), 5.00 (dd, J¼13.2, 8.9 Hz, 1H, CH2NO2),
5.18e5.27 (m, 2H, H7, H8), 5.72 (dd, J¼18.9, 9.5 Hz, 1H, H9), 6.25 (s,
1H, H2), 6.78 (s, 1H, H5), 7.23 (d, J¼8.5 Hz, 2H, ArH), 7.38 (d,
J¼8.5 Hz, 2H, ArH). 13C NMR (75 MHz, CDCl3):
d 26.1, 33.9, 36.4, 50.3,
55.5, 56.5, 80.8, 90.2, 105.9, 113.4, 117.2, 125.2, 127.9, 130.9, 131.1,
131.9, 132.3, 134.6, 139.0, 154.1, 155.5. IR (KBr): nmax 2939, 2834,
1615, 1588, 1548, 1463, 1378, 1337, 1203, 1171, 1124, 1089, 1053, 797,
d
2.55e2.67 (m, 1H, H10), 2.77e2.88 (m, 1H, H10), 3.76 (s, 3H,
OCH3), 3.85 (s, 3H, OCH3), 4.30 (dd, J¼12.3, 8.2 Hz, 1H, H7), 4.83 (dd,
J¼15.2, 3.0 Hz, 1H, CH2NO2), 4.99e5.19 (m, 2H, H11, CH2NO2), 5.44
(dd, J¼15.0, 9.0 Hz, 1H, H7), 5.66e5.76 (m, 2H, H8, H9), 6.26 (s, 1H,
H2), 6.81 (s, 1H, H5), 7.29 (d, J¼8.7 Hz, 2H, ArCH), 7.45 (d, J¼8.7 Hz,
617 cmꢁ1. UVevis (MeOH): lmax 297 nm ( 12,457 cmꢁ1 Mꢁ1), 236
3
(22,275). HRMS (ESIþ): found m/z 427.1425, [MþH]þ;
C23H2435ClN2O4 required 427.1425.
2H, ArCH). 13C NMR (75 MHz, CDCl3):
d 34.3, 35.2, 47.1, 55.1, 56.3,
80.6, 89.4, 104.5, 112.6, 115.9, 123.3, 127.5, 128.7, 130.6, 131.4, 133.1,
134.1, 137.8, 153.8, 154.3. IR (KBr): nmax 2936, 2834, 1610, 1587, 1548,
1508, 1488, 1463, 1410, 1378, 1338, 1280, 1201, 1179, 1125, 1089,
4.1.25. 1,3-Dimethoxy-4-(4-methylphenyl)-12-(nitromethyl)-7,10,11,
12-tetrahydro-7H-azonino[3,2,1-hi]indole (22d). This compound
was prepared by the same method as compound 21b, from indole
20d (0.132 g, 3.04 mmol), Grubbs’ catalyst (second gen, 5e10 mol %)
1050, 1012, 835, 796 cmꢁ1
. UVevis (MeOH): lmax 297 nm

4100
K. Wood et al. / Tetrahedron 67 (2011) 4093e4102
and degassed toluene (40 mL). Chromatography (SiO2, 50% DCM/
4.1.29. Allyl 1-allyl-4,6-dimethoxy-2,3-diphenyl-1H-indole-7-carbox-
ylate (24a). This compound was prepared by the same method as
compound 17a, from indole 28a (0.960 g, 2.32 mmol), allyl bromide
(1.2 mL, 13.9 mmol), potassium hydroxide (0.542 g, 1.31 mmol) and
DMSO (20 mL). The title compound 24a was obtained as a white solid
hexane) gave the title compound 22d as a light tan solid (0.07 g,
54%). Mp 138e140 ꢀC. 1H NMR (300 MHz, CDCl3):
d 1.72e1.85 (m,
1H, H11),1.93e2.05 (m, 1H, H11), 2.08e2.17 (m, 1H, H10), 2.21e2.32
(m,1H, H10), 2.39 (s, 3H, CH3), 3.78 (s, 3H, OCH3), 3.89 (s, 3H, OCH3),
4.27e4.35 (m, 1H, H12), 4.57 (dd, J¼19.6, 8.5 Hz, 1H, H7), 4.73 (dd,
J¼13.2, 4.7 Hz, 1H, CH2NO2), 5.09 (dd, J¼13.2, 9.0 Hz, 1H, CH2NO2),
5.25e5.34 (m, 2H, H7, H8), 5.79 (dd, J¼17.9, 9.0 Hz, 1H, H9), 6.32 (s,
1H, H2), 6.85 (s, 1H, H5), 7.16 (d, J¼7.8 Hz, 2H, H30, H50), 7.44 (d,
(0.853 g, 81%). Mp 119e121 ꢀC. 1H NMR (300 MHz, CDCl3):
d 3.73 (s,
3H, OCH3), 3.91 (s, 3H, OCH3), 4.60 (dt, J¼4.4, 1.8 Hz, 2H, H10), 4.68
(dd, J¼17.2, 1.2 Hz, 1H,0H30), 4.83 (dt, J¼5.7, 1.2 Hz, 2H, H300), 5.01 (dd,
J¼10.5, 1.2 Hz, 1H, H3 ), 5.28 (dd, J¼10.3, 1.2 Hz, 1H, H500), 5.54 (dd,
J¼17.2, 1.5 Hz, 1H, H500), 5.67e5.79 (m, 1H, H20), 5.98e6.11 (m, 1H,
H400), 6.32 (s, 1H, H5), 7.12e7.27 (m, 10H, ArH). 13C NMR (75 MHz,
J¼7.8 Hz, 2H, H20, H60). 13C NMR (75 MHz, CDCl3):
d 21.1, 25.7, 33.5,
35.9, 49.7, 55.1, 56.1, 80.4, 89.6,105.5,113.3,117.9,124.8,128.2,129.3,
130.3, 131.7, 132.6, 135.2, 138.5, 153.7, 154.8. IR (KBr): nmax 3012,
2920, 2842, 1587, 1548, 1462, 1377, 1338, 1202, 1173, 1124, 1052,
CDCl3):
d 47.1, 55.2, 57.6, 66.0, 89.1, 101.2, 112.9, 115.8, 115.9, 118.5,
125.3, 126.6, 127.7, 127.8, 131.3, 131.7, 131.9, 133.8, 133.9, 135.5, 137.9,
155.1, 155.8, 167.7. IR (KBr): nmax 3057, 2992, 2936, 2839, 1719, 1587,
1551, 1501, 1448, 1410, 1352, 1261, 1209, 1167, 1130, 1097, 1038, 923,
796 cmꢁ1. UVevis (MeOH): lmax 292 nm ( 12,239 cmꢁ1 Mꢁ1), 237
3
(26,104). HRMS (ESIþ): found m/z 407.1963, [MþH]þ; C24H27N2O4
required 407.1971.
764, 697 cmꢁ1. UVevis (MeOH): lmax 300 nm ( 10,317 cmꢁ1 ꢁ1),
3 M
240 (25,521). HRMS (ESIþ): found m/z 454.2014, [MþH]þ; C29H28NO4
required 454.2018.
4.1.26. 10,12-Dimethoxy-8,9-diphenyl-3H-[1,5]oxazonino[3,4,5-hi]
indol-1-(6H)-one (23a). This compound was prepared by the same
method as compound 21b, from indole 24a (0.217 g, 4.78 mmol),
Grubbs’ catalyst (second gen, 5e10 mol %) and degassed toluene
(20 mL). Chromatography (SiO2, 50% DCM/hexane) gave the title
compound 23a as a white solid (0.077 g, 38%). Mp 189e191 ꢀC. 1H
4.1.30. Allyl 1-allyl-3-(4-bromophenyl)-4,6-dimethoxy-1H-indole-7-
carboxylate (24b). This compound was prepared by the same
method as compound 17a, from indole 28b (0.583 g, 1.40 mmol),
allyl bromide (0.36 mL, 4.16 mmol), potassium hydroxide (0.24 g,
4.28 mmol) and DMSO (20 mL). The title compound 24b was
obtained as a white solid (0.587 g, 92%). Mp 122e124 ꢀC. Found: C,
60.55; H, 4.80; N, 3.00%. C23H22BrNO4 requires: C, 60.54; H, 4.86; N,
NMR (300 MHz, CDCl3): d 3.74 (s, 3H, OCH3), 3.96 (s, 3H, OCH3), 5.12
(m,1H, CH2), 5.62 (dt, J¼10.7, 1.8 Hz,1H, CH), 6.03 (dt, J¼10.7, 4.2 Hz,
1H, CH), 6.29 (s, 1H, H11), 7.12e7.30 (m, 10H, ArH). 13C NMR
3.07%. 1H NMR (300 MHz, CDCl3):
d 3.81 (s, 3H, OCH3), 3.89 (s, 3H,
(75 MHz, CDCl3): d 45.1, 55.7, 57.7, 61.9, 89.1, 99.4, 113.1, 116.2, 125.9,
OCH3), 4.63 (dt, J¼5.4, 1.6 Hz, 2H, H10), 4.83 (dt, J¼5.7, 1.4 Hz, 2H,
H300), 5.03 (dd, J¼17.1, 1.2 Hz, 1H, H30), 6.17 (dd, J¼10.3, 1.2 Hz, 1H,
H30), 5.29 (dd, J¼10.4, 1.5 Hz, 1H, H500), 5.44 (dd, J¼17.2, 1.5 Hz, 1H,
H500), 5.86e6.10 (m, 2H, H20, H400), 6.31 (s, 1H, H5), 6.88 (s, 1H, H2),
7.38 (d, J¼8.7 Hz, 2H, ArH), 7.45 (d, J¼8.7 Hz, 2H, ArH). 13C NMR
127.1, 127.2, 128.4, 128.6, 129.7, 131.6, 131.8, 132.2, 132.6, 132.7, 135.6,
139.8, 156.9,157.9, 168.3. IR (KBr): nmax 2936, 2844,1723,1584,1457,
1346, 1254, 1201, 1163, 1131, 1099, 1042, 805, 760, 697 cmꢁ1. UVevis
(MeOH): lmax 312 nm (3 M
16,168 cmꢁ1 ꢁ1), 249 (34,719). HRMS
(ESIþ): found m/z 426.1705, [MþH]þ; C27H24NO4 required 426.1705.
(75 MHz, CDCl3):
d 50.3, 55.2, 57.6, 66.1, 88.7, 100.7, 112.0, 116.8,
117.6, 118.8, 119.7, 126.7, 130.5, 131.2, 131.9, 133.4, 134.4, 134.6, 155.5,
155.9, 167.5. IR (KBr): nmax 2930, 2841, 1719, 1701, 1604, 1586, 1560,
1460, 1357, 1262, 1242, 1206, 1168, 1141, 1103, 1068, 1021, 923,
4.1.27. 9-(4-Bromophenyl)-10,12-dimethoxy-3H-[1,5]oxazonino
[3,4,5-hi]indol-1-(6H)-one (23b). This compound was prepared by
the same method as compound 21b, from indole 24b (0.487 g,
1.07 mmol), Grubbs’ catalyst (second gen, 5e10 mol %) and
degassed toluene (15 mL). Chromatography (SiO2, 50% DCM/hex-
ane) gave the title compound 23b as an off white solid (0.355g, 78%).
3
791 cmꢁ1. UVevis (MeOH): lmax 294 nm ( 17,226 cmꢁ1Mꢁ), 239
(33,198). MS (ESIþ): m/z 480.02, [MþNa]þ.
4.1.31. Allyl 1-allyl-3-(4-chlorophenyl)-4,6-dimethoxy-1H-indole-7-
carboxylate (24c). This compound was prepared by the same
method as compound 17a, from indole 28c (0.516 g, 1.39 mmol),
allyl bromide (0.4 mL, 4.62 mmol), potassium hydroxide (0.202 g,
3.60 mmol) and DMSO (15 mL). The title compound 24c was
obtained as a light tan solid (0.355 g, 62%). Mp 116e118 ꢀC. 1H NMR
Mp 294e296 ꢀC. 1H NMR (300 MHz, CDCl3):
d 3.82 (s, 3H, OCH3),
3.85 (s, 3H, OCH3), 4.61e4.75 (m, 4H, H3, H6), 5.48 (dt, J¼15.5,
5.3 Hz, 1H, CH), 5.89 (dt, J¼15.7, 4.3 Hz, 1H, CH), 6.27 (s, 1H, H5),
6.83 (s, 1H, H2), 7.38 (d, J¼8.7 Hz, 2H, ArH), 7.46 (d, J¼8.7 Hz, 2H,
ArH). IR (KBr): nmax 2955, 2929, 2841, 1717, 1609, 1584, 1558, 1543,
1460, 1356, 1261, 1207, 1169, 1140, 1099, 1068, 1007, 795 cmꢁ1
.
(300 MHz, CDCl3): d 3.63 (s, 3H, OCH3), 3.71 (s, 3H, OCH3), 4.50 (dt,
UVevis (MeOH): lmax 286 nm (3 M
6455 cmꢁ1 ꢁ1), 239 (12,420).
J¼5.3, 1.6 Hz, 2H, H10), 4.69 (dt, J¼5.6, 1.5 Hz, 2H, H300), 4.89 (dd,
J¼17.2, 1.4 Hz, 1H, H30), 5.03 (dd, J¼10.4, 1.4 Hz, 1H, H30), 5.16 (dd,
J¼10.4, 1.5 Hz, 1H, H500), 5.31 (dd, J¼17.2, 1.5 Hz, 1H, H500), 5.73e5.96
(m, 2H, H20, H400), 6.21 (s, 1H, H5), 6.76 (s, 1H, H2), 7.16 (d, J¼8.6 Hz,
2H, ArH), 7.31 (d, J¼8.6 Hz, 2H, ArH). 13C NMR (75 MHz, CDCl3):
HRMS (ESIþ): found m/z 428.0492, [MþH]þ; C21H1979BrNO4 re-
quired 428.0497.
4.1.28. 9-(4-Chlorophenyl)-10,12-dimethoxy-3H-[1,5]oxazonino
[3,4,5-hi]indol-1-(6H)-one (23c). This compound was prepared by
the same method as compound 21b, from indole 24c (0.255 g,
6.18 mmol), Grubbs’ catalyst (second gen, 5e10 mol %) and
degassed toluene (10 mL). Chromatography (SiO2, 50% DCM/hex-
ane) gave the title compound 23c as an off white solid (0.035g, 15%).
d
50.2, 55.1, 57.5, 66.0, 88.6, 100.7, 112.0, 116.7, 117.5, 118.7, 126.7,
127.5, 130.7, 131.5, 131.9, 133.3, 134.1, 134.2, 155.4, 155.8, 167.4. IR
(KBr): nmax 3086, 2935, 2841, 1701, 1609, 1590, 1547, 1462, 1452,
1413, 1357, 1264, 1244, 1218, 1184, 1173, 1144, 1102, 1015, 920, 835,
791 cmꢁ1. UVevis (MeOH): lmax 294 nm ( 14,673 cmꢁ1 Mꢁ1), 239
3
Mp 288e290 ꢀC. 1H NMR (300 MHz, CDCl3):
d
3.79 (s, 3H, OCH3),
(28,778). HRMS (ESIþ): found m/z 412.1312, [MþH]þ;
3.84 (s, 3H, OCH3), 4.62e4.73 (m, 4H, H3, H6), 5.49 (dt, J¼15.7,
5.1 Hz, H4), 5.89 (dt, J¼15.3, 4.3 Hz, 1H, H5), 6.28 (s, 1H, H11), 6.83
(s, 1H, H8), 7.30 (d, J¼8.3 Hz, 2H, ArH), 7.44 (d, J¼8.3 Hz, 2H, ArH).
C23H2335ClNO4 required 412.1316.
4.1.32. 4,6-Dimethoxy-2,3-diphenyl-7-trichloroacetylindole
(27a). Indole 15a (1.08 g, 3.28 mmol) and trichloroacetyl chloride
(1.8 mL, 0.016 mol) were heated at reflux in 1,2-dichloroethane
(25 mL) for 3 h. The reaction was quenched with water (80 mL) and
extracted with DCM (3ꢂ15 mL). The combined organic layers were
dried over anhydrous sodium sulfate and reduced in vacuo to give
the title compound 27a as a yellow solid (1.00 g, 65%). Mp
13C NMR (75 MHz, CDCl3):
d 48.6, 55.1, 57.4, 65.3, 88.4, 100.4, 111.7,
117.0, 124.5,126.9, 127.5, 129.8, 130.7,131.6, 133.9, 139.7, 155.0, 155.7,
167.7. IR (KBr): nmax 2933, 2841, 1719, 1607, 1586, 1563, 1451, 1354,
1262, 1209, 1171, 1141, 1091, 1047, 1012, 962, 832, 800 cmꢁ1. UVevis
(MeOH): lmax 292 nm (3
4112 cmꢁ1 Mꢁ1), 239 (6826). HRMS (ESIþ):
found m/z 384.1006, [MþH]þ; C21H1935ClNO4 required 384.1003.

K. Wood et al. / Tetrahedron 67 (2011) 4093e4102
4101
176e177 ꢀC. 1H NMR (300 MHz, CDCl3):
3H, OCH3), 6.19 (s, 1H, H5), 7.22e7.39 (m, 10H, ArH), 10.44 (br s, 1H,
NH). 13C NMR (75 MHz, CDCl3):
55.4, 55.5, 87.7, 98.2, 98.6, 113.4,
d
3.82 (s, 3H, OCH3), 3.99 (s,
4.1.37. Allyl 3-(4-chlorophenyl)-4,6-dimethoxy-1H-indole-7-carbox-
ylate (28c). This compound was prepared by the same method as
compound 28a, from indole 27c (0.853 g, 1.97 mmol), allyl alcohol
(0.27 mL, 3.97 mmol), potassium hydroxide (0.222 g, 3.97 mmol)
and THF (15 mL). The title compound 28c was obtained as an off
white solid (0.613 g, 84%). Mp 145e147 ꢀC. 1H NMR (300 MHz,
d
115.2,126.3, 127.3, 127.4,127.8,128.4,131.2,131.9, 132.9, 135.2,138.9,
160.2, 161.7, 182.0. IR (KBr): nmax 3052, 2940, 2846, 1632, 1586,1543,
1463, 1374, 1361, 1239, 1223, 1138, 991, 796, 693 cmꢁ1. UVevis
(MeOH): lmax 310 nm (
3
18,731 cmꢁ1
M
ꢁ1), 270 (22,184), 248
CDCl3): d 3.89 (s, 3H, OCH3), 3.99 (s, 3H, OCH3), 4.89e4.91 (m, 2H,
(26,767), 230 (30,919). HRMS (ESIþ): found m/z 474.0432, [MþH]þ;
H30), 5.30 (dd, J¼10.5, 1.4 Hz, 1H, H50), 5.50 (dd, J¼17.2, 1.5 Hz, 1H,
H50), 6.03e6.16 (m, 1H, H40), 6.28 (s, 1H, H5), 7.09 (d, J¼2.3 Hz, 1H,
H2), 7.32 (d, J¼8.5 Hz, 2H, ArH), 7.50 (d, J¼8.5 Hz, 2H, ArH), 10.3 (br
C24H1935Cl3NO3 required 474.0431.
4.1.33. 3-(4-Bromophenyl)-4,6-dimethoxy-7-trichloroacetylindole
(27b). This compound was prepared by the same method as
compound 27a, from indole 15b (3.00 g, 9.04 mmol), tri-
chloroacetyl chloride (5.0 mL, 44.8 mmol) and 1,2-dichloroethane
(25 mL). Chromatography (SiO2, 30% DCM/hexane) gave the title
compound 27b as a yellow solid (0.613 g, 14%). Mp 187e189 ꢀC. Lit.33
mp 190e192 ꢀC. 1H NMR (300 MHz, CDCl3): 3.93 (s, 3H, OCH3), 3.99
(s, 3H, OCH3), 6.23 (s, 1H, H5), 7.08 (d, J¼2.4 Hz, 1H, H2), 7.40 (d,
J¼8.6 Hz, 2H, ArH), 7.47 (d, J¼8.6 Hz, 2H, ArH), 10.29 (br s, 1H, NH).
s, 1H, NH). 13C NMR (75 MHz, CDCl3):
d 55.2, 57.2, 64.9, 88.8, 95.4,
101.5, 110.3, 117.5, 121.4, 127.6, 130.6, 131.6, 132.5, 134.1, 139.4, 158.8,
160.4, 155.8. IR (KBr): nmax 3414, 2933, 2839, 1651, 1610, 1590, 1561,
1536, 1463, 1383, 1345, 1314, 1263, 1216, 1147, 1094, 1012, 979, 832,
797 cmꢁ1. UVevis (MeOH): lmax 307 nm ( 20,226 cmꢁ1 Mꢁ1), 283
3
(18,746), 238 (41,345). HRMS (ESIþ): found m/z 394.0810, [MþNa]þ;
C20H1835ClNNaO4 required 394.0822.
4.1.38. N-Allyl-4,6-dimethoxy-2,3-diphenyl-1H-indole-7-carbox-
amide (29). Indole 27a (2.348 g, 4.95 mmol) and allyl amine
(2.2 mL, 0.029 mol) were heated at reflux in THF (25 mL) for 3 h. The
reaction mixture was quenched with water (80 mL) and the
resulting precipitate collected to give the title compound 29 as
a white solid (1.496 g, 73%). Mp 188e190 ꢀC. Found: C, 75.67; H,
5.99; N, 6.86%. C26H24N2O3 requires: C, 75.71; H, 5.86; N, 6.79%. 1H
4.1.34. 3-(4-Chlorophenyl)-4,6-dimethoxy-7-trichloroacetylindole
(27c). This compound was prepared by the same method as com-
pound 27a, from indole 15c (1.08 g, 3.74 mmol), trichloroacetyl
chloride (2.0 mL, 17.9 mmol) and 1,2-dichloroethane (10 mL).
Chromatography (SiO2, 50% DCM/hexane) gave the title compound
27c as a yellow solid (0.352 g, 22%). Mp 174e175 ꢀC. Lit.27 mp
NMR (300 MHz, CDCl3):
d 3.76 (s, 3H, OCH3), 4.04 (s, 3H, OCH3),
178 ꢀC. 1H NMR (300 MHz, CDCl3):
d
3.93 (s, 3H, OCH3), 3.99 (s, 3H,
4.12e4.16 (m, 2H, H30), 5.18 (dd, J¼10.3, 1.5 Hz, 1H, H50), 5.29 (dd,
J¼17.2, 1.5 Hz, 1H, H50), 5.95e6.07 (m, 1H, H40), 6.23 (s, 1H, H5),
7.19e7.40 (m, 10H, ArH), 8.20 (br s, 1H, NH), 11.32 (br s, 1H, NH). 13C
OCH3), 6.22 (s, 1H, H5), 7.07 (d, J¼2.4 Hz, 1H, H2), 7.34 (d, J¼8.7 Hz,
2H, ArH), 7.47 (d, J¼8.4 Hz, 2H, ArH), 10.29 (br s, 1H, NH).
NMR (75 MHz, CDCl3): d 41.9, 55.7, 57.3, 88.1, 97.8, 114.0, 114.3, 115.7,
4.1.35. Allyl
4,6-dimethoxy-2,3-diphenyl-1H-indole-7-carboxylate
126.3, 127.4, 127.7, 128.4, 128.6, 131.9, 132.9, 133.7, 135.3, 136.4,
138.9, 156.9, 157.9, 167.9. IR (KBr): nmax 3412, 3358, 3060, 2941,
2842, 1630, 1597, 1530, 1503, 1463, 1449, 1426, 1359, 1335, 1252,
1232, 1187, 1150, 1116, 988, 918, 755, 699 cmꢁ1. UVevis (MeOH):
(28a). A mixture of indole 27a (2.44 g, 5.14 mmol), allyl alcohol
(2.1 mL, 30.8 mmol) and potassium hydroxide (0.58 g, 10.4 mmol)
in THF (30 mL) was heated at reflux for 2 h. The reaction mixture
was quenched with water (80 mL) and the resulting precipitate
collected to give the title compound 28a as a white solid (1.84 g,
86%). Mp 137e139 ꢀC. Found: C, 75.37; H, 5.72; N, 3.35%. C26H23NO4
requires: C, 75.53; H, 5.61; N, 3.39%. 1H NMR (300 MHz, CDCl3):
lmax 332 nm (3 M
23,128 cmꢁ1 ꢁ1), 317 (23,084), 248 (37,417). MS
(ESIþ): m/z 435.13, [MþNa]þ.
4.1.39. (1-Allyl-4,6-dimethoxy-2,3-diphenyl-1H-indol-7-yl)(2H-pyr-
rol-1-yl)methanone (33). This compound was prepared by the
same method as compound 21b, from indole 31 (0.476 g,
0.97 mmol), Grubbs’ catalyst (second gen, 5e10 mol %) and
degassed toluene (15 mL). Chromatography (SiO2, DCM) gave the
title compound 33 as an off white solid (0.367 g, 82%). Mp
d
3.78 (s, 3H, OCH3), 3.99 (s, 3H, OCH3), 4.92 (dt, J¼3.8, 1.4 Hz, 2H,
H30), 5.31 (dd, J¼10.5, 1.5 Hz, 1H, H50), 5.53 (dd, J¼17.1, 1.5 Hz, 1H,
H50), 6.01 (m, 1H, H40), 6.24 (s, 1H, H5), 7.31 (m, 10H, ArH), 10.34 (br
s, 1H, NH). 13C NMR (75 MHz, CDCl3):
d 55.2, 57.2, 64.8, 88.9, 94.9,
113.1, 114.4, 117.5, 126.1, 127.0, 127.3, 127.7, 128.4, 131.3, 132.4, 132.6,
132.6, 135.6, 138.5, 159.2, 160.2, 166.9. IR (KBr): nmax 3406, 3059,
2996, 2841, 1661, 1644, 1597, 1550, 1465, 1392, 1359, 1263, 1222,
1180, 1172, 1150, 1106, 990, 799, 752, 698 cmꢁ1. UVevis (MeOH):
198e200 ꢀC. 1H NMR (300 MHz, CDCl3):
d 3.78 (s, 3H, OCH3),
3.91e3.97 (m, 1H, H200), 3.94 (s, 3H, OCH3), 4.21e4.27 (m, 1H, H200),
4.39e4.50 (m, 2H, H10, 500), 4.58 (dd, J¼17.2, 1.0 Hz, 1H, H30), 4.94
(dd, J¼10.6, 1.0 Hz, 1H, H30), 5.00e5.06 (m, 1H, H500), 5.67e5.76 (m,
2H, H20, H300), 5.90e5.92 (m,1H, H400), 6.35 (s,1H, H5), 7.15e7.27 (m,
lmax 338 nm (3 M
17,296 cmꢁ1 ꢁ1), 314 (16,910), 248 (26,599). MS
(ESIþ): m/z 436.12, [MþNa]þ.
10H, ArH). 13C NMR (75 MHz, CDCl3):
d 46.3, 53.1, 54.5, 55.2, 57.1,
4.1.36. Allyl 3-(4-bromophenyl)-4,6-dimethoxy-1H-indole-7-carbox-
ylate (28b). This compound was prepared by the same method as
compound 28a, from indole 27b (0.848 g, 1.77 mmol), allyl alcohol
(0.7 mL, 0.010 mol), potassium hydroxide (0.20 g, 3.56 mmol) and
THF (20 mL). The title compound 28b was obtained as a pale yellow
solid (0.583 g, 79%). Mp 139e141 ꢀC. Found: C, 57.84; H, 4.39; N,
3.28%. C20H18BrNO4 requires: C, 57.71; H, 4.36; N, 3.36%. 1H NMR
88.6, 103.3, 113.2, 113.9, 115.6, 125.2, 125.3, 125.5, 126.5, 127.7, 127.8,
131.2, 131.3, 131.8, 133.4, 135.0, 135.6, 137.9, 152.9, 155.2, 166.7. IR
(KBr): nmax 3052, 2958, 2972, 2859, 1634, 1614, 1584, 1449, 1429,
1345, 1258, 1212, 1165, 1118, 1040, 911, 760, 693 cmꢁ1. UVevis
(MeOH): lmax 302 nm (3 M
12,646 cmꢁ1 ꢁ1), 239 (32,415). HRMS
(ESIþ): found m/z 465.2175, [MþH]þ; C30H29N2O3 required
465.2178.
(300 MHz, CDCl3): d 3.89 (s, 3H, OCH3), 3.99 (s, 3H, OCH3), 4.89 (dt,
J¼5.3, 1.5 Hz, 2H, H30), 5.30 (dd, J¼10.5, 1.5 Hz, 1H, H50), 5.50 (dd,
J¼18.8, 1.5 Hz, 1H, H50), 6.03e6.16 (m, 1H, H40), 6.28 (s, 1H, H5), 7.09
(d, J¼2.3 Hz, 1H, H2), 7.43 (d, J¼8.7 Hz, 2H, ArH), 7.48 (d, J¼8.7 Hz,
Acknowledgements
We thank the University of New South Wales and the Australian
Research Council for their financial support.
2H, ArH), 10.3 (br s, 1H, NH). 13C NMR (75 MHz, CDCl3):
d
55.1, 57.2,
64.9, 88.8, 89.1, 95.4, 110.3, 117.5, 119.7, 121.4, 130.6, 131.0, 132.5,
134.6, 139.4, 158.8, 160.4, 167.0. IR (KBr): nmax 3415, 2959, 2936,
2841, 1660, 1604, 1588, 1539, 1463, 1389, 1348, 1315, 1262, 1216,
Supplementary data
1150, 1083, 1006, 979, 800 cmꢁ1. UVevis (MeOH): lmax 306 nm (
3
Supplementary data associated with this article can be found in
the online version at doi:10.1016/j.tet.2011.04.019.
20,889 cmꢁ1
M
ꢁ1), 237 (41,097). MS (ESIþ): m/z 439.99, [MþNa]þ.

4102
K. Wood et al. / Tetrahedron 67 (2011) 4093e4102
15. van Wijngaarden, I.; Hamminga, D.; van Hes, R.; Standaar, P. J.; Tipker, J.; Tulp,
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