Selective 5-exo-dig cyclization of in situ synthesized N-Boc-2-aminophenyl ethoxyethynyl carbenols: Synthesis of multifunctional indoles and their derivatives

Article abstract of DOI:10.1002/adsc.201301002

A method to prepare 3-substituted-2-formylindole derivatives from N-Boc-ortho-aminoaryl ketones and ethoxyacetylene through a cascade of reactions in a single operation that included a nucleophile-triggered 5-exo-dig cyclization and an acid-mediated 1,3-allyl alcohol isomerization (1,3-AAI) is described. A variety of aryl, vinyl and alkynyl groups can be introduced at C-3 of indole-2-carboxaldehyde while having a high functional group compatibility. The 3-alkynyl adducts, which are highly valuable substrates for diversity-oriented synthesis, can be further transformed to useful carboline and carbazole derivatives through novel pathways.

Full text of DOI:10.1002/adsc.201301002

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DOI: 10.1002/adsc.201301002
Selective 5-exo-dig Cyclization of in Situ Synthesized
N-Boc-2-aminophenyl Ethoxyethynyl Carbenols: Synthesis of
Multifunctional Indoles and Their Derivatives
Nuligonda Thirupathi,a Yalla Kiran Kumar,a Ruchir Kant,b
and Maddi Sridhar Reddya,c,*
a
Medicinal & Process Chemistry Division, CSIR – Central Drug Research Institute, BS-10/1, Sector 10, Jankipuram
extension, Sitapur Road, P.O. Box 173, Lucknow – 226031, India
E-mail: msreddy@cdri.res.in or sridharreddymaddi@yahoo.com
Molecular and Structural Biology Division, CSIR – Central Drug Research Institute, BS-10/1, Sector 10, Jankipuram
b
extension, Sitapur Road, P.O. Box 173, Lucknow – 226031, India
Academy of Scientific and Innovative Research, New Delhi – 110001, India
c
Received: November 10, 2013; Revised: January 10, 2014; Published online: April 9, 2014
CDRI Communication No. 8624.
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201301002.
Abstract: A method to prepare 3-substituted-2-for- while having a high functional group compatibility.
mylindole derivatives from N-Boc-ortho-aminoaryl The 3-alkynyl adducts, which are highly valuable
ketones and ethoxyacetylene through a cascade of substrates for diversity-oriented synthesis, can be fur-
reactions in a single operation that included a nucleo- ther transformed to useful carboline and carbazole
phile-triggered 5-exo-dig cyclization and an acid- derivatives through novel pathways.
mediated 1,3-allyl alcohol isomerization (1,3-AAI) is
described. A variety of aryl, vinyl and alkynyl groups Keywords: alkynes; carbazoles; carbolines; cycliza-
can be introduced at C-3 of indole-2-carboxaldehyde tion; indoles
Introduction
efforts have been made over the years to develop syn-
thetic accesses to indoles,[2,6] the number of methods
Electrophilic cyclizations of functionalized alkynes allowing the efficient and selective synthesis of poly-
have come under increasing scrutiny in recent years substituted indoles with a good functional group toler-
as efficient and convergent strategies for a wide varie- ance remains limited.
ty of hetero- and carbocyclic compounds.[1–4] An
Various methods using transition metal-catalyzed
ample amount of research has been dedicated to find- cyclizations of functionalized alkynes for the synthesis
ing a variety of nucleophilic centers for the cyclization of variety of indole derivatives have been reported in
using a broad range of catalytic systems that included the recent past.[2] One of the few elegant approaches
transition metal-based catalysts, Lewis and Brønsted is the synthesis of 3-aryl/alkylindole-2-carboxalde-
acids and electrophilic halogen sources. The mode of hydes 4, reported by Chan et al, through electrophilic
cyclization (exo-, endo-) and construction of varied cyclization of tosylaminophenyl ethynyl carbenols 2
ring sizes has also been widely studied. In continua- (prepared from 1) using Au catalyst 3 and NIS
tion of our interest in this area of research,[3] we (Scheme 1).[6] We herein report a relatively easier
herein report a synthesis of 3-substituted 2-formylin- method for the synthesis of 3-aryl/vinyl/alkynylindole-
dole derivatives straightaway from readily available 2-carboxaldehydes 6 (from 5) in a single pot without
Boc-protected ortho-aminoaryl ketones through using any metal catalyst. As a complement, the 3-al-
a metal/catalyst-free, nucleophile-triggered cycliza- kynylindole-2-carboxaldehydes synthesized by our
tion. The indole moiety is a widely occurring subunit method can be further transformed to interesting
in a large number of natural products and has gained (biological, medicinal and material aspects) b-carbo-
lots of attention due to its wide range of biological line and indolocarbazole derivatives by novel ap-
and medicinal properties.[5] While several consequent proaches.
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Scheme 1. Synthesis of indole-2-carboxaldehydes through 5-exo-dig cyclizations.
Results and Discussion
1,3-AAIs in acidic medium have recently been report-
ed by Gabriel et al.[8] Thus, the reaction was quenched
As part of our previous works, we required a substrate slowly with dilute HCl and left at room temperature
7 which we planned to synthesize by addition of for 20 min. As expected, a clean formation of the
ethoxyacetylide to Boc-protected 2-aminobenzophe- product was observed in the crude reaction material
none 5a (Scheme 2). Surprisingly, a distinct compound and the subsequent silica gel chromatography yielded
8, formed through an in situ 5-exo-dig cyclization,[7] the required product in 74% yield.
was observed as a single product in the crude material
Although the present 5-exo-dig cyclization of 5a
after a water work-up. No trace of 7 was observed. In- compared to the 6-endo-dig cyclization[3c] of its tosyl
tramolecular cyclizations onto alkynes in non-metallic and acetyl counterparts seems to be contrasting, the
and non-acidic medium (nucleophile-triggered) are exo/endo selectivity has been shown to be highly sen-
not very common.[4] To our further surprise, we ob- sitive to various factors like nucleophility and size of
tained
a
clean 3-arylindole-2-carboxaldehyde 6a nucleophile, nature of alkyne (terminal or internal),
(albeit in low yield of 45%) after column chromatog- solvent, reagent, etc.[9] Although the detailed reasons
raphy on silica gel. The acidic nature of silica might for the selective cyclization remain elusive in the pres-
have induced the 1,3-allyl alcohol isomerization (1,3- ent case, we presume that the size and electronic
AAI). We became curious to know whether this could nature of the nucleophile combine for a kinetic con-
be developed as a general method for the synthesis of trol for 5-exo-dig-cyclization while supported by the
the privileged scaffold by carrying out 1,3-AAI in the thermodynamic stability of the incurring alkoxy vinyl
same reaction pot and by improving the yield. Such carbanion (vide infra).
Having non-metallic and one-pot conditions in
hand for the synthesis of indole-2-carboxaldehyde, we
next set out to investigate its generality. Various start-
ing materials 5a–r were prepared by Boc protection
of the readily available 2-aminobenzophenones[10] and
subjected to the one-pot addition/cyclization reaction
(Table 1). As is evident from Table 1 (5a–r to 6a–r),
the method is highly general withstanding various
electron-poor and electron-rich pendant groups. Vari-
ous halogen groups either on the core part or the
pendant phenyl ring at pro-C-3 were well tolerated
(5b–k to 6b–k). Electron-poor nitro substituted 5q
was also smoothly converted to corresponding prod-
uct 6q in 85% yield. Electron-rich methoxy-substitut-
ed substrates equally reacted to afford the corre-
sponding products 6n–p in 68–80% yield. Heteroaryl
groups also could be installed as in the case of prod-
uct 6r obtained from 5r. However, the reaction did
not work on the Boc-protected aminoacetophenone
Scheme 2. Synthesis of 6a from 5a via 8.
where we supposed to get 3-methylindole-2-carboxal-
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Selective 5-exo-dig Cyclization of in Situ Synthesized N-Boc-2-aminophenyl
Table 1. Synthesis of indole-2-carboxaldehydes 6 through 5-exo-dig cyclization of 5.[a]
[a]
1 mmol of compound in 8 mL THF was reacted with 4 equiv. of ethoxyacetylide for 8 h from À788C to room temperature.
12 mL of 1N HCl were used to quench the reaction at 08C.
dehyde. We next became interested to verify whether cyclization of the substrate (vide infra). The reaction
we can install a vinyl group (an additional adjacent was also equally viable for the alkyl and sensitive
functional group), instead of an aryl group, at C-3 of TMS-substituted alkynyl substrates (5v–x) to produce
indole by choosing 5s and 5t as starting materials the corresponding products (6v–x) in good to moder-
using the present method; 5s and 5t were prepared ate (69–73%) yields. In this way, an additional func-
from readily available 10[13] via Grignard addition and tional group for further modification is provided
MnO2-mediated oxidation. Pleasingly, both 5s and 5t apart from the aldehyde function at C-2. It should be
gave the corresponding products (6s and 6t) in 60 and particularly noted that the alkyne functionality may
68% yields, respectively (Scheme 3).
not survive in the general metal-mediated electrophil-
In the same line, our curiosity turned on the instal- ic cyclizations.[14]
lation of an alkynyl moiety (at C-3) to obtain 3-alky-
We then explored the utility of these 2,3-bifunction-
nylindole-2-carboxaldehydes. ortho-Alkynylaryl alde- al molecules (6u–y) for the novel synthesis of carbo-
hydes are currently highly explored for various kinds line and indolocarbazole derivatives. These annulated
of cyclizations to obtain diverse carbo- and heterocy- polyheterocyles have drawn much attention due to
clic compounds.[11,12] The alkynyl substrates 5u–x were their ubiquitous core structure, present in numerous
prepared from 10[13] via Grignard addition and oxida- biologically active natural products, pharmaceutically
tion (Scheme 3). Initially, we tested the reaction on important compounds and synthetic compounds with
5u which, to our pleasure, smoothly provided the ex- various material properties.[15] When 6u was treated
pected 6u in 72% yield. Of note is the selective cycli- with 5 equiv. of NH4OAc in MeCN[11f] for 12 h at
zation onto the ethoxyalkyne moiety in the presence 808C, the 3-phenylcarboline 11a was obtained in 78%
of a non-alkoxyalkynyl group. This reveals that the yield (Scheme 3). The reaction equally permitted the
thermodynamic stability of the incurring alkoxy vinyl synthesis of unsubstituted 11c and alkyl-substituted
carbanion also contributes for the selective 5-exo-dig 11b from the corresponding substrates 6y and 6w, re-
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Scheme 3. Synthesis of 3-alkenyl-/alkynylindole derivatives and their further conversion to carboline and carbazole deriva-
tives.
spectively. Earlier, such conversion was achieved by that provides 2-formyl-3-substituted indole derivatives
Larock et al. in two steps via tert-butylimine forma- in moderate to good yields for a variety of substrates
tion followed by CuI-mediated electrophilic cycliza- under mild conditions that did not require any metal
tion.[16] We next used 6u for the intermolecular oxida- or harsh reagents for cyclization and subsequent 1,3-
tive annulation[12] with N-methylindole using catalytic AAI. 3-Alkynylindole derivatives, prepared in this
CuACHTUNGTRENNUNG(OTf)2 in DCE at 558C for 6 h to obtain indolo- method, are further used to identify concise ap-
ACHTUNGTRENNUNG
[3,2-b]carbazole derivative 12,[17] an analogue of the proaches to b-carboline and indolocarbazole deriva-
natural product/AhR agonist 13.[15h,18] Boc deprotec- tives.
tion of 12 using TBAF[19] (other available acidic re-
agents were not very productive) yielded 14 which al-
lowed us to obtain clean crystals to unambiguously
Experimental Section[21]
confirm its structure by X-ray crystallography
(Scheme 3).[20]
General Information
All reagents and solvents were purchased from commercial
sources and used without purification. NMR spectra were
1
Conclusions
recorded with a 300 or 400 MHz spectrometer for H NMR,
75 or 100 MHz for 13C NMR. Chemical shifts are reported
In conclusion, we have demonstrated a convenient
relative to the residual signals of tetramethylsilane in CDCl3
1
and operationally straightforward synthetic method or deuterated solvent CDCl3/DMSO-d6 for H and 13C NMR
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Selective 5-exo-dig Cyclization of in Situ Synthesized N-Boc-2-aminophenyl
spectra. Multiplicities are reported as follows: singlet (s),
doublet (d), doublet of doublets (dd), doublet of triplets
(dt), triplet (t), quartet (q), multiplet (m). HR-MS were re-
corded by using a QTof mass spectrometer. Column chro-
matography was performed with silica gel (100–200 mesh)
as the stationary phase. All reactions were monitored by
using TLC. The purity and characterization of compounds
were further established by using HR-MS.
before drying over Na2SO4. After removal of the solvent
under vacuum the crude product was purified on silica
(using 5% EtOAc/hexane) to afford 5x as a yellow solid;
yield: 1.08 g (76%).
General Procedure C for the Synthesis of Indole-2-
carbaldehydes 6a–x from 5a–x taking the Synthesis of
6a as an Example
General Procedure A for the Synthesis of Alkenones
(5s, 5t) taking the Synthesis of 5s as an Example
n-BuLi (1.6M in THF, 2.50 mL, 4 equiv.) was added slowly
to ethoxyacetylene (40 wt/vol% in hexane, 0.70 mL,
4 equiv.) in THF (4 mL) at À788C and the mixture was
stirred at the same temperature for 2 h and at 08C for an-
other 2 h. Then the reaction mixture was re-cooled to
À788C before adding 5a (297 mg in 4 mL THF, 1 mmol,
1 equiv.) to it. The mixture was then stirred at À788C for
1 h and at room temperature for 2 h. Then 1N HCl was
added to the reaction mixture at 08C and stirred for 30 min
at room temperature. The mixture was extracted with
EtOAc (2ꢁ10 mL) and the combined extracts were washed
with brine (15 mL) and then dried over Na2SO4. After re-
moval of the solvent under vacuum the crude product was
purified on silica (using 3% EtOAc/hexane) to afford 6a as
a yellow gum; yield: 237 mg (74%).
Vinylmagnesium bromide (1M in THF, 4.5 mL, 4.5 mmol,
1 equiv.) was slowly added to the mixture of 10 (1 g,
4.5 mmol, 1 equiv.) in 10 mL THF under a nitrogen atmos-
phere at À408C. After 30 min of stirring at the same tem-
perature the reaction mixture was diluted with saturated
NH4Cl solution. The mixture was extracted with EtOAc (2ꢁ
25 mL) and the combined extracts were washed with brine
(15 mL) and dried over Na2SO4. After removal of the sol-
vent under vacuum the crude product was filtered on
a short pad of silica and the filtrate was concentrated under
vacuum. Then the crude material was dissolved in 20 mL of
DCM and activated MnO2 (7.74 g, 90 mmol, 20 equiv.) was
added to the mixture. Then the reaction mixture was stirred
for 2 h at room temperature, filtered through a celite pad
and concentrated under reduced pressure. The crude prod-
uct was purified on silica (using 5% EtOAc/hexane) to
afford 5s as a colorless oil; yield: 0.66 g (60%).
General Procedure D for the Synthesis of b-
Carbolines (11a–c) taking the Synthesis of 11a as an
Example
An oven-dried, 10-mL, round-bottom flask was charged
with 6u (345 mg, 1 mmol, 1 equiv.), NH4OAc (385 mg,
5 mmol, 5 equiv.) and 4 mL CH3CN. The reaction mixture
was stirred at 808C for 12 h. The reaction mixture was
cooled to room temperature, diluted with water (10 mL)
and extracted with EtOAc (2ꢁ10 mL). The combined ex-
tracts were washed with brine (15 mL) and dried over
Na2SO4. After removal of the solvent under vacuum the
crude product was purified on silica (using 4% EtOAc/
hexane) to afford 11a as a brown solid; yield: 267 mg
(78%).
tert-Butyl 2-(4-bromobenzoyl)phenylcarbamate (5b): 5b
was obtained from the corresponding 2-aminobenzophe-
none[10] as a yellow solid; yield:0.80 g (59%); mp 130–
1328C; Rf =0.60 (SiO2, 10% EtOAc/90% hexanes);
1H NMR (400 MHz, CDCl3): d=9.97 (bs, 1H), 8.42(d,
J=8.4 Hz, 1H), 7.63–7.45 (m, 6H), 6.99 (t, J=7.5 Hz, 1H),
1.52 (s, 9H); 13C NMR (100 MHz, CDCl3): d=198.2, 153.0,
141.5, 137.6, 134.5, 133.3, 131.6, 131.5, 127.4, 122.5, 120.9,
120.1, 80.8, 28.4; IR: n=3684, 1724, 1582, 1156, 929,
629 cmÀ1; HR-MS (ESI-TOF): m/z=398.0362, calcd. for
C18H18BrNNaO3 [M+Na]+: 398.0368.
tert-Butyl 2-(4-fluorobenzoyl)phenylcarbamate (5c): 5c
was obtained from the corresponding 2-aminobenzophe-
none[10] as a white solid; yield: 0.87 g (60%); mp 90–928C;
Rf =0.65 (SiO2, 10% EtOAc/90% hexanes); 1H NMR
(300 MHz, CDCl3): d=9.87 (bs, 1H), 8.40 (d, J=8.5 Hz,
1H), 7.76–7.71 (m, 2H), 7.56–7.45 (m, 2H), 7.15 (t, J=
8.5 Hz, 2H), 7.00 (t, J=7.3 Hz, 1H), 1.51 (s, 9H); 13C NMR
(100 MHz, CDCl3): d=197.7, 166.6, 164.1, 153.0, 141.3,
135.0, 134.2, 133.1, 132.7, 132.6, 122.9, 120.8, 120.2, 115.6,
115.4, 80.7, 28.3; IR: n=3430, 1999, 1448, 1216, 1097,
General Procedure B for the Synthesis of Alkynones
(5u–x) taking the Synthesis of 5u as an Example
n-BuLi (1.6M in THF, 11.2 mL, 4 euiv.q) was slowly added
to phenylacetylene (1.82 g, 18.0 mmol, 4 equiv.) in THF
(15 mL) at À788C and the mixture was stirred at the same
temperature for 20 min and at room temperature for anoth-
er 1 h. Then the reaction mixture was re-cooled to À788C
before adding 10 (1 g in 15 mL THF, 4.5 mmol, 1 equiv.) to
it. The mixture was then warmed to À408C and stirred for
1 h at the same temperature before diluting it with saturated
NH4Cl solution. The mixture was extracted with EtOAc (2ꢁ
25 mL) and the combined extracts were washed with brine
(15 mL) and dried over Na2SO4. After removal of the sol-
vent under vacuum the crude product was filtered on
a short pad of silica and filtrate was concentrated under
vacuum. Then the crude material (except for 5x synthesis)
was dissolved in 20 mL of DCM and activated MnO2
(7.74 g, 90 mmol, 20 equiv.) was added to the mixture. Then
the reaction mixture was stirred for 2 h at room tempera-
ture, filtered through a celite pad, and then concentrated
under reduced pressure. The crude product was purified on
silica (using 5% EtOAc/hexane) to afford 5u as a yellow
solid; yield: 0.98 g (68%).
In case of the synthesis of 5x synthesis, the crude product,
after the TMS acetylide addition reaction, was dissolved in
10 mL DCM and Dess–Martin periodinane (2.28 g,
5.4 mmol, 1.2 equiv,) in 15 mL of DCM was added at 08C.
After stirring at the same temperature for 20 min the reac-
tion mixture was diluted with hypo solution, extracted with
DCM (2ꢁ25 mL) and the combined extracts were washed
with saturated NaHCO3 solution followed by brine (15 mL)
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669 cmÀ1; HR-MS (ESI-TOF): m/z=338.1164, calcd. for
C18H18FNNaO3 [M+Na]+: 338.1168.
tert-Butyl 2-(3-fluoro-4-methoxybenzoyl)phenylcarbamate
(5k): 5k was obtained from the corresponding 2-aminoben-
zophenone as a yellow gum; yield: 0.81 g (58%); Rf =0.50
(SiO2, 10% EtOAc/90% hexanes); 1H NMR (400 MHz,
CDCl3): d=9.68 (s, 1H), 8.36 (d, J=8.3 Hz, 1H), 7.56–7. 48
(m, 4H), 7.03–6.99 (m, 2H), 3.97 (s, 3H), 1.53 (s, 9H);
13C NMR (100 MHz, CDCl3): d=196.6, 152.9, 151.6, 151.5,
150.4, 140.8, 133.7, 132.6, 131.3,131.2, 127.7, 127.7, 123.1,
120.8, 120.1, 117.8, 117.6, 112.1, 80.6, 56.3, 28.2; IR: n=3850,
3745, 1640, 1022, 928 cmÀ1; HR-MS (ESI-TOF): m/z=
368.1272, calcd. for C19H20FNNaO4 [M+Na]+: 368.1274.
tert-Butyl 2-(4-methylbenzoyl)phenylcarbamate (5l): 5l
was obtained from the corresponding 2-aminobenzophenone
as a light yellow solid; yield: 0.88 g (60%); mp 120–1228C;
Rf =0.64 (SiO2, 10% EtOAc/90% hexanes); 1H NMR
(400 MHz, CDCl3): d=10.26 (bs, 1H), 8.28 (s, 1H), 7.67–
7.65 (m, 2H), 7.56 (t, J=7.4 Hz, 1H), 7.46 (t, J=7.4 Hz,
2H), 7.41 (d, J=8.0 Hz, 1H), 6.79 (d, J=8.0 Hz, 1H), 2.41
(s, 3H), 1.52 (s, 9H); 13C NMR (100 MHz, CDCl3): d=
199.2, 153.2, 145.6, 141.7, 139.2, 134.0, 132.0, 129.7, 128.2,
121.7, 120.1, 120.0, 80.5, 28.3, 22.2; IR: n=3021, 1723, 1524,
1321, 1259, 1049, 670 cmÀ1; HR-MS (ESI-TOF): m/z=
334.1422, calcd. for C19H21NNaO3 [M+Na]+: 334.1419.
tert-Butyl 2-benzoyl-4-methylphenylcarbamate: (5m): 5m
was obtained from the corresponding 2-aminobenzophe-
none[6] as a yellow solid; yield: 0.95 g (65%); mp 98–1008C;
Rf =0.65 (SiO2, 10% EtOAc/90% hexanes); 1H NMR
(400 MHz, CDCl3): d=9.85 (s, 1H), 8.27 (d, J=8.5 Hz, 1H),
7.69 ( d, J=1.5 Hz, 1H), 7.60–7.56 (m, 1H), 7.48 (t, J=
7.5 Hz, 2H), 7.37–7.33 (m, 2H), 7.29 (s, 1H), 2.27 (s, 3H),
1.51 (s, 9H); 13C NMR (100 MHz, CDCl3): d=199.4, 153.2,
139.0, 138.9, 134.9, 133.6, 132.3, 130.3, 130.0, 129.5, 128.3,
123.1, 120.1, 80.5, 28.4, 20.7; IR: n=3437, 2401, 1422, 1095,
928, 670 cmÀ1; HR-MS (ESI-TOF): m/z=334.1422, calcd.
for C19H21NNaO3 [M+Na]+: 334.1419.
tert-Butyl 2-(2-fluorobenzoyl)phenylcarbamate (5e): 5e
was obtained from the corresponding 2-aminobenzophe-
none[10] as a yellow solid; yield: 0.82 g (56%); mp 90–928C;
Rf =0.60 (SiO2, 10% EtOAc/90% hexanes); 1H NMR
(400 MHz, CDCl3): d=10.63 (s, 1H), 8.50 (d, J=8.5 Hz,
1H), 7.57–7.42 (m, 4H), 7.26 (t, J=8.2 Hz, 1H), 7.16 (t, J=
9.3 Hz, 1H), 6.98–6.94 (m, 1H) 1.54 (s, 9H); 13C NMR
(100 MHz, CDCl3): d=196.6, 153.0, 142.3, 135.4, 134.2,
132.9, 132.8, 130.2, 129.9, 128.3, 124.3, 124.2, 121.9, 120.9,
119.2, 116.4, 116.2, 80.8, 28.3; IR: n=3855, 3694, 3402, 1736,
1447, 1149, 770 cmÀ1; HR-MS (ESI-TOF): m/z=338.1164,
calcd. for C18H18FNNaO3 [M+Na]+: 338.1168.
tert-Butyl 2-benzoyl-4-chlorophenylcarbamate (5f): 5f was
obtained from the corresponding 2-aminobenzophenone as
a yellow solid; yield: 0.85 g (60%); mp 88–908C; Rf =0.60
(SiO2, 10% EtOAc/90% hexanes); 1H NMR (400 MHz,
CDCl3): d=9.84 (s, 1H), 8.39 (d, J=9.2 Hz, 1H), 7.70–7.68
(m, 2H), 7.63–7.59 (m, 1H), 7.52–7.47 (m, 4H), 1.51 (s,
9H); 13C NMR (100 MHz, CDCl3): d=198.0, 152.8, 139.9,
138.1, 133.8, 132.8, 132.5, 129.9, 128.5, 125.9, 124.0, 121.5,
81.0, 28.3; IR: n=3375, 2401, 1642, 1397, 1052, 949,
529 cmÀ1; HR-MS (ESI-TOF): m/z=354.0867, calcd. for
C18H18ClNNaO3 [M+Na]+: 354.0873.
tert-Butyl 4-chloro 2-(2-chlorobenzoyl)phenylcarbamate
(5h): 5h was obtained from the corresponding 2-aminoben-
zophenone as a light yellow solid; yield: 0.82 g (60%); mp
88–908C; Rf =0.65 (SiO2, 10% EtOAc/90% hexanes);
1H NMR (400 MHz, CDCl3): d=10.69 (bs, 1H), 8.54 (d, J=
9.1 Hz, 1H), 7.50–7.44 (m, 3H), 7.41–7.37 (m, 1H), 7.32–
7.30 (m, 1H) 7.26 (d, J=2.2 Hz, 1H), 1.55 (s, 9H);
13C NMR (100 MHz, CDCl3): d=197.7, 152.9, 141.4, 138.3,
135.5, 133.4, 131.5, 131.0, 130,3, 128.8, 126.9, 125.9, 122.0,
120.7, 81.2, 28.3; IR: n=3684, 1726, 1576, 1316, 1104, 930,
501 cmÀ1; HR-MS (ESI-TOF): m/z=388.0476, calcd. for
C18H17Cl2NNaO3 [M+Na]+: 388.0483.
tert-Butyl 4-bromo-2-(2-fluorobenzoyl)phenylcarbamate
(5i): 5i was obtained from the corresponding 2-aminobenzo-
phenone[10] as a light yellow solid; yield: 0.80 g (60%); mp
98–1008C; Rf =0.65 (SiO2, 10% EtOAc/90% hexanes);
1H NMR (400 MHz, CDCl3): d=10.46 (s, 1H), 8.43 (d, J=
9.0 Hz, 1H), 7.61 (dd, J=9.0, 2.2 Hz, 1H), 7.58–7.54 (m,
2H), 7.47–7.43 (m, 1H), 7.30 (d, J=7.4 Hz, 1H), 7.19 (t, J=
9.0 Hz, 1H), 1.53 (s, 9H); 13C NMR (100 MHz, CDCl3): d=
195.4, 160.8, 158.3, 152.8, 141.2, 137.9, 136.0, 133.5, 133.4,
130.3, 127.2, 127.0, 124.5, 123.5, 121.2, 116.7, 116.5, 113.1,
81.2, 28.3; IR: n=3850, 3745, 1640, 1022, 928 cmÀ1; HR-MS
(ESI-TOF): m/z=416.0263, calcd. for C18H17BrFNNaO3
[M+Na]+: 416.0274.
tert-Butyl
2-(4-methoxybenzoyl)-5-methylphenylcarba-
mate (5n): 5n was obtained from the corresponding 2-ami-
nobenzophenone as a yellow solid; yield: 0.94 g (67%); mp
110–1128C; Rf =0.60 (SiO2, 10% EtOAc/90% hexanes);
1H NMR (400 MHz, CDCl3): d=9.51 (s, 1H), 8.20 (d, J=
8.5 Hz, 1H), 7.72–7.69 (m, 2H), 7.31–7.23 (m, 2H), 6.95–
6.92 (m, 2H), 3.87 (s, 3H), 2.26 (s, 3H), 1.48 (s, 9H);
13C NMR (100 MHz, CDCl3): d=197.7, 163.3, 153.2, 138.2,
134.2, 132.9, 132.6, 131.3, 130.3, 124.1, 120.3, 113.6, 80.4,
55.6, 28.4, 20.7; IR: n=3684, 2401, 1307, 1034, 626 cmÀ1
;
HR-MS (ESI-TOF): m/z=364.1517, calcd. for C20H23NNaO4
[M+Na]+: 364.1525.
tert-Butyl 4,5-dimethoxy-2-(4-methylbenzoyl)phenylcarba-
mate (5o): 5o was obtained from the corresponding 2-ami-
nobenzophenone[9] as a yellow gum; yield: 0.95 g (70%);
Rf =0.45 (SiO2, 10% EtOAc/90% hexanes); 1H NMR
(400 MHz, CDCl3): d=10.54 (s, 1H), 8.15 (s, 1H),7.58 (d,
J=8.0 Hz, 2H), 7.27 (d, J=8.0 Hz, 2H), 7.03 (s, 1H), 4.01
(s, 3H), 3.71 (s, 3H), 2.44 (s, 3H), 1.52 (s, 9H); 13C NMR
(100 MHz, CDCl3): d=197.7, 154.2, 153.4, 142.5, 142.3,
138.4, 136.9, 129.7, 129.0, 116.3, 114.6, 102.7, 80.5, 56.3, 56.3,
28.4, 21.7; IR: n=3684, 2401, 1307, 1034, 626 cmÀ1; HR-MS
(ESI-TOF): m/z=394.1628, calcd. for C21H25NNaO5 [M+
Na]+: 394.1630.
tert-Butyl 4-chloro-2-(2-fluorobenzoyl)phenylcarbamate
(5j): 5j was obtained from the corresponding 2-aminobenzo-
phenone as a white solid; yield: 0.81 g (58%); mp 94–968C;
Rf =0.60 (SiO2, 10% EtOAc/90% hexanes); 1H NMR
(400 MHz, CDCl3): d=10.45 (s, 1H), 8.49 (d, J=9.0 Hz,
1H), 7.58–7.40 (m, 4H), 7.28 (t, J=7.5 Hz, 1H), 7.19 (t, J=
9.0 Hz, 1H), 1.53 (s, 9H); 13C NMR (100 MHz, CDCl3): d=
195.5, 160.8, 158.3, 152.9, 140.8, 135.1, 133.5, 133.4, 133.1,
133.0, 130.3, 127.2, 127.1, 126.0, 124.5, 124.5, 123.1, 120.9,
116.7, 116.581.2, 28.3; IR: n=3021, 1577, 1410, 1156, 1025,
929 cmÀ1; HR-MS (ESI-TOF): m/z=372.0793, calcd. for
C18H17ClFNNaO3 [M+Na]+: 372.0779.
tert-Butyl 2-benzoyl-4,5-dimethoxyphenylcarbamate (5p):
5p was obtained from the corresponding 2-aminobenzophe-
none[9] as a yellow gum; yield: 0.94 g (68%); Rf =0.40 (SiO2,
1828
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Adv. Synth. Catal. 2014, 356, 1823 – 1834

FULL PAPERS
Selective 5-exo-dig Cyclization of in Situ Synthesized N-Boc-2-aminophenyl
10% EtOAc/90% hexanes); 1H NMR (400 MHz, CDCl3):
d=10.62 (s, 1H), 8.16 (s, 1H), 7.66–7.64 (m, 2H), 7.57–7.53
(m, 1H), 7.49–7.45 (m, 2H), 7.01 (s, 1H), 4.01 (s, 3H), 3.69
(s, 3H), 1.52 (s, 9H); 13C NMR (100 MHz, CDCl3): d=
198.0, 154.4, 153.2, 142.3, 139.6, 138.6, 131.7, 129.3, 128.2,
116.3, 114.1, 102.5, 80.4, 56.2, 28.3; IR: n=3682, 2401, 1643,
1340, 927, 629 cmÀ1; HR-MS (ESI-TOF): m/z=380.1467,
calcd. for C20H23NNaO5 [M+Na]+: 380.1474.
tert-Butyl 2-benzoyl-4-nitrophenylcarbamate (5q): 5q was
obtained from the corresponding 2-aminobenzophenone as
a yellow solid; yield: 0.77 g (55%); mp 130–1328C; Rf =0.55
(SiO2, 20% EtOAc/80% hexanes); 1H NMR (400 MHz,
CDCl3): d=10.37 (s, 1H), 8.68 (d, J=9.4 Hz, 1H), 8.44 ( d,
J=2.5 Hz, 1H), 8.36 (dd, J=9.4, 2.5 Hz, 1H), 7.71–7.64 (m,
3H), 7.53 (t, J=7.5 Hz, 2H)1.54 (s, 9H); 13C NMR
(100 MHz, CDCl3): d=197.8, 152.2, 147.0, 140.4, 137.6,
133.3, 129.9, 129.1, 128.9, 128.8, 121.5, 119.7, 82.2, 28.2; IR:
n=3398, 1644, 1414, 1253, 1050, 927 cmÀ1; HR-MS (ESI-
TOF): m/z=365.1102, calcd. for C18H18N2NaO5 [M+Na]+:
365.1113.
1H), 8.36(dd, J=8.0, 1.5 Hz, 1H), 7.69–7.67 (m, 2H), 7.59–
7.55 (m, 1H), 7.51–7.47 (m, 1H), 7.45–7.41 (m, 2H), 7.10 (t,
J=7.7 Hz, 1H), 1.54 (s, 9H); 13C NMR (100 MHz, CDCl3):
d=180.6, 153.0, 142.8, 135.9, 134.6, 133.0, 130.9, 128.8, 121.7,
121.2, 120.0, 118.8, 94.2, 87.1, 80.8, 28.3; IR: n=3684, 3433,
2401, 1442, 1153, 628 cmÀ1; HR-MS (ESI-TOF): m/z=
344.1260, calcd, for C20H19NNaO3 [M+Na]+: 344.1263.
tert-Butyl 2-hex-2-ynoylphenylcarbamate (5v): 5v was ob-
tained from 10[13] (1 g, 4.5 mmol) following general proce-
dure B as a colorless solid; yield: 1.02 g, (79%); mp 87–
1
898C; Rf =0.60 (SiO2, 10% EtOAc/90% hexanes); H NMR
(400 MHz, CDCl3): d=10.75 (s, 1H), 8.45 (d, J=8.5 Hz,
1H), 8.24 (dd, J=7.9, 1.4 Hz, 1H), 7.55–7.50 (m, 1H), 7.06–
7.02 (m, 1H), 2.48 (t, J=7.0 Hz, 2H), 1.73–1.67 (m, 2H),
1.51 (s, 9H), 1.07 (t, J=7.4 Hz, 3H); 13C NMR (75 MHz,
CDCl3): d=180.8, 153.0, 142.7, 135.5, 134.7, 121.7,
121.0,118.6, 97.8, 80.7, 80.1, 28.3, 21.3, 21.2,13.6; IR: n=
3683, 2401, 1608, 1424, 1096, 928, 671, 497 cmÀ1; HR-MS
(ESI-TOF): m/z=310.1409, calcd. for C17H21NNaO3 [M+
Na]+: 310.1419.
tert-Butyl 2-(5-methylthiophene-3-carbonyl)phenylcarba-
mate (5r): 5r was obtained from the corresponding 2-amino-
benzophenone[9] as a yellow gum; yield: 0.87 g (60%); Rf =
tert-Butyl 2-non-2-ynoylphenylcarbamate (5w): 5w was
obtained from 10[13] (1 g, 4.5 mmol) following general proce-
dure B as a colorless gum; yield: 0.65 g (75%); Rf =0.60
(SiO2, 10% EtOAc/90% hexanes); 1H NMR (400 MHz,
CDCl3): d=10.75 (s, 1H), 8.45 (d, J=8.5 Hz, 1H), 8.24 (dd,
J=7.9, 1.3 Hz, 1H), 7.53 (t, J=7.9 Hz, 1H), 7.06–7.02 (m,
1H), 7.29 (s, 1H), 2.50 (t, J=7.0 Hz, 2H), 1.70–1.63 (m,
2H), 1.55–1.50 (m, 15H), 0.90 (t, J=6.6 Hz, 3H); 13C NMR
(75 MHz, CDCl3): d=180.9, 153.0, 142.7, 135.6, 134.7, 121.8,
121.0, 118.7, 98.0, 80.7, 80.0, 31.3, 28.4, 28.3, 27.8, 22.5, 19.3,
1
0.60 (SiO2, 10% EtOAc/90% hexanes); H NMR (400 MHz,
CDCl3): d=9.38 (s, 1H), 8.32 (d, J=8.4 Hz, 1H), 7.73 ( dd,
J=7.7, 1.2 Hz, 1H), 7.52–7.48 (m, 1H), 7.38 (d, J=3.7 Hz,
1H), 7.04 (t, J=7.7 Hz, 1H), 6.82 (d, J=3.7 Hz, 1H), 2.57
(s, 3H), 1.49 (s, 9H); 13C NMR (100 MHz, CDCl3): d=
189.3, 153.0, 151.1, 142.1, 140.0, 136.4, 133.3, 131.5, 126.9,
124.1, 121.1, 120.3, 80.6, 28.3, 16.1; IR: n=3390, 2928, 1614,
1444, 1157, 670 cmÀ1; HR-MS (ESI-TOF): m/z=340.0987,
calcd. for C17H19NNaO3S [M+Na]+: 340.0983.
tert-Butyl 2-acryloylphenylcarbamate (5s): 5s was ob-
tained from 10[13] (1 g, 4.50 mmol) following general proce-
dure A as a colorless oil; yield: 0.66 g (60%); Rf =0.70
(SiO2, 10% EtOAc/90% hexanes); 1H NMR (400 MHz,
CDCl3): d=10.69 (s, 1H), 8.45 (d, J=8.5 Hz, 1H), 7.83 (dd,
J=7.9, 1.1 Hz, 1H), 7.52 (t, J=7.9 Hz, 1H), 7.23–7.16 (m,
1H), 7.03 (t, J=7.9 Hz, 1H), 6.41 (dd, J=16.9, 1.5 Hz, 1H),
5.91 (dd, J=10.6, 1.5 Hz, 1H), 1.52 (s, 9H); 13C NMR
(100 MHz, CDCl3): d=193.6, 153.0, 142.1, 134.8, 133.3,
131.1, 130.2, 121.9, 121.0, 119.5, 80.5, 28.3; IR: n=3682,
2400, 1582, 1474, 1368, 1306, 848, 496 cmÀ1; HR-MS (ESI-
TOF): m/z=270.1101, calcd. for C14H17NNaO3 [M+Na]+:
270.1106.
tert-Butyl 2-methacryloylphenylcarbamate (5t): 5t was ob-
tained from 10[13] (1 g, 4.50 mmol) following general proce-
dure A as a colorless oil; yield: 0.68 g (58%); Rf =0.68
(SiO2, 10% EtOAc/90% hexanes); 1H NMR (400 MHz,
CDCl3): d=9.81 (s, 1H), 8.34 (d, J=8.4 Hz, 1H), 7.65 (dd,
J=7.9, 1.5 Hz, 1H), 7.50–7.46 (m, 1H), 7.00–6.96 (m, 1H),
5.79 (s, 1H), 5.45 (s, 1H), 2.07 (s, 3H), 1.51 (s, 9H);
13C NMR (100 MHz, CDCl3): d=201.1, 153.1, 144.6, 141.1,
134.0, 132.8, 125.7, 122.7, 120.7, 119.9, 80.6, 28.4, 19.0; IR:
n=3682, 2929, 1613, 1268, 1160, 928, 670 cmÀ1; HR-MS
(ESI-TOF): m/z=284.1258, calcd. for C15H19NNaO3 [M+
Na]+: 284.1263.
14.0; IR: n=3434, 2344, 1618, 1579, 1419, 928, 627 cmÀ1
;
HR-MS (ESI-TOF): m/z=330.2057, calcd, for C20H28NO3
[M+H]+: 330.2069.
tert-Butyl 2-[3-(trimethylsilyl)propioloyl]phenylcarbamate
(5x): 5x was obtained from 10[13] (1 g, 4.5 mmol) following
general procedure B as a yellow solid; yield: 1.08 g, (76%);
mp 88–908C; Rf =0.50 (SiO2, 10% EtOAc/90% hexanes);
1H NMR (400 MHz, CDCl3): d=10.68 (s, 1H), 8.45 (d, J=
8.5 Hz, 1H), 8.25 (dd, J=7.9, 1.3 Hz, 1H), 7.59 (t, J=
8.5 Hz, 1H), 7.06 (t, J=7.9 Hz, 1H), 1.52 (s, 9H), 0.31 (s,
9H); 13C NMR (100 MHz, CDCl3): d=180.2, 153.0, 142.9,
135.9, 134.8, 121.4, 121.2,118.7, 101.7, 100.9, 80.8, 28.3,
À0.63); IR: n=3429, 3021, 1729, 1403, 1152, 852, 669 cmÀ1
C17H23NNaO3Si [M+Na]+: 340.1345.
tert-Butyl 2-formyl-3-phenyl-1H-indole-1-carboxylate
;
HR-MS
(ESI-TOF):
m/z=340.1337,
calcd.
for
(6a): 6a was obtained from 5a[10] (297 mg, 1 mmol) following
general procedure C as a colorless gum; yield: 237 mg
(74%); Rf =0.58 (SiO2, 10% EtOAc/90% hexanes);
1H NMR (400 MHz, CDCl3): d=10.10 (s, 1H), 8.17 (d, J=
8.5 Hz, 1H), 7.63–7.46 (m, 7H), 7.30 (t, J=7.4 Hz, 1H), 1.69
(s, 9H); 13C NMR (100 MHz, CDCl3): d=182.5, 149.8, 137.5,
133.1, 132.4, 130.9, 130.7, 128.6, 128.6, 128.4, 128.2, 123.7,
122.1, 115.2, 85.2, 28.2; IR: n=3399, 1733, 1215, 1083,
763 cmÀ1; HR-MS (ESI-TOF): m/z=344.1251, calcd. for
C20H19NNaO3 [M+Na]+: 344.1263.
tert-Butyl
3-(4-bromophenyl)-2-formyl-1H-indole-1-car-
tert-Butyl 2-(3-phenylpropioloyl)phenylcarbamate (5u):
5u was obtained from 10[13] (1 g, 4.5 mmol) following general
procedure B as a yellow solid: yield: 0.98 g (68%); mp 80–
828C; Rf =0.70 (SiO2, 10% EtOAc/90% hexanes); H NMR
(400 MHz, CDCl3): d=10.78 (s, 1H), 8.49 (d, J=8.4 Hz,
boxylate (6b): 6b was obtained from 5b (375 mg, 1 mmol)
following general procedure C as a white solid; yield:
311 mg (78%); mp 130–1328C; Rf =0.60 (SiO2, 10% EtOAc/
90% hexanes); 1H NMR (400 MHz, CDCl3): d=10.15 (s,
1H), 8.17 (d, J=8.5 Hz, 1H), 7.62 (d, J=8.2 Hz, 2H), 7.56–
1
Adv. Synth. Catal. 2014, 356, 1823 – 1834
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1829

FULL PAPERS
Nuligonda Thirupathi et al.
7.50 (m, 2H), 7.44 (d, J=8.2 Hz, 2H), 7.30 (t, J=7.5 Hz,
1H), 1.70 (s, 9H); 13C NMR (100 MHz, CDCl3): d=182.7,
149.8, 137.2, 132.4, 132.3, 131.6, 130.7, 130.1, 128.7, 128.1,
124.0, 122.9, 121.9, 115.5, 85.7, 28.1; IR: n=3855, 3659, 2400,
116.9, 85.9, 28.0; IR: n=3889, 3787, 2400, 1385, 1095,
626 cmÀ1; HR-MS (ESI-TOF): m/z=422.0356, calcd. for
C20H18BrNNaO3 [M+Na]+: 422.0368.
tert-Butyl
5-chloro-3-(2-chlorophenyl)-2-formyl-1H-
1150, 1027, 929, 669 cmÀ1
;
HR-MS (ESI-TOF): m/z=
422.0356, calcd. for C20H18BrNNaO3 [M+Na]+: 422.0368.
tert-Butyl 3-(4-fluorophenyl)-2-formyl-1H-indole-1-car-
indole-1-carboxylate (6h): 6h was obtained from 5h (365 mg,
1 mmol) following general procedure C as a brown gum;
yield: 280 mg (72%); Rf =0.65 (SiO2, 10% EtOAc/90% hex-
1
boxylate (6c): 6c was obtained from 5c (315 mg, 1 mmol)
following general procedure C as a yellow solid; yield:
264 mg (78%); mp 118–1208C; Rf =0.58 (SiO2, 10% EtOAc/
90% hexanes); 1H NMR (300 MHz, CDCl3): d=10.13 (s,
1H), 8.18 (d, J=8.5 Hz, 1H), 7.58–7.49 (m, 4H), 7.30 (t, J=
7.4 Hz, 1H), 7.18 (t, J=8.5 Hz, 2H), 1.70 (s, 9H); 13C NMR
(75 MHz, CDCl3): d=182.7, 164.6, 161.3, 149.8, 137.2, 132.6,
132.5, 131.2, 128.7, 128.3, 127.0, 127.0, 123.9, 122.0, 115.6,
115.5, 115.3, 85.6, 28.1; IR: n=3787, 3659, 2400, 1605, 1372,
1075, 627 cmÀ1; HR-MS (ESI-TOF): m/z=362.1162, calcd.
for C20H18FNNaO3 [M+Na]+: 362.1168.
anes); H NMR (300 MHz, CDCl3): d=10.21 (s, 1H), 8.12
(d, J=8.9 Hz, 1H), 7.54–7.25 (m, 6H), 1.70 (s, 9H);
13C NMR (75 MHz, CDCl3): d=182.9, 149.5, 135.1, 134.0,
132.3, 130.4, 130.1, 130.6, 129.7, 129.5, 128.8, 127.3, 126.9,
121.4, 117.0, 28.2; IR: n=3855, 3680, 2400, 1653, 1151, 929,
669 cmÀ1; HR-MS (ESI-TOF): m/z=412.0469, calcd. for
C20H17Cl2NNaO3 [M+Na]+: 412.0483.
tert-Butyl
5-bromo-3-(4-fluorophenyl)-2-formyl-1H-
indole-1-carboxylate (6i): 6i was obtained from 5i (393 mg,
1 mmol) following general procedure C as a yellow solid;
yield: 283 mg (68%); mp 130–1328C; Rf =0.68 (SiO2,10%
EtOAc/90% hexanes); 1H NMR (300 MHz, CDCl3): d=
10.24 (s, 1H), 8.07 (d, J=9.3 Hz, 1H), 7.60 (s, 2H), 7.44 (t,
J=7.4 Hz, 2H), 7.31–7.19 (m, 2H), 1.70 (s, 9H); 13C NMR
(75 MHz, CDCl3): d=182.8, 161.7, 158.4, 149.4, 135.5, 133.7,
132.4, 132.3, 131.3, 130.8, 130.7, 129.9, 124.4, 124.3, 124.2,
123.2, 118.9, 118.7, 117.2, 116.2, 116.0, 86.3, 28.1; IR: n=
3855, 3659, 1618, 1384, 1073, 929, 627 cmÀ1; HR-MS (ESI-
TOF): m/z=440.0265, calcd. for C20H17BrFNNaO3 [M+
Na]+: 440.0274.
tert-Butyl
3-(2-chlorophenyl)-2-formyl-1H-indole-1-car-
boxylate (6d): 6d was obtained from 5d[21] (331 mg, 1 mmol)
following general procedure C as a yellow gum; yield:
252 mg (71%); Rf =0.60 (SiO2, 10% EtOAc/90% hexanes);
1H NMR (400 MHz, CDCl3): d=10.22 (s, 1H), 8.18 (d, J=
8.4 Hz, 1H), 7.54–7.49 (m, 2H), 7.40–7.38 (m, 4H), 7.28 (d,
J=7.6 Hz, 1H) 1.71 (s, 9H); 13C NMR (100 MHz, CDCl3):
d=183.0, 149.8, 136.9, 134.0, 133.0, 132.3, 131.0, 129.9, 129.8,
128.7, 128.5, 128.3, 126.7, 123.8, 122.0, 115.7, 85.7, 28.2; IR:
n=3402, 3020, 1681, 1317, 1122, 669 cmÀ1; HR-MS (ESI-
TOF): m/z=378.0865, calcd. for C20H18ClNNaO3 [M+Na]+:
378.0873.
tert-Butyl
5-chloro-3-(2-fluorophenyl)-2-formyl-1H-
indole-1-carboxylate (6j): 6j was obtained from 5j (349 mg,
1 mmol) following general procedure C as a yellow solid;
yield: 279 mg (75%); mp 114–1168C; Rf =0.60 (SiO2, 10%
EtOAc/90% hexanes); 1H NMR (400 MHz, CDCl3): d=
10.24 (s, 1H), 8.12 (d, J=8.9 Hz, 1H), 7.47–7.42 (m, 4H),
7.29 (d, J=7.4 Hz, 1H), 7.21 (t, J=8.9 Hz, 1H), 1.70 (s,
9H); 13C NMR (100 MHz, CDCl3): d=182.9, 161.3, 158.9,
149.4, 135.2, 133.9, 132.4, 130.8, 130.7, 129.7, 129.4, 128.7,
124.2, 123.3, 121.3, 118.9, 118.7, 116.9, 116.2, 116.0, 86.3,
tert-Butyl
3-(2-fluorophenyl)-2-formyl-1H-indole-1-car-
boxylate (6e): 6e was obtained from 5e (315 mg, 1 mmol)
following general procedure C as a yellow solid; yield:
237 mg (70%); mp 115–1178C; Rf =0.50 (SiO2, 10% EtOAc/
90% hexanes); 1H NMR (400 MHz, CDCl3): d=10.24 (s,
1H), 8.18 (d, J=8.5 Hz, 1H), 7.53–7.41 (m, 4H), 7.31–7.19
(m, 3H), 1.70 (s, 9H); 13C NMR (75 MHz, CDCl3): d=
183.0, 161.8, 158.5, 149.8, 137.0, 133.1, 132.5, 130.7, 130.5,
130.4, 128.5, 128.3, 124.7, 124.1, 124.0, 123.9, 122.0, 119.5,
119.3, 116.1, 115.8, 115.6, 85.7, 28.1; IR: n=3402, 3020, 1681,
1317, 1122, 669 cmÀ1; HR-MS (ESI-TOF): m/z=362.1160,
calcd. for C20H18FNNaO3 [M+Na]+: 362.1168.
28.1; IR: n=3855, 3681, 2400, 1420, 1073, 928, 627 cmÀ1
HR-MS (ESI-TOF): m/z=396.0767, calcd. for
C20H17ClFNNaO3 [M+Na]+: 396.0779.
tert-Butyl 3-(3-fluoro-4-methoxyphenyl)-2-formyl-1H-
;
indole-1-carboxylate (6k): 6k was obtained from 5k (345 mg,
1 mmol) following general procedure C as a yellow solid;
yield: 265 mg (72%); mp 125–1278C; Rf =0.68 (SiO2, 20%
EtOAc/80% hexanes); 1H NMR (300 MHz, CDCl3): d=
10.13 (s, 1H), 8.17 (d, J=8.4 Hz, 1H), 7.61 (d, J=7.9 Hz,
1H), 7.52 (t, J=7.9 Hz, 1H), 7.35–7.26 (m, 3H), 7.08 (t, J=
8.4 Hz, 1H), 3.96 (s, 3H), 1.69 (s, 9H); 13C NMR (75 MHz,
CDCl3): d=182.6, 153.6, 150.4, 149.8, 148.1, 137.2, 132.4,
131.0, 130.9, 128.7, 127.1, 127.0, 123.9, 123.7, 120.2, 118.5,
118.3, 115.4, 113.2, 113.2, 85.5, 56.3, 28.0; IR: n=3780, 3402,
2401, 1514, 1028, 928, 670 cmÀ1; HR-MS (ESI-TOF): m/z=
392.1272, calcd. for C21H20FNNaO4 [M+Na]+: 392.1274.
tert-Butyl 2-formyl-3-para-tolyl-1H-indole-1-carboxylate
(6l): 6l was obtained from 5l (311 mg, 1 mmol) following
general procedure C as a colorless gum; yield: 257 mg
(77%); Rf =0.65 (SiO2, 10% EtOAc/90% hexanes);
1H NMR (400 MHz, CDCl3): d=10.02 (s, 1H), 7.99 (s, 1H),
7.57–7.45 (m, 6H), 7.12 (d, J=8.0 Hz, 1H), 2.52 (s, 3H),
1.67 (s, 9H); 13C NMR (75 MHz, CDCl3): d=182.4, 150.0,
139.6, 138.4, 134.0, 132.1, 131.2, 130.7, 128.7, 128.5, 126.0,
125.6, 121.9, 115.2, 85.1, 28.0, 22.4; IR: n=3399, 1733, 1215,
tert-Butyl 5-chloro-2-formyl-3-phenyl-1H-indole-1-carbox-
ylate (6f): 6f was obtained from 5f (331 mg, 1 mmol) follow-
ing general procedure C as a brown solid: yield: 241 mg
(68%); mp 100–1028C; Rf =0.65 (SiO2, 10% EtOAc/90%
hexanes); 1H NMR (400 MHz, CDCl3): d=10.10 (s, 1H),
8.11 (d, J=8.8 Hz, 1H), 7.63–7.37 (m, 7H), 1.68 (s, 9H);
13C NMR (75 MHz, CDCl3): d=182.5, 149.5, 135.7, 133.2,
131.8, 130.6, 130.4, 129.6, 129.4, 128.9, 128.6, 121.5, 116.6,
85.9, 28.0; IR: n=3855, 3681, 2400, 1549, 1317, 928, 757,
627 cmÀ1; HR-MS (ESI-TOF): m/z=378.0858, calcd. for
C20H18ClNNaO3 [M+Na]+: 378.0873.
tert-Butyl 5-bromo-2-formyl-3-phenyl-1H-indole-1-carbox-
ylate (6g): 6g was obtained from 5g[10] (375 mg, 1 mmol) fol-
lowing general procedure C as a yellow solid; yield: 319 mg
(80%); mp 105–1078C; Rf =0.64 (SiO2, 20% EtOAc/80%
hexanes); 1H NMR (400 MHz, CDCl3): d=10.69 (s, 1H),
8.05 (d, J=8.9 Hz, 1H), 7.71 (d, J=1.6 Hz, 1H), 7.58 (dd,
J=8.9, 1.8 Hz, 1H), 7.53–7.46 (m, 5H), 1.68 (s, 9H);
13C NMR (100 MHz, CDCl3): d=182.4, 149.5, 136.1, 133.1,
131.6, 131.5, 130.6, 130.4, 129.9, 128.9, 128.6, 124.6, 117.1,
1830
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ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2014, 356, 1823 – 1834

FULL PAPERS
Selective 5-exo-dig Cyclization of in Situ Synthesized N-Boc-2-aminophenyl
1083, 763 cmÀ1; HR-MS (ESI-TOF): m/z=358.1411, calcd.
for C21H21NNaO3 [M+Na]+: 358.1419.
HR-MS
(ESI-TOF):
m/z=389.1112,
calcd.
for
C20H18N2NaO5 [M+Na]+: 389.1113.
tert-Butyl
2-formyl-5-methyl-3-phenyl-1H-indole-1-car-
tert-Butyl 2-formyl-3-(5-methylthiophene-2-yl)-1H-indole-
1-carboxylate (6r): 6r was obtained from 5r (317 mg,
1 mmol) following general procedure C as a yellow-colored
gum; yield: 221 mg (65%); Rf =0.63 (SiO2, 10% EtOAc/
90% hexanes); 1H NMR (400 MHz, CDCl3): d=10.15 (s,
1H), 8.14 (d, J=8.5 Hz, 1H), 7.91 (d, J=7.9 Hz, 1H), 7.51
(t, J=7.9 Hz, 1H), 7.32 (t, J=7.9 Hz, 1H), 7.28 (d, J=
3.4 Hz, 1H), 6.86 (d, J=3.4 Hz, 1H), 2.57 (s, 3H), 1.67 (s,
9H); 13C NMR (75 MHz, CDCl3): d=182.1, 149.7, 142.7,
137.5, 132.5, 130.5, 128.9, 128.7, 128.0, 125.9, 125.7, 123.8,
122.5, 115.2, 85.4, 28.0, 15.4; IR: n=3855, 3694, 1638, 1219,
1096, 772 cmÀ1; HR-MS (ESI-TOF): m/z=364.0992, calcd.
for C19H19NNaO3S [M+Na]+: 364.0983.
boxylate (6m): 6m was obtained from 5m (311 mg, 1 mmol)
following general procedure C as a light yellow solid; yield:
247 mg (74%); mp 110–1128C; Rf =0.68 (SiO2, 10% EtOAc/
90% hexanes); 1H NMR (400 MHz, CDCl3): d=10.08 (s,
1H), 8.04 (d, J=8.5 Hz, 1H), 7.56–7.45 (m, 5H), 7.36–7.33
(m, 2H), 2.41 (s, 3H), 1.68 (s, 9H); 13C NMR (100 MHz,
CDCl3): d=182.6, 149.9, 135.9, 133.4, 132.9, 132.6, 131.2,
130.7, 130.4, 128.5, 128.4, 121.6, 115.0, 85.1, 28.0, 21.3; IR:
n=3855, 3694, 3019, 1626, 1318, 1140, 668 cmÀ1; HR-MS
(ESI-TOF): m/z=358.1409, calcd. for C21H21NNaO3 [M+
Na]+: 358.1419.
tert-Butyl
2-formyl-3-(4-methoxyphenyl)-6-methyl-1H-
indole-1-carboxylate (6n): 6n was obtained from 5n (341 mg,
1 mmol) following general procedure C as a light yellow
solid: yield: 292 mg (80%); mp 115–1178C; Rf =0.50 (SiO2,
20% EtOAc/80% hexanes); 1H NMR (400 MHz, CDCl3):
d=10.07 (s, 1H), 8.03 (d, J=8.6 Hz, 1H), 7.51 (d, J=8.6 Hz,
2H), 7.38 (s, 1H), 7.33 (d, J=8.6 Hz, 1H), 7.03 (d, J=
8.6 Hz, 2H), 3.88 (s, 3H), 2.42 ( s, 3H), 1.68 (s, 9H);
13C NMR (100 MHz, CDCl3): d=182.6, 160.0, 150.0, 135.9,
133.3, 132.9, 132.4, 132.0, 130.3, 128.6, 123.3, 121.7, 115.0,
113.9, 85.0, 55.4, 28.0, 21.3; IR: n=3402, 1731, 1674, 1079,
669 cmÀ1; HR-MS (ESI-TOF): m/z=388.1521, calcd. for
C22H23NNaO4 [M+Na]+: 388.1525.
tert-Butyl 2-formyl-3-vinyl-1H-indole-1-carboxylate (6s):
6s was obtained from 5s (247 mg, 1 mmol) following general
procedure C as a colorless gum; yield: 162 mg (60%); Rf =
1
0.65 (SiO2, 10% EtOAc/90% hexanes); H NMR (400 MHz,
CDCl3): d=10.41 (s, 1H), 8.19 (d, J=8.4 Hz, 1H), 7.95 (d,
J=8.0 Hz, 1H), 7.53–7.49 (m, 1H), 7.34 (t, J=8.0 Hz, 1H),
7.29–7.24 (m, 1H), 6.01 (dd, J=11.6, 1.2 Hz, 1H), 5.69 (dd,
J=11.6, 1.2 Hz, 1H), 1.69 (s, 9H); 13C NMR (75 MHz,
CDCl3): d=184.6, 149.9, 137.3, 132.5, 128.4, 128.2, 127.5,
126.9, 124.0, 122.5, 121.3, 116.0, 85.8, 28.2; IR: n=3855,
3694, 3019, 1524, 1313, 1123, 669 cmÀ1; HR-MS (ESI-TOF):
m/z=294.1116, calcd. for C16H17NNaO3 [M+Na]+: 294.1106.
tert-Butyl 2-formyl-3-(prop-1-en-2-yl)-1H-indole-1-carbox-
ylate (6t): 6t was obtained from 5t (261 mg, 1 mmol) follow-
ing general procedure C as a colorless gum; yield: 193 mg
(68%); Rf =0.60 (SiO2, 10% EtOAc/90% hexanes);
1H NMR (400 MHz, CDCl3): d=10.29 (s, 1H), 8.12 (d, J=
8.5 Hz, 1H), 7.66 (d, J=7.9 Hz, 1H), 7.51–7.47 (m, 1H),
7.29 (t, J=7.9 Hz, 1H), 5.48 (t, J=1.6 Hz, 1H), 5.12 (t, J=
1.6 Hz, 1H), 2.17 (s, 3H), 1.68 (s, 9H); 13C NMR (100 MHz,
CDCl3): d=183.4, 150.0, 137.3, 136.5, 134.6, 132.0, 128.6,
127.9, 123.6, 122.1, 118.5, 115.6, 85.4, 28.2, 23.6; IR: n=3437,
2401, 1674, 1158, 927, 670 cmÀ1; HR-MS (ESI-TOF): m/z=
308.1263, calcd. for C17H19NNaO3 [M+Na]+: 308.1263.
tert-Butyl 2-formyl-5,6-dimethoxy-3-para-tolyl-1H-indole-
1-carboxylate (6o): 6o was obtained from 5o (371 mg,
1 mmol) following general procedure C as a brown solid:
yield: 276 mg (70%); mp 95–978C; Rf =0.54 (SiO2, 20%
1
EtOAc/80% hexanes); H NMR (400 MHz, CDCl3): d=9.93
(s, 1H), 7.71 (s, 1H), 7.45 (d, J=8.0 Hz, 2H), 7.32 (d, J=
8.0 Hz, 2H), 6.94 (s, 1H), 4.01 (s, 3H), 3.85 ( s, 3H), 2.45 (s,
3H), 1.67 (s, 9H); 13C NMR (75 MHz, CDCl3): d=181.5,
151.8, 150.0, 147.6, 138.5, 134.7, 133.3, 131.3, 130.3, 129.2,
128.3, 125.7, 120.7, 102.1, 97.6, 84.8, 56.2, 56.1, 27.9, 21.3;
IR: n=3413, 1731, 1661, 1381, 1224, 850, 667 cmÀ1; HR-MS
(ESI-TOF): m/z=418.1617, calcd. for C23H25NNaO5 [M+
Na]+: 418.1630.
tert-Butyl 2-formyl-5,6-dimethoxy-3-phenyl-1H-indole-1-
carboxylate (6p): 6p was obtained from 5p (357 mg, 1 mmol)
following general procedure C as a brown solid; yield:
259 mg (68%); mp 90–928C; Rf =0.60 (SiO2, 20% EtOAc/
80% hexanes); 1H NMR (400 MHz, CDCl3): d=9.94 (s,
1H), 7.72 (s, 1H), 7.56–7.46 (m, 5H), 6.92 (s, 1H), 4.01 (s,
3H), 3.85 ( s, 3H), 1.67 (s, 9H); 13C NMR (75 MHz, CDCl3):
d=181.6, 151.9, 150.0, 147.7, 134.5, 133.3, 131.5, 131.4, 130.5,
128.6, 128.6, 120.8, 102.0, 97.7, 85.0, 56.3, 56.2, 28.0; IR: n=
3855, 3681, 2400, 1619, 1143, 928, 669 cmÀ1; HR-MS (ESI-
TOF): m/z=404.1463, calcd. for C22H23NNaO5 [M+Na]+:
404.1474.
tert-Butyl 2-formyl-3-(phenylethynyl)-1H-indole-1-carbox-
ylate (6u): 6u was obtained from 5u (321 mg, 1 mmol) fol-
lowing general procedure C as a brown solid; yield: 248 mg
(72%); mp 96–988C; Rf =0.55 (SiO2, 10% EtOAc/90% hex-
1
anes); H NMR (400 MHz, CDCl3): d=10.42 (s, 1H), 8.14
(d, J=8.4 Hz, 1H), 7.89 (d, J=7.9 Hz, 1H), 7.68–7.65 (m,
2H), 7.54 (t, J=7.4 Hz, 1H), 7.40–7.38 (m, 4H), 1.70 (s,
9H); 13C NMR (75 MHz, CDCl3): d=181.8, 149.4, 137.3,
137.1, 132.1, 129.1, 129.0, 128.8, 128.5, 124.1, 122.8, 120.0,
115.8, 113.3, 98.6, 85.9, 80.7, 28.1; IR: n=3402, 3020, 2401,
1733, 1377, 1128, 929 cmÀ1; HR-MS (ESI-TOF): m/z=
368.1258, calcd. for C22H19NNaO3 [M+Na]+: 368.1263.
tert-Butyl 2-formyl-3-(pent-1-ynyl)-1H-indole-1-carboxyl-
ate (6v): 6v was obtained from 5v (287 mg, 1 mmol) follow-
ing general procedure C as a brown solid; yield: 227 mg
(73%); mp 114–1168C; Rf =0.60 (SiO2, 10% EtOAc/90%
hexanes); 1H NMR (400 MHz, CDCl3): d=10.31 (s, 1H),
8.10 (d, J=8.5 Hz, 1H), 7.77 (d, J=7.8 Hz, 1H), 7.50 (t, J=
8.5 Hz, 1H), 7.33 (t, J=7.8 Hz, 1H), 2.55 (t, J=7.0 Hz, 2H),
1.75–1.70 (m, 2H), 1.67 (s, 9H), 1.12 (t, J=7.4 Hz, 3H);
13C NMR (75 MHz, CDCl3): d=181.7, 149.4, 137.2, 137.2,
129.2, 129.0, 123.9, 122.0, 115.6, 114.7, 100.8, 85.6, 71.8, 28.0,
22.2, 22.1, 13.6; IR: n=3787, 3659, 3401, 1526, 1385, 928,
tert-Butyl 2-formyl-5-nitro-3-phenyl-1H-indole-1-carboxyl-
ate (6q): 6q was obtained from 5q (342 mg, 1 mmol) follow-
ing general procedure C as a yellow solid; yield: 311 mg
(85%); mp 225–2278C; Rf =0.60 (SiO2, 20% EtOAc/80%
hexanes); 1H NMR (300 MHz, CDCl3): d=10.10 (s, 1H),
8.52 (d, J=1.9 Hz, 1H), 8.37 (dd, J=9.2, 1.9 Hz, 1H), 8.27
(d, J=9.2 Hz, 1H), 7.64–7.45 (m, 5H), 1.70 (s, 9H);
13C NMR (75 MHz, CDCl3): d=182.1, 149.0, 144.5, 140.1,
134.5, 132.8, 130.6, 129.5, 129.4, 128.9, 128.1, 123.3, 118.7,
115.8, 87.0, 27.9; IR: n=3396, 1742, 1330, 1075, 703 cmÀ1
;
Adv. Synth. Catal. 2014, 356, 1823 – 1834
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1831

FULL PAPERS
Nuligonda Thirupathi et al.
757, 467 cmÀ1; HR-MS (ESI-TOF): m/z=334.1416, calcd.
for C19H21NNaO3 [M+Na]+: 334.1419.
116.7, 112.5, 84.7, 38.4, 31.9, 30.5, 29.2, 28.5, 22.7, 14.2; IR:
n=3855, 3658, 3019, 1626, 1325, 1095, 769, 669 cmÀ1; HR-
MS (ESI-TOF): m/z=353.2233, calcd. for C22H29N2O2 [M+
H]+: 353.2229.
tert-Butyl 2-formyl-3-(oct-1-ynyl)-1H-indole-1-carboxylate
(6w): 6w was obtained from 5w (329 mg, 1 mmol) following
general procedure C as a yellow-colored gum; yield: 247 mg
(70%); Rf =0.70 (SiO2, 10% EtOAc/90% hexanes);
1H NMR (400 MHz, CDCl3): d=10.30 (s, 1H), 8.09 (d, J=
8.5 Hz, 1H), 7.77 (d, J=7.5 Hz, 1H), 7.50 (t, J=7.5 Hz,
1H), 7.33 (t, J=7.5 Hz, 1H), 2.57 (t, J=7.2 Hz, 2H), 1.68–
1.65 (m, 11H), 1.36–1.33 (m, 6H), 0.91 (t, J=7.0 Hz, 3H);
13C NMR (75 MHz, CDCl3): d=181.6, 149.4, 137.2, 129.2,
129.2, 128.9, 123.9, 123.8, 121.9, 115.6, 101.0, 85.6, 71.6, 31.4,
28.6, 28.4, 28.0, 22.6, 20.1, 14.1; IR: n=3855, 3694, 3406,
1654, 1218, 1096, 772 cmÀ1; HR-MS (ESI-TOF): m/z=
376.1878, calcd. for C22H27NNaO3 [M+Na]+: 376.1889.
tert-Butyl 2-formyl-3-[(trimethylsilyl)ethynyl]-1H-indole-
1-carboxylate (6x): 6x was obtained from 5x (317 mg,
1 mmol) following general procedure C as a light yellow-col-
ored solid; yield: 235 mg (69%); mp 110–1128C; Rf =0.68
(SiO2, 5% EtOAc/95% hexanes); 1H NMR (400 MHz,
CDCl3): d=10.30 (s, 1H), 8.09 (d, J=8.5 Hz, 1H), 7.78 (d,
J=7.8 Hz, 1H), 7.53–7.48 (m, 1H), 7.37–7.35 (m, 1H), 1.66
(s, 9H), 0.32 (s, 9H); 13C NMR (100 MHz, CDCl3): d=
181.4, 149.2, 138.0, 137.1, 129.1, 128.8, 124.1, 122.0, 115.1,
113.5, 105.4, 95.2, 85.9, 28.0, 0.01; IR: n=3435, 1403, 1217,
1148, 848, 669 cmÀ1; HR-MS (ESI-TOF): m/z=364.1332,
calcd. for C19H23NNaO3Si [M+Na]+: 364.1345.
(Z)-tert-Butyl 2-(ethoxymethylene)-3-hydroxy-3-phenylin-
doline-1-carboxylate (8): yellow oil; yield: 72%; Rf =0.40
(SiO2, 20% EtOAc/80% hexanes); 1H NMR (400 MHz,
CDCl3): d=7.70 (d, J=8.1 Hz, 1H), 7.44 (d, J=7.1 Hz, 2H),
7.25–7.18 (m, 4H), 7.04 (d, J=7.3 Hz, 1H), 6.93 (t, J=
7.3 Hz, 1H), 5.78 (s, 1H), 3.79–3.70 (m, 2H), 1.50 (s, 9H),
1.19 (t, J=7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3): d=
151.2, 143.7, 142.2, 136.8, 136.4, 129.3, 127.9, 127.4, 126.6,
126.4, 123.9, 123.6, 116.1, 81.7, 80.5, 68.9, 28.2, 15.4; IR: n=
3431, 3019, 1732, 1401, 1150, 840, 701, 668 cmÀ1; HR-MS
(ESI-TOF): m/z=390.1677, calcd. for C22H25NNaO4 [M+
Na]+: 390.1681.
tert-Butyl 9H-pyridoACTHNUTRGNEUGN[3,4-b]indole-9-carboxylate (11c): 11c
was obtained from 6y (269 mg, 1 mmol) following general
procedure D as a brown solid; yield: 187 mg (70%); mp
128–1308C; Rf =0.43 (SiO2, 20% EtOAc/80% hexanes);
1H NMR (400 MHz, CDCl3): d=9.56 (s, 1H), 8.56 (d, J=
5.1 Hz, 1H), 8.39 (d, J=8.2 Hz, 1H), 8.04 (d, J=7.6 Hz,
1H), 7.87 (d, J=5.1 Hz, 1H), 7.61 (t, J=8.2 Hz, 1H), 7.41
(t, J=7.6 Hz, 1H), 1.77 (s, 9H); 13C NMR (100 MHz,
CDCl3): d=150.5, 142.9, 139.3, 138.5, 132.0, 129.8, 123.8,
123.5, 121.1, 116.7, 114.0, 85.0, 81.2, 28.4; IR: n=3436, 2401,
1518, 1264, 928, 670 cmÀ1
269.1281, calcd. for C16H17N2O2 [M+H]+: 269.1290.
; HR-MS (ESI-TOF): m/z=
tert-Butyl 12-Benzoyl-11-methylindolo
ACHTUNGTNER[NUNG 3,2-
b]carbazole-5(11H)-carboxylate (12)
AHCTUNGTRENNUNG
An oven-dried 10-mL round-bottom flask was charged with
6u (345 mg, 1 mmol, 1 equiv.), Cu(OTf)2 (10 mol% 36 mg),
AHCTUNGTRENNUNG
N-methylindole (158 mg, 1.2 mmol, 1.2 equiv.) and 8 mL of
1,2-dichloroethane.The reaction mixture was stirred at 608C
for 8 h, then cooled to room temperature, diluted with water
(10 mL) and extracted with DCM (2ꢁ10 mL). The com-
bined extracts were washed with brine (15 mL) and dried
over Na2SO4. After removal of the solvent under vacuum
the crude product was purified on silica (using 3% EtOAc/
hexane) to afford 12 as a yellow solid; yield: 284 mg (60%);
mp 210–2128C; Rf =0.45 (SiO2, 10% EtOAc/90% hexanes);
1H NMR (400 MHz, CDCl3): d=9.25 (s, 1H), 8.32 (d, J=
8.4 Hz, 1H), 8.23 (d, J=7.6 Hz, 1H), 7.96 (bs, 2H), 7.60–
7.48 (m, 3H), 7.45–7.25 (m, 5H), 7.09 (t, J=7.6 Hz, 1H),
3.60 (s, 3H), 1.85 (s, 9H); 13C NMR (100 MHz, CDCl3): d=
198.5, 151.4, 142.9, 139.6, 138.2, 134.8, 134.4, 132.8, 130.2,
129.3, 127.0, 126.6, 124.6, 124.2, 122.9, 122.9, 121.9, 121.8,
120.4, 119.3, 116.3, 115.1, 108.7, 108.5, 84.1, 32.0, 28.6; IR:
n=3684, 3433, 1522, 1421, 1030, 928, 627 cmÀ1; HR-MS
(ESI-TOF): m/z=475.2014, calcd. for C31H27N2O3 [M+H]+:
475.2022.
tert-Butyl 3-phenyl-9H-pyridoACTHNUTRGNEUGN[3,4-b]indole-9-carboxylate
(11a): 11a was obtained from 6u (345 mg, 1 mmol) following
general procedure D as a brown solid; yield: 267 mg (78%);
mp 115–1178C; Rf =0.65 (SiO2, 20% EtOAc/80% hexanes);
1H NMR (400 MHz, CDCl3): d=9.59 (s, 1H), 8.44 (d, J=
8.4 Hz, 1H), 8.29 (d, J=0.8 Hz, 1H), 8.10 (dd, J=7.1,
1.5 Hz, 3H), 7.63 (t, J=8.4 Hz, 1H), 7.52 (t, J=7.1 Hz, 2H),
7.45–7.40 (m, 2H), 1.80 (s, 9H); 13C NMR (100 MHz,
CDCl3): d=151.3, 150.5, 139.9, 139.8, 138.0, 134.0, 133.1,
129.9, 128.9, 128.5, 127.1, 124.1, 123.6, 121.0, 116.8, 110.8,
84.9, 28.5; IR: n=3405, 2929, 1728, 1534, 1326, 1152, 669
5-Methyl-5,11-dihydroindolo
yl(phenyl)methanone (14)
ACHTUNGTREN[NUNG 3,2-b]carbazol-6-
AHCTUNGTRENNUNG
TBAF (1M in THF, 1 mL, 1 mmol, 1 equiv.) was added was
added to the solution of 12 (474 mg,1 mmol,1 equiv.) in
5 mL of THF and the mixture was refluxed for 6 h. After
cooling down to room temperature the reaction mixture was
diluted with water and extracted with EtOAc (2ꢁ10 mL).
The combined extracts were washed with brine (15 mL) and
then dried over Na2SO4. After removal of the solvent under
vacuum the crude product was purified on silica (using 6%
EtOAc/hexane) to afford 14 as an yellow solid; yield:
228 mg (61%); mp 225–2278C; Rf =0.60 (SiO2, 15% EtOAc/
cmÀ1
C22H21N2O2 [M+H]+: 345.1603.
tert-Butyl 3-hexyl-9H-pyridoACTHNGUTRNE[NGU 3,4-b]indole-9-carboxylate
;
HR-MS (ESI-TOF): m/z=345.1594, calcd. for
(11b): 11b was obtained from 6w (353 mg, 1 mmol) follow-
ing general procedure D as a yellow-colored gum; yield:
245 mg (70%); Rf =0.60 (SiO2, 20% EtOAc/80% hexanes);
1H NMR (400 MHz, CDCl3): d=9.41 (s, 1H), 8.39 (d, J=
7.7 Hz, 1H), 8.00 (d, J=7.7 Hz, 1H), 7.70 (d, J=3.3 Hz,
1H), 7.60–7.56 (m, 1H), 7.40–7.36 (m, 1H), 2.93 (t, J=
7.4 Hz, 2H), 1.85–1.70 (m, 13H), 1.38–1.27 (m, 4H), 0.88 (t,
J=3.0 Hz, 3H); 13C NMR (100 MHz, CDCl3): d=155.8,
150.6, 139.7, 137.6, 133.2, 132.8, 129.7, 124.0, 123.4, 121.0,
1
85% hexanes); H NMR (400 MHz, DMSO-d6): d=11.49 (s,
1H), 8.43 (s, 1H), 8.40–8.33 (m, 1H), 7.94 (d, J=7.2 Hz,
2H), 7.73 (t, J=7.0 Hz, 1H), 7.61–7.50 (m, 5H), 7.41–7.32
(m, 2H), 7.30–7.24 (m, 1H), 6.93 (t, J=7.4 Hz, 1H), 3.57 (s,
3H); 13C NMR (100 MHz, CDCl3): d=198.8, 142.9, 141.5,
138.3, 134.5, 134.2, 133.6, 130.2, 129.1, 126.4, 126.0, 123.9,
122.2, 121.8, 120.2, 119.9, 119.0, 118.7, 115.1, 110.6, 108.5,
1832
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FULL PAPERS
Selective 5-exo-dig Cyclization of in Situ Synthesized N-Boc-2-aminophenyl
102.1, 32.2; IR: n=3020, 2400, 1731, 1518, 1462, 1322, 1115,
924, 624 cmÀ1; HR-MS (ESI-TOF): m/z=375.1482, calcd.
for C26H19N2O [M+H]+: 375.1497.
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Acknowledgements
NT and YKK thank CSIR for the Ph. D. fellowships. We
thank Dr. T. K. Chakraborty, Director CDRI, for the encour-
agement. We thank SAIF division CSIR-CDRI for the analyt-
ical support. We also thank Dr. Tejender S. Thakur of Molec-
ular and Structural Biology Division, CSIR-Central Drug Re-
search Institute for supervising the X-ray data collection and
structure determination of compound 14 in the paper. We
gratefully acknowledge the financial support by CSIR-Net-
work project ꢀBSC0102ꢁ (CSIR-CDRI-THUNDER) and by
DST under ꢀFast Track Proposal Scheme for Young Scien-
tistsꢁ (CS-399/2012).
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1834
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Adv. Synth. Catal. 2014, 356, 1823 – 1834