Palladium-Catalyzed Synthesis of Indolines from Aroyloxycarbamates through a Tandem Decarboxylative Amination/Heck/Annulation Reaction

Article abstract of DOI:10.1002/adsc.201800919

A novel synthesis of functionalized indolines via a Pd-catalyzed tandem decarboxylative amination/Heck/annulation reaction has been developed. This process features operational simplicity, mild conditions, and the use of a readily available and environmentally friendly starting material, namely carboxylic acid. Furthermore, the reaction shows good functional group tolerance and chemical selectivity. (Figure presented.).

Full text of DOI:10.1002/adsc.201800919

Title: Pd-Catalyzed Synthesis of Indolines from Aroyloxycarbamates
through a Tandem Decarboxylative Amination/Heck/Annulation
Reaction
Authors: Zheng Wang, Peihe Li, Hui Fu, qipu Dai, and Changwen Hu
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To be cited as: Adv. Synth. Catal. 10.1002/adsc.201800919
Link to VoR: http://dx.doi.org/10.1002/adsc.201800919

10.1002/adsc.201800919
Advanced Synthesis & Catalysis
FULL PAPER
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Palladium-Catalyzed Synthesis of Indolines from
Aroyloxycarbamates through a Tandem Decarboxylative
Amination/Heck/Annulation Reaction
Zheng Wang,a Peihe Li,a Hui Fu,a Qipu Dai,a* and Changwen Hua*
a Key Laboratory of Cluster Science of Ministry of Education, Beijing Key Laboratory of
Photoelectronic/Electrophotonic, School of Chemistry and Chemical Engineering, Beijing Institute of Technology,
Beijing 100081, China; E-mail: daiqipu@bit.edu.cn; cwhu@bit.edu.cn
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.((Please
delete if not appropriate))
Abstract:
A
novel synthesis of functionalized indolines via
a
Pd-catalyzed tandem decarboxylative
amination/Heck/annulation reaction has been developed. This process features operational simplicity, mild conditions, and
the use of a readily available and environmentally friendly starting material, namely carboxylic acid. Furthermore, the
reaction shows good functional group tolerance and chemical selectivity.
Keywords: Decarboxylation; Amination; Indolines; Palladium
Introduction
The indoline scaffold is ubiquitously present in many
natural bioactive alkaloids and pharmaceutically
active compounds. [1] Because of their broad spectrum
of biological and pharmaceutical properties,[2]
numerous elegant methods have been developed for
the synthesis of indolines in the past decades, such as
the replacement of a leaving group by nitrogen,[3]
[4]
intramolecular cyclization,
radical reactions,[5]
direct C‒H amination,[6] and Heck reaction/cyclization
reactions.[7] Among these methods, constructing
indolines using a tandem Heck coupling /cyclization
reaction between olefins and aryl halides is a very
effective method.[8] Nevertheless, avoiding β-
hydrogen elimination, which leads to the formation of
the Heck-type products and prevents the cyclization, is
the most challenging aspect of this methodology. [ 6f]
To overcome this problem, one of the efficient
approaches is to employ norbornene and 1,3-dienes as
alkene sources because of their unique chemical and
spatial characters.[9,10] Indeed, many reports on the use
of norbornene and 1,3-dienes for the synthesis of
indolines have appeared in the past decades. For
examples, Catellani,[9] Larock,[7a] Lautens[11] and
Saito[12] have successively reported the annulation of
haloanilines with norbornadiene species. This strategy
was further extended by Jiang[6f] through a C-H
Scheme 1. Synthesis of indolines.
activation process. In addition, Larock[7b, 7c] has also
realized a Pd-catalyzed heteroannulation of 1,3-dienes
with nitrogen substituted aryl halides for the synthesis
of
indoline.
Recently,
an
enantioselective
heteroannulation of 1,3-dienes with aryl iodides was
reported by Han[10a]. Extensions of this approach via a
C-H activation pathway were also reported by Booker-
Milburn[10b] and Han.[10c] In most of the
aforementioned methods, anilines were used as
starting materials. Taking into consideration that
carboxylic acids are readily available, are
environmentally friendly, and have great synthetic
potential, herein we introduce an alternative approach
1
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10.1002/adsc.201800919
Advanced Synthesis & Catalysis
Table 1. Optimization of the reaction conditions.[a]
Table 2. Substrate scope.[a]
Entry Catalyst
Ligand Base
Solvent Yield[b](%)
Cs2CO3 toluene 60
Cs2CO3 toluene 52
1
2
3
4
Pd(OAc)2
Pd(TFA)2
Pd2(dba)3
PdCl2
L1
L1
L1
L1
L2
L3
L4
L2
L2
L2
L2
L2
L2
L2
L2
L2
L2
Cs2CO3 toluene 58
Cs2CO3 toluene 64
Cs2CO3 toluene 70
Cs2CO3 toluene 32
Cs2CO3 toluene 58
K2CO3 toluene 23
t-BuOK toluene
DBU
Et3N
5
PdCl2
6
PdCl2
PdCl2
PdCl2
7[c]
8
9
PdCl2
0
0
0
10
11
12
13
PdCl2
PdCl2
PdCl2
toluene
toluene
[a]Reaction conditions: 1 (0.3 mmol), 2 (1.8 mmol), PdCl2
(10 mol%), (t-Bu)3P•BF4 (20 mol%), Cs2CO3 (0.6 mmol)
in 3 ml benzene at 120 °C for 12h under Ar. Yield of
isolated product was shown. Unless otherwise noted, X =
Br.
Cs2CO3 benzene 78(74)[d]
Cs2CO3 xylene 55
Cs2CO3 MeCN 52
Cs2CO3 CHCl3 46
PdCl2
14[e] PdCl2
15[e] PdCl2
[b]N-COOMe was used as the protecting group instead of N-
Boc.
16
17
PdCl2
PdCl2
Cs2CO3 DMF
8
Cs2CO3 benzene 24[f]
[a]Reaction conditions: 1a (0.2 mmol), 2 (1.2 mmol), catalyst
(10 mol%), ligand (20 mol%), base (0.4 mmol) in solvent
(2mL) at 120 °C for 12 h under Ar.
intramolecular decarboxylative amination reaction to
give the 2-halogenaniline intermediate. An ensuing
Heck reaction with the alkenes followed by the
intramolecular cyclization gives the indolines. To the
best of our knowledge, there is no report using this
kind of carboxylic acid derivatives as the substrates for
the synthesis of indolines. This work extends the utility
of the decarboxylative amination reaction, and
provides another practical synthesis of indoline
derivatives.
[b]Unless otherwise noted, the yields were determined by GC
analysis using mesitylene as internal standard.
[c]10 mol% ligand was used.
[d]The yield of the isolated product is shown in parentheses.
[e]The reaction was conducted at 100 °C.
[f]The reaction was carried out from 2-bromobenzoic acid in
situ without separation and purification. Isolated yield.
for
the
synthesis
of
indolines
from
haloaroyloxycarbamates, which can be readily
synthesized from carboxylic acids.[13a]
Results and Discussion
Based on our decarboxylation/amination reaction,[13a]
we successfully achieved the synthesis of 2-
Our
investigations
of
this
Pd-catalyzed
vinylanilines
decarboxylation/Heck
through
a
sequential
from 2-
decarboxylation/annulation reaction were commenced
with aroyloxycarbamate (1a) and norbornadiene (2) as
the model substrates and the reaction conditions were
optimized first. As shown in Table 1, when 1a and 2
were treated with 10 mol% of Pd(OAc)2 and 20 mol%
Ph3P in the presence of 2 equiv of Cs2CO3 in toluene,
the reaction gave indoline 3a in 60% yield (Table 1,
entry 1). Other Pd catalysts such as Pd(TFA)2,
Pd2(dba)3, PdCl2 were also tested (Table 1, entries 2-
4), and the results showed PdCl2 to be the best catalyst
(Table 1, entry 4). Considering the important influence
of ligand, we examined various phosphine ligands
(Table 1, entries 5-7). The results showed that an
electron-rich phosphine ligand, (t-Bu)3P∙BF4, gave the
best performance (Table 1, entry 5). In addition,
reaction
haloaroyloxycarbamates in 2017 (Scheme 1a).[13b]
Although we eventually obtained indole by applying
NIS on the tandem reaction products, no direct
annulation product was obtained. To achieve
annulation product directly remains an elusive and
challenging task. Considering the good activity of
alkenes and their immense potentials in total synthesis,
we introduced norbornadiene and 1,3-diene in our
decarboxylative amination system, and realized a
tandem decarboxylative amination/annulation reaction
for the synthesis of indolines (Scheme 1b). Substrate
1, which can be easily prepared from benzoic acids and
N-protected hydroxylamines in one pot, undergoes an
2
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10.1002/adsc.201800919
Advanced Synthesis & Catalysis
Table 3. Substrate scope.[a]
(Table 2, 3k). When the alkene component was
switched from norbornadiene to norbornene, the
reaction proceeded well (Table 2, 3l). Similarly, when
the protecting group was changed from Boc to Cbz, the
corresponding product was obtained in 65% yield
(Table2, 3m). In addition, when COOMe was used as
the protecting group, the deprotected products 3n and
3o were obtained in 41% and 39% yields, respectively.
We also tried some other alkenes, such as styrene,
cycloocta-1,5-diene,
cyclohexene,
(E)-1,2-
diphenylethene and indole, but no indoline product
was obtained. On the other hand, when indene was
used as the alkene component in this reaction, a
complex reaction mixture was obtained.
Inspired by Larock’s work,[7b, 7c] we next examined
1,3-diene as alkene source in this reaction. The desired
indoline products were obtained and, as expected,
substrates with both electron-donating (Table 3, 3ab,
3ac, and 3af) and electron-withdrawing (Table 3, 3ad,
3ae, and 3ag) groups showed good reactivities and
produced the desired products in 34-56% yields. In
general, substrates with electron-donating group gave
higher yields, for examples, 3ab, 3ac, and 3ag were
obtained in 49%, 38%, and 46% yield respectively. On
a separate note, 1,3-dienes substituted with a
naphthalene (Table 3, 3ah) or a pyridine (Table 3, 3ai)
were well tolerated in this reaction and the
corresponding products were isolated with 47% and
55% yields, respectively.
[a]Reaction conditions: 1b (0.3 mmol), 2 (0.6 mmol, 2 equiv),
Pd(OAc)2 (0.03 mmol, 10 mol%), (o-Tol)3P (0.06 mmol,
20 mol%), Cs2CO3 (0.6 mmol, 2 equiv) in 3 mL toluene
at 120 °C for 12 h under Ar atmosphere. Yield of isolated
product is shown.
Cs2CO3 turned out to be the best base for this reaction,
whereas K2CO3, t-BuOK, DBU, and Et3N were wrose
ones (Table 1, entry 5, entries 9-11). Among the
common solvents screened, the best yield was
obtained in benzene (Table 1, entry 12), whereas
xylene, MeCN, and CHCl3 led to the product 3a in
lower yields (Table1, entries 13-15). When the
reaction was carried out in the polar solvent DMF,
only 8% yield of 3a was obtained (Table 1, entry 16).
With the optimized reaction condition in hand, we
next examined the scope of this method (Table 2). As
is evident from the results in Table 2, a variety of
substrates can be present in different positions of the
substrate 1. In addition, 2-iodo-, 2-bromo-, and 2-
chloro- substituted aroyloxycarbamates could all
participate in this reaction, with the 2-bromo-
substituted aroyloxycarbamate gave the best yield of
3a (74%, Table 2). The reaction could also proceed
well in the presence of several functionalities
including electron-donating groups (Table 2, 3b, 3c,
3d, 3g and 3j) and halogen atoms (Table 2, 3e, 3f, 3h,
and 3i) at different positions around the aromatic rings.
In general, electron-donating group gave higher yields
of the desired indoline products, and among them the
highest yield was obtained for compound 3j (74%
yield). It was worth noting that chloride was an active
substrate and showed good performance in this
reaction, it could also act as a function group in this
reaction with favorable tolerance. This reaction could
also proceed smoothly with naphthalene in 48% yield
Scheme 2. Application of indoline synthesis.
As alkene is a reactive function group, the annulated
indoline product can be transformed to several other
products,[14] such as indole, tricyclic indoline epoxide,
and dihydroxylation products and can even be used as
substrates in total synthesis[15]. To demonstrate the
potential utility of the indoline products, compounds
3
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10.1002/adsc.201800919
Advanced Synthesis & Catalysis
N-Boc hydroxylamine was prepared from hydroxylamine
hydrochloride with (Boc)2O, according to a known
procedure. A suspension of NH2OH·HCl (9.6 g, 0.14 mol,
1.5equiv) and K2CO3 (7.2 g, 0.07 mol, 1.5 equiv) in Et2O
(60 mL) and H2O (2 mL) was stirred for about 1 h at room
temperature with evolution of CO2 gas. A solution of Boc2O
(20.0 g, 92 mmol) in Et2O (40 mL) was then added dropwise
at 0 °C and the suspension was stirred at room temperature
for 12 h. The organic phase was decanted and the solid was
washed with Et2O (30 mL × 2) and the organic layers were
combined and concentrated. Recrystallization with a
cyclohexane/toluene mixture afforded the desired product.
Scheme 3. Proposed reaction pathway.
1b and 3a were employed as the starting materials to
form the diindoline cyclic products 4a and 4b in the
yield of 45% and 21%, respectively.
According to our previous work and mechanistic
study,[13] the proposed reaction pathway is shown in
Scheme 3. Firstly, the intermediate of 6 was obtained
via an intramolecular decarboxylation process. Next,
norbornadiene reacted with 6 via a tandem Heck-type
reaction and nitrogen nucleophilic pathway to form the
cyclization product.[11] In the case of the 1,3-diene
substrate, the reaction went through a similar tandem
Heck/intramolecular Tsuji–Trost pathway.[16]
Synthesis of N-Cbz and N-COOMe hydroxylamines[17]
N-Cbz and N-COOMe hydroxylamines were prepared from
hydroxylamine with the corresponding chloroformates
according to
a
known procedure. Hydroxylamine
Conclusion
hydrochloride (13.9 g, 200 mmol) was added to aqueous
solution of NaOH (1.5 M, 160 mL, 240 mmol). The solution
was cooled to 0°C and the corresponding chloroformate (38
mmol) was added dropwise. Upon the completion of
addition, the mixture was warmed up to room temperature
and stirred for additional 2 h. The reaction was then
acidified with aqueous HCl (6 M) until pH was around 4.5.
Then the mixture was extracted with Et2O (200 mL × 3) and
the combined organic layers were washed with brine and
dried over anhydrous Na2SO4. After removal of the solvent
in vacuum, the carbamate was used directly without further
purification.
In conclusion, we have realized a new tandem
approach for the synthesis of indolines through the
annulation of 2-halo-aroyloxycarbamates with
norbornadiene,
norbornene,
and
1,3-dienes.
Employing arylcarboxylic acids as the starting
materials, we successfully achieved the transformation
to arylamines in situ followed by an annulation with
olefins under mild conditions with high functional
group tolerance. Further elucidation of the detailed
mechanism and development of the related
decarboxylative C-H activation reactions are under
way in our laboratory.
Synthesis of aroyloxycarbamates 1[17]
To a flame-dried round bottom flask (250mL) equipped
with a stir bar, an N-protected hydroxylamine (20 mmol, 1.0
equiv), 2-halobenzoic acid (21 mmol) and anhydrous
CH2Cl2 (80 mL) were added. The flask was cooled to -15 °C.
DCC (4.53 g, 22 mmol, dissolved in 20 mL of anhydrous
CH2Cl2) solution was then added dropwise. The reaction
mixture was stirred at the same temperature for additional
30 min until the N-protected hydroxylamine was fully
consumed (monitored by TLC). The white precipitate
(N,N’-dicyclohexylurea) was removed by filtration and the
filtrate was concentrated in vacuo and dissolved again in
Et2O (30 mL). The solution was cooled to -20 °C for 2 h and
filtered again to remove additional precipitate. The organic
layer was then concentrated in vacuum and the residue was
recrystallized from hexane and EtOAc to afford
corresponding acyloxylcarbamate 1 (65-86% yields).
Experimental Section
General methods.
All commercially available reagents were used without
further purification. All solvents were purified and dried
according to standard methods prior to use. Column
chromatography was performed on silica gel (200-400
mesh). GC-MS data were performed on Agilent 7890A. GC
analyses were performed on a Shimadzu GC-2014 equipped
with a capillary column (HP-5.30 m × 0.25 μm) using a
1
flame ionization detector. H NMR and 13C NMR spectra
were recorded using Bruker 400 MHz NMR or Bruker 700
MHz NMR spectrometer. Chemical shifts were reported in
parts per million (ppm) referenced to the appropriate solvent
peak or 0.0 ppm for tetramethylsilane and the center of a
triplet at 77.0 ppm of chloroform-d. The following
abbreviations were used to designate chemical shift
multiplicities: s = singlet, d = doublet, t = triplet, q = quartet,
sep = septet, dd = doublet of doublet, td = triplet of doublet,
br = broad, m = multiplet. The FTIR spectra was recorded
from KBr pellets in the range from 4000 to 400 cm−1 on a
Nicolet 170 SXFT/IR spectrometer. Melting points were
determined using an X-4 apparatus and were uncorrected.
Synthesis of 1,3-dienes[18]
To a 250 mL oven dried round bottom flask was added 4.6
g of allyltriphenylphosphonium bromide (12 mmol, 1.2
equiv). The flask was purged with N2 and 100 mL of THF
o
was added. The suspension was cooled to 0 C and 7.5 mL
of a n-BuLi solution (1.6 M solution in hexanes, 12 mmol,
1.2 equiv) was added dropwise by syringe. The reaction
mixture was stirred for 30 min followed by dropwise
addition of aldehyde (10 mmol, 1.0 equiv) in 15 mL THF.
Synthesis of N-Boc hydroxylamine[17]
4
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10.1002/adsc.201800919
Advanced Synthesis & Catalysis
After 1 h, the reaction mixture was allowed to slowly warm
to r.t. and stirred for 3-5 h (monitored by TLC). A saturated
solution of NH4Cl (50 ml) was added followed by extraction
with Et2O (2×50 ml). The combined organic phases was
washed with brine, dried over Na2SO4 and the solvent was
removed under reduced pressure. The product was then
purified by flash column chromatography (hexanes:EtOAc
= 50:1) to afford the desired product (62-85% yields).
(63 mg, 74%); Rf = 0.25 (hexane:EtOAc = 100:1); 1H NMR
(400 MHz, CDCl3) δ 7.84 (br, 0.6H), 7.43 (br, 0.4H), 7.23–
7.12 (m, 2H), 6.93 (t, J = 7.2 Hz, 1H), 6.33 (s, 1H), 6.12 (s,
1H), 4.29–4.21 (m, 1H), 3.39–3.22 (m, 2H), 2.92 (s, 1H),
1.59 (s, 9H), 1.42 (s, 2H); 13C NMR (101 MHz, CDCl3) δ
152.6, 152.3, 146.3, 145.3, 139.8, 139.3, 136.0, 135.5, 132.5,
131.7, 127.7, 124.3, 123.8, 122.2, 114.7, 81.6, 80.4, 66.0,
48.4, 48.1, 47.6, 47.4, 46.9, 46.3, 42.0, 28.5.
tert-butyl
8-methyl-1,4,4a,9a-tetrahydro-9H-1,4-
methanocarbazole-9-carboxylate (3b) White solid (54 mg,
61%); mp: 75–77 °C; Rf = 0.25 (hexane:EtOAc = 100:1); IR
Procedures for the preparation of products
1
(film) 2946, 1715, 1453, 1371, 1032 cm-1; H NMR (400
To a flame-dried and Ar-purged Schlenk tube (10 mL) were
added 2-halogen aroyloxycarbamates (0.3 mmol, 1.0 equiv),
Pd catalyst (0.03 mmol, 0.1 equiv), phosphine ligand (0.06
mmol, 0.2 equiv), Cs2CO3 (0.6 mmol, 2.0 equiv) and a stir
bar. The Schlenk tube was then evacuated and filled with
argon. This cycle was repeated three times and followed by
addition of norbornadiene (1.8 mmol, 6 equiv) or 1,3-diene
(0.6 mmol, 2 equiv) in solvent (3 mL) via syringe. The
reaction was allowed to heat at 120 °C for 12 h. Then the
reaction mixture was filtrated and purified carefully by flash
chromatography (hexanes and EtOAc) to give the desired
product 3.
MHz, CDCl3) δ 7.00–6.94 (m, 3H), 6.30–6.28 (m, 1H),
6.15–6.13 (m, 1H), 4.19 (d, J = 7.5 Hz, 1H), 3.46 (d, J = 7.5
Hz, 1H), 3.13 (s, 1H), 2.80 (s, 1H), 2.28 (s, 3H), 1.55 (s, 9H),
1.33 (d, J = 9.2 Hz, 1H), 1.16 (d, J = 9.2 Hz, 1H); 13C NMR
(176 MHz, CDCl3) δ 154.1, 144.2, 139.2, 135.9, 134.2,
130.6, 126.6, 123.7, 121.0, 80.5, 67.4, 48.9, 48.2, 47.4, 42.0,
28.4, 20.9. HRMS (ESI-TOF) m/z: Calcd for C19H23NO2 [M
+ H]+ 298.1802; found 298.1810.
tert-butyl
7-methoxy-1,4,4a,9a-tetrahydro-9H-1,4-
methanocarbazole-9-carboxylate (3c). White solid (64 mg,
68%); mp: 88–91 °C; Rf = 0.2 (hexane:EtOAc = 100:1); IR
1
(film) 2966, 2360, 1652, 1385, 1019 cm-1; H NMR (400
MHz, CDCl3) δ 7.52 (br, 0.6H), 7.08 (br, 0.4H), 6.99 (d, J =
7.6 Hz, 1H), 6.49 (dd, J = 8.0 Hz, 2.0 Hz, 1H), 6.30 (s, 1H),
6.09 (s, 1H), 4.29–4.21 (m, 1H), 3.79 (s, 3H), 3.30–3.19 (m,
2H), 2.86 (s, 1H), 1.58 (s, 9H), 1.41 (s, 2H); 13C NMR (176
MHz, CDCl3) δ 159.8, 159.6, 152.6, 152.4, 147.4, 146.4,
139.8, 139.3, 135.8, 135.3, 124.8, 124.5, 124.1, 123.8, 108.9,
107.7, 101.5, 100.4, 81.6, 80.4, 67.0, 55.5, 48.5, 48.4, 48.1,
47.3, 46.9, 46.2, 42.0, 28.5. HRMS (ESI-TOF) m/z: Calcd
for C19H23NO3 [M + H]+ 314.1751; found 314.1751.
Procedures for the Preparation of Products from 2-
bromobenzoic acid in situ
To a solution of 2-bromobenzoic acid (0.4 mmol, 80mg) in
Anhydrous DCM (3 mL) in a flame-dried Schlenk tube (10
mL), CDI (N,N'-Carbonyldiimidazole) (0.4 mmol, 65 mg)
were added at 0 °C. After 30 minutes, the mixture was
warmed up to room temperature. Then N-Boc
hydroxylamine (0.4 mmol, 53 mg) was added and the
reaction was stirred at r.t. for 2 h. After that, the solvent was
removed in vacuo and PdCl2 (0.04 mmol, 7 mg), Tri-tert-
butylphosphine tetrafluoroborate (0.08 mmol, 23 mg),
Cs2CO3 (0.8 mmol, 260 mg) were added. The Schlenk tube
was evacuated and filled with argon. This cycle was
repeated three times and followed by addition of
norbornadiene (2.4 mmol, 220 mg) in benzene (3 mL) via
syringe. The reaction was allowed to heat at 120 °C for 12
h. Then the reaction mixture was filtrated and purified
carefully by flash chromatography (hexanes and EtOAc) to
give the desired product 3 in 24% yield.
tert-butyl
7-methyl-1,4,4a,9a-tetrahydro-9H-1,4-
methanocarbazole-9-carboxylate (3d). White solid (53
mg, 60%); mp: 117–119 °C; Rf = 0.25 (hexane:EtOAc =
1
100:1); IR (film) 2975, 1704, 1498, 1383, 1141 cm-1; H
NMR (400 MHz, CDCl3) δ 7.99 (br, 0.3H), 7.70 (br, 0.7H),
7.00 (d, J = 7.6 Hz, 1H), 6.75 (d, J = 7.6 Hz, 1H), 6.32 (s,
1H), 6.10 (s, 1H), 4.29–4.18 (m, 1H), 3.34–3.20 (m, 2H),
2.88 (s, 1H), 2.32 (s, 3H), 1.58 (s, 9H), 1.41 (s, 2H); 13C
NMR (176 MHz, CDCl3) δ 152.8, 152.5, 146.4, 145.5,
139.8, 139.3, 137.8, 137.3, 136.0, 135.4, 129.7, 128.9, 123.9,
123.5, 123.0, 122.8, 115.8, 115.4, 81.5, 80.4, 66.5, 48.4,
48.1, 47.3, 46.5, 42.0, 28.5, 28.3, 21.9, 21.7. HRMS (ESI-
TOF) m/z: Calcd for C19H23NO2 [M + H]+ 298.1802; found
298.1805.
Preparation of 4a and 4b.
To a flame-dried and Ar-purged Schlenk tube (10 mL) were
added 3a (0.3 mmol, 1 equiv), 1a (0.6 mmol, 2 equiv), PdCl2
tert-butyl
7-fluoro-1,4,4a,9a-tetrahydro-9H-1,4-
methanocarbazole-9-carboxylate (3e).[11] White solid (52
mg, 58%); mp: 89–92 °C; Rf = 0.2 (hexane:EtOAc = 100:1);
1H NMR (400 MHz, CDCl3) δ 7.59 (d, J = 9.8 Hz, 0.6H),
7.13 (br, 0.4H), 7.03–7.00 (m, 1H), 6.61 (t, J = 8.4 Hz, 1H),
6.31 (s, 1H), 6.11 (s, 1H), 4.33–4.23 (m, 1H), 3.33–3.21 (m,
2H), 2.88 (s, 1H), 1.57 (d, J = 2.4 Hz, 9H), 1.42 (t, J = 11.5
Hz, 2H); 13C NMR (176 MHz, CDCl3) δ 163.4, 162.1, 152.2,
147.6, 146.6, 139.7, 139.2, 136.0, 135.4, 128.0, 127.2, 124.7,
124.2, 124.2, 108.7, 108.6, 108.5, 103.0, 102.9, 82.2, 80.8,
67.1, 48.5, 48.4, 48.1, 47.3, 47.0, 46.2, 42.0, 28.4.
(0.03 mmol,
0.1
equiv),
tri-tert-butylphosphine
tetrafluoroborate (0.06 mmol, 0.2 equiv), Cs2CO3 (0.6 mmol,
2.0 equiv) and a stir bar. The Schlenk tube was then
evacuated and filled with argon. This cycle was repeated
three times and followed by addition of toluene (3 mL) via
syringe. The reaction was allowed to heat at 120 °C for 24
h. Then the reaction mixture was filtrated and purified
carefully by flash chromatography (hexane:EtOAc = 50:1)
to give the desired product 4a and 4b. If the product was a
yellow solid or was a yellow oil, it was recrystallized from
EtOAc and hexane to give a white solid.
tert-butyl
7-chloro-1,4,4a,9a-tetrahydro-9H-1,4-
methanocarbazole-9-carboxylate (3f). White solid (57 mg,
60%); mp: 112–115 °C; Rf = 0.25 (hexane:EtOAc = 100:1);
Spectroscopic Data of Compounds
IR (film) 2887, 1703, 1481, 1379, 1164, 1038 cm-1; H
1
tert-butyl
1,4,4a,9a-tetrahydro-9H-1,4-
methanocarbazole-9-carboxylate (3a).[11] Colorless oil
NMR (700 MHz, CDCl3) δ 7.88 (br, 0.65H), 7.41 (br,
5
This article is protected by copyright. All rights reserved.

10.1002/adsc.201800919
Advanced Synthesis & Catalysis
0.35H), 7.01 (d, J = 7.0 Hz, 1H), 6.90 (dd, J = 7.0, 1.9 Hz,
1H), 6.32 (s, 1H), 6.12 (d, J = 27.1 Hz, 2H), 4.32–4.21 (m,
1H), 3.33–3.21 (m, 2H), 2.89 (s, 1H), 1.59 (d, J = 31.8 Hz,
9H), 1.44 (d, J = 9 Hz, 1H), 1.40–1.39 (m, 1H); 13C NMR
(176 MHz, CDCl3) δ 152.2, 147.3, 146.4, 139.7, 139.2,
tert-butyl
1,2,3,4,4a,9a-hexahydro-9H-1,4-
methanocarbazole-9-carboxylate (3l).[14a] Yellow solid
(38 mg, 44%); mp: 61–63 °C; Rf = 0.25 (hexane:EtOAc =
100:1); 1H NMR (400 MHz, CDCl3) δ 7.80 (br, 0.65H), 7.40
(br, 0.35H), 7.13–7.08 (m, 2H), 6.91 (t, J = 8 Hz, 1H), 4.17–
136.0, 135.5, 133.4, 133.1, 131.0, 130.2, 124.9, 124.5, 122.2, 4.09 (m, 1H), 3.23 (d, J = 8 Hz, 1H), 2.69–2.58 (m, 1H),
122.1, 115.3, 115.1, 82.2, 80.9, 66.8, 48.3, 48.1, 47.2, 46.5,
45.9, 42.0, 28.4. HRMS (ESI-TOF) m/z: Calcd for
C18H20ClNO2 [M + Na]+ 340.1075; found 340.1082.
2.30 (s, 1H), 1.63–1.55 (m, 11H) 1.36 (d, J = 8 Hz, 1H),
1.30–1.26 (m, 3H), 1.07 (d, J = 10 Hz, 1H); 13C NMR (101
MHz, CDCl3) δ 152.5, 144.6, 143.9, 134.4, 133.5, 127.5,
124.7, 124.2, 122.2, 114.2, 81.4, 80.2, 67.4, 49.9, 49.1, 43.2,
42.2, 41.4, 32.0, 28.5, 28.2, 25.5.
tert-butyl
6-methyl-1,4,4a,9a-tetrahydro-9H-1,4-
methanocarbazole-9-carboxylate (3g).[11] Colorless oil
(58 mg, 65%); Rf = 0.25 (hexane:EtOAc = 100:1); 1H NMR
(400 MHz, CDCl3) δ 7.69 (br, 0.6H), 7.30 (br, 0.4H), 6.99–
6.93 (m, 2H), 6.31 (s, 1H), 6.11 (s, 1H), 4.27–4.18 (m, 1H),
3.34–3.20 (m, 2H), 2.89 (s, 1H), 2.28 (s, 3H), 1.57 (s, 9H),
1.41 (s, 2H); 13C NMR (176 MHz, CDCl3) δ 152.8, 152.4,
benzyl
1,2,3,4,4a,9a-hexahydro-9H-1,4-
methanocarbazole-9-carboxylate (3m). Yellow oil (62 mg,
65%); Rf = 0.3 (hexane:EtOAc = 40:1); IR (film) 2949, 1701,
1453, 1403, 1032 cm-1; 1H NMR (400 MHz, CDCl3) δ 7.86
(d, J = 7.6 Hz, 0.65H), 7.42–7.33 (m, 5.35H), 7.18–7.11 (m,
144.0, 143.1, 139.8, 139.3, 136.0, 135.5, 132.6, 131.8, 131.7, 2H), 6.95 (t, J = 6.4 Hz, 1H), 5.29 (s, 2H), 4.22 (d, J = 7.6
128.3, 128.1, 125.0, 124.6, 114.6, 114.5, 81.4, 80.2, 66.2,
48.5, 48.4, 48.1, 47.6, 47.4, 46.9, 42.1, 28.5, 20.9, 20.8.
Hz, 1H), 3.27 (d, J = 8.0 Hz, 1H), 2.69 (d, J = 8.0 Hz, 1H),
2.32 (s, 1H), 1.62–1,59 (m, 2H), 1.41–1.28 (m, 3H), 1.08 (d,
J = 11.6 Hz, 1H); 13C NMR (101 MHz, CDCl3) δ 153.0,
144.3, 136.6, 133.6, 128.6, 128.3, 128.0, 127.7, 127.7, 124.8,
124.3, 122.8, 114.4, 67.7, 67.2, 66.7, 50.1, 49.3, 43.2, 42.2,
32.0, 28.1, 25.5. HRMS (ESI-TOF) Calcd for C21H21NO2
m/z: [M + Na]+ 320.1645; found 320.1637.
tert-butyl
6-fluoro-1,4,4a,9a-tetrahydro-9H-1,4-
methanocarbazole-9-carboxylate (3h).[11] Yellow soild
(52 mg, 58%); mp: 58–60°C; Rf = 0.25 (hexane:EtOAc =
100:1); 1H NMR (400 MHz, CDCl3) δ 7.77 (br, 0.6H), 7.33
(br, 0.4H), 6.82 (d, J = 7.0 Hz, 2H), 6.32 (s, 1H), 6.12 (s,
1H), 4.32–4.21 (m, 1H), 3.36–3.22 (m, 2H), 2.91 (s, 1H),
1.57 (s, 9H), 1.43 (t, J = 11.6 Hz, 2H). 13C NMR (176 MHz,
CDCl3) δ 159.4, 158.3, 152.5, 152.3, 142.3, 141.4, 139.6,
4,4a,9,9a-tetrahydro-1H-1,4-methanocarbazole (3n)[15]
.
Brown solid (22.5 mg, 41%); mp: 62–65 °C; Rf = 0.3
(hexane:EtOAc = 20:1); 1H NMR (400 MHz, CDCl3) δ 7.05
139.1, 136.2, 135.6, 134.3, 133.5, 115.4, 115.4, 114.0, 113.9, (d, J = 7.3 Hz, 1H), 6.99 (t, J = 7.6 Hz, 1H), 6.66 (t, J = 7.3
113.7, 111.5, 111.4, 111.1, 111.0, 81.7, 80.5, 66.5, 48.3,
48.2, 47.5, 47.4, 46.8, 46.4, 42.0, 28.5.
Hz, 1H), 6.52 (d, J = 7.8 Hz, 1H), 6.28 (dd, J = 5.6, 3.0 Hz,
1H), 6.04 (dd, J = 5.6, 3.0 Hz, 1H), 3.93 (d, J = 8.1 Hz, 1H),
3.79 (br, 1H), 3.44 (d, J = 8.0 Hz, 1H), 2.90 (s, 1H), 2.84 (s,
tert-butyl
6-chloro-1,4,4a,9a-tetrahydro-9H-1,4-
1H), 1.63 (d, J = 9.0 Hz, 1H), 1.48 (d, J = 9.0 Hz, 1H); 13
C
methanocarbazole-9-carboxylate (3i).[11] Colorless oil (58
NMR (101 MHz, CDCl3) δ 154.2, 139.6, 135.4, 129.9,
127.7, 124.2, 118.2, 109.0, 64.1, 50.5, 50.4, 48.4, 42.3.
1
mg, 61%); Rf = 0.25 (hexane:EtOAc = 100:1); H NMR
(400 MHz, CDCl3) δ 7.76 (d, J = 7.3 Hz, 0.6H), 7.31 (br,
0.4H), 7.11–7.08 (m, 2H), 6.31 (s, 1H), 6.11 (s, 1H), 4.29–
4.21 (m, 1H), 3.35–3.21 (m, 2H), 2.91 (s, 1H), 1.57 (s, 9H),
1.45–1.40 (m, 2H); 13C NMR (176 MHz, CDCl3) δ 152.3,
2,3,4,4a,9,9a-hexahydro-1H-1,4-methanocarbazole
(3o).[14a] White solid (22 mg, 39%); mp: 91–92 °C; Rf = 0.3
(hexane:EtOAc = 20:1); 1H NMR (400 MHz, CDCl3) δ 7.03
152.2, 144.9, 144.0, 139.6, 139.1, 136.1, 135.5, 134.3, 133.5, (d, J = 7.2 Hz, 1H), 6.98 (t, J = 7.6 Hz, 1H), 6.65 (t, J = 8
127.6, 127.5, 127.0, 126.4, 124.4, 124.0, 115.7, 81.9, 80.7,
66.4, 48.3, 48.1, 47.4, 46.7, 46.2, 42.0, 28.4.
Hz, 1H), 6.51 (d, J = 8 Hz, 1H), 3.77 (d, J = 8 Hz, 1H), 3.61
(br, 1H), 3.28 (d, J = 8 Hz, 1H), 2.30 (s, 1H), 2.20 (d, J = 4
Hz, 1H), 1.62–1.49 (m, 3H), 1.39–1.34 (m, 1H), 1.24–1.14
(m, 2H); 13C NMR (400 MHz, CDCl3) δ 152.5, 131.9, 127.4,
124.5, 118.0, 108.3, 65.3, 52.4, 44.3, 43.2, 32.3, 28.6, 25.3.
tert-butyl
5-methyl-1,4,4a,9a-tetrahydro-9H-1,4-
methanocarbazole-9-carboxylate (3j).[11] White solid (66
mg, 74%); mp: 92–95 °C; Rf = 0.25 (hexane:EtOAc =
100:1); 1H NMR (400 MHz, CDCl3) δ 7.70 (br, 0.6H), 7.34
(br, 0.4H), 7.08–7.05 (m, 1H), 6.75 (d, J = 7.5 Hz, 1H), 6.33
(s, 1H), 6.14 (s, 1H), 4.29–4.22 (m, 1H), 3.36–3.24 (m, 2H),
3.03 (s, 1H), 2.32 (s, 3H), 1.58 (s, 9H), 1.43 (s, 2H); 13C
NMR (101 MHz, CDCl3) δ 139.9, 135.5, 127.9, 123.7,
112.3, 80.3, 66.0, 48.1, 47.1, 46.1, 42.2, 28.5, 18.4.
tert-butyl (E)-2-styrylindoline-1-carboxylate (3aa).
Colorless oil (54 mg, 56%); Rf = 0.25 (hexane:EtOAc =
1
50:1); IR (film) 2949, 1756, 1380, 1244, 1032 cm-1; H
NMR (400 MHz, CDCl3) δ 7.78 (br, 1H), 7.36–7.33 (m, 2H),
7.31–7.27 (m, 2H), 7.24–7.22 (m, 1H), 7.19 (d, J = 8.0 Hz,
1H), 7.15 (d, J = 7.2 Hz, 1H), 6.96 (td, J = 7.2, 0.9 Hz, 1H),
6.52 (d, J = 15.8 Hz, 1H), 6.18 (dd, J = 15.8, 7.7 Hz, 1H),
5.03 (br, 1H), 3.49 (dd, J = 16.2, 10.1 Hz, 1H), 2.88 (dd, J
= 16.2, 2.6 Hz, 2H), 1.52 (s, 9H); 13C NMR (101 MHz,
CDCl3) δ 152.4, 136.7, 130.5, 129.2, 128.6, 127.6, 127.6,
126.4, 124.9, 122.5, 115.2, 80.9, 61.2, 35.0, 28.4. HRMS
(ESI-TOF) m/z: Calcd for C21H23NO2 [M + Na]+ 344.1621;
found 344.1627.
tert-butyl
7a,8,11,11a-tetrahydro-7H-8,11-
methanobenzo[c]carbazole-7-carboxylate (3k). Yellow
solid (48 mg, 48%); mp: 104–106 °C; Rf = 0.3
(hexane:EtOAc = 50:1); IR (film) 2943, 2521, 2041, 1698,
1
1405, 1032 cm-1; H NMR (400 MHz, CDCl3) δ 8.20 (s,
0.6H), 7.85–7.79 (m, 2.4H), 7.71 (d, J = 8.5 Hz, 1H), 7.48
(t, J = 7.5 Hz, 1H), 7.34 (t, J = 7.5 Hz, 1H), 6.45 (d, J = 2.3
Hz, 1H), 6.18 (s, 1H), 4.67–4.40 (m, 1H), 3.80 (d, J = 8.0
Hz, 1H), 3.42–3.29 (m, 2H), 1.61 (s, 9H), 1.45–1.40 (m,
2H); 13C NMR (101 MHz, CDCl3) δ 152.7, 143.9, 140.2,
tert-butyl
(E)-2-(4-methoxystyryl)indoline-1-
carboxylate (3ab). Colorless oil (52 mg, 49%); Rf = 0.2
(hexane:EtOAc = 50:1); IR (film) 2943, 1754, 1450, 1247,
139.6, 135.8, 135.3, 130.3, 129.8, 128.6, 126.3, 123.6, 122.9, 1027 cm-1; 1H NMR (400 MHz, CDCl3) δ 7.78 (br, 1H), 7.27
115.9, 80.6, 66.8, 48.6, 47.1, 46.7, 42.4, 28.6; HRMS (ESI-
TOF) m/z: Calcd for C22H23NO2 [M + H]+ 334.1802; found
334.1813.
(d, J = 8.0 Hz, 2H), 7.21–7.14 (m, 2H), 6.96 (t, J = 7.3 Hz,
1H), 6.83 (d, J = 7.7 Hz, 2H), 6.47 (d, J = 15.7 Hz, 1H), 6.04
(dd, J = 15.7, 7.7 Hz, 1H), 5.00 (s, 1H), 3.79 (s, 3H), 3.48
6
This article is protected by copyright. All rights reserved.

10.1002/adsc.201800919
Advanced Synthesis & Catalysis
(dd, J = 16.0, 10.1 Hz, 1H), 2.87 (d, J = 16.1 Hz, 1H), 1.52
(s, 9H); 13C NMR (101 MHz, CDCl3) δ 159.2, 152.5, 142.2,
132.3, 129.5, 128.0, 127.8, 125.0, 122.7, 122.2, 121.0, 115.3,
60.7, 34.8, 28.5; HRMS (ESI-TOF) m/z: Calcd for
130.0, 129.8, 129.4, 127.6, 127.5, 127.0, 124.9, 122.4, 115.2, C21H22N2O4 [M + Na]+ 389.1472; found 389.1482.
114.0, 80.8, 61.4, 55.3, 35.1, 28.5. HRMS (ESI-TOF) m/z:
tert-butyl
(E)-2-(2-(naphthalen-2-yl)vinyl)indoline-1-
Calcd for C22H26NO3 [M + H]+ 352.1907; found 352.1908.
carboxylate (3ah). Colorless oil (52.4 mg, 47%); Rf = 0.2
tert-butyl
(E)-2-(4-(dimethylamino)styryl)indoline-1-
(hexane:EtOAc = 50:1); IR (film) 2993, 1770, 1482, 1385,
1
carboxylate (3ac). Yellow oil (41.5 mg, 38%); Rf = 0.2
1246, 1057, 913, 744 cm-1; H NMR (400 MHz, CDCl3) δ
(hexane:EtOAc = 20:1); IR (film) 2947, 1675, 1483, 1452,
7.79–7.75 (m, 4H), 7.70 (s, 1H), 7.54 (d, J = 8.5 Hz, 1H),
7.47–7.41 (m, 2H), 7.23 (t, J = 7.7 Hz, 1H), 7.18 (d, J = 7.3
Hz, 1H), 6.98 (t, J = 7.3 Hz, 1H), 6.69 (d, J = 15.7 Hz, 1H),
6.31 (dd, J = 15.7, 7.6 Hz, 1H), 5.09 (s, 1H), 3.53 (dd, J =
16.1, 10.1 Hz, 1H), 2.93 (d, J = 16.2 Hz, 1H), 1.53 (s, 9H);
13C NMR (101 MHz, CDCl3) δ 152.4, 134.1, 133.6, 133.0,
130.6, 129.6, 129.0, 128.2, 127.9, 127.7, 127.6, 126.4, 126.3,
125.9, 124.9, 123.6, 122.5, 115.2, 80.9, 61.3, 35.0, 28.5;
HRMS (ESI-TOF) m/z: Calcd for C25H25NO2 [M + H]+
372.1958; found 372.1970.
1
1389, 1032 cm-1; H NMR (400 MHz, CDCl3) δ 7.81 (br,
1H), 7.28 (s, 1H), 7.24–7.16 (m, 3H), 6.97 (t, J = 7.6 Hz,
1H), 6.67 (d, J = 7.6 Hz, 2H), 6.46 (d, J = 15.6 Hz, 1H), 5.99
(dd, J = 15.6, 8 Hz, 1H), 5.05–4.95 (m, 1H), 3.49 (dd, J =
16, 10 Hz, 1H), 2.97 (s, 6H), 2.89 (d, J = 14.8 Hz, 1H), 1.54
(s, 9H); 13C NMR (101 MHz, CDCl3) δ 152.5, 150.1, 130.6,
127.5, 127.4, 125.1, 124.9, 124.8, 122.3, 115.3, 112.4, 80.7,
61.6, 40.5, 35.2, 28.5. HRMS (ESI-TOF) m/z: Calcd for
C23H29N2O2 [M + H]+ 365.2224; found 365.2218.
tert-butyl (E)-2-(4-fluorostyryl)indoline-1-carboxylate
(3ad). Colorless oil (44 mg, 43%); Rf = 0.25 (hexane:EtOAc
tert-butyl
(E)-2-(2-(pyridin-2-yl)vinyl)indoline-1-
carboxylate (3ai). Colorless oil (53 mg, 55%); Rf = 0.3
(hexane:EtOAc = 10:1); IR (film) 2993, 1770, 1384, 1246,
1
= 50:1); IR (film) 2949, 1677, 1453, 1391, 1032 cm-1; H
NMR (400 MHz, CDCl3) δ 7.77 (br, 1H), 7.31–7.28 (m, 2H), 1059, 913, 748 cm-1; 1H NMR (400 MHz, CDCl3) δ 8.52 (d,
7.20 (t, J = 7.8 Hz, 1H), 7.15 (d, J = 7.3 Hz, 1H), 6.99–6.96
(m, 3H), 6.48 (d, J = 15.7 Hz, 1H), 6.09 (dd, J = 15.8, 7.6
Hz, 1H), 5.01 (br, 1H), 3.48 (dd, J = 16.1, 10.1 Hz, 1H), 2.87
(d, J = 16.1 Hz, 1H), 1.52 (s, 9H); 13C NMR (101 MHz,
CDCl3) δ 163.6, 161.1, 152.4, 132.8, 129.3, 129.0, 128.0,
127.9, 127.6, 124.9, 122.5, 115.6, 115.4, 115.2, 80.9, 61.1,
35.0, 28.4; HRMS (ESI-TOF) m/z: Calcd for C21H22FNO2
[M + Na]+ 362.1527; found 362.1543.
J = 4.4 Hz, 4H), 7.78 (br, 1H), 7.59 (t, J = 7.6 Hz, 1H), 7.23
(d, J = 7 Hz, 1H), 7.18 (t, J = 7.8 Hz, 1H), 7.14–7.09 (m,
2H), 6.94 (t, J = 7.4 Hz, 1H), 6.70 (dd, J = 15.6, 7.2 Hz, 1H),
6.58 (d, J = 15.6 Hz, 1H), 5.09 (br, 1H), 3.50 (dd, J = 16.2,
10.2 Hz, 1H), 2.91 (d, J = 16 Hz, 1H), 1.52 (s, 9H); 13C NMR
(101 MHz, CDCl3) δ 155.1, 152.3, 149.5, 136.4, 133.6,
129.8, 127.5, 124.9, 122.5, 122.2, 121.7, 115.2, 81.0, 60.7,
34.8, 28.4; HRMS (ESI-TOF) m/z: Calcd for C20H22N2O2
[M + H]+ 323.1754; found 323.1755.
tert-butyl (E)-2-(4-chlorostyryl)indoline-1-carboxylate
(3ae). Colorless oil (47 mg, 44%); Rf = 0.25 (hexane:EtOAc
di-tert-butyl
5a,6,6a,11b,12,12a-hexahydro-6,12-
1
= 50:1); IR (film) 2946, 1662, 1389, 1453, 1032 cm-1; H
methanoindolo[2,3-b]carbazole-5,7-dicarboxylate (4a)
NMR (400 MHz, CDCl3) δ 7.78 (br, 1H), 7.31–7.26 (m, 4H), White solid (64 mg, 45%); mp: 206-209 °C; Rf
=
7.20 (t, J = 7.8 Hz, 1H), 7.16 (d, J = 7.3 Hz, 1H), 6.97 (t, J
= 7.4 Hz, 1H), 6.47 (d, J = 15.7 Hz, 1H), 6.16 (dd, J = 15.7,
7.6 Hz, 1H), 5.02 (br, 1H), 3.49 (dd, J = 16.1, 10.1 Hz, 1H),
2.87 (d, J = 16.1 Hz, 1H), 1.52 (s, 9H); 13C NMR (101 MHz,
CDCl3) δ 152.4, 135.2, 133.2, 129.9, 129.2, 128.7, 127.6,
124.9, 122.5, 115.2, 81.0, 61.1, 34.9, 28.4; HRMS (ESI-
TOF) m/z: Calcd for C21H22ClNO2 [M + Na]+ 378.1231;
found 378.1224.
(hexane:EtOAc = 10:1); IR (film) 2971, 2928, 1697, 1485,
1
1390, 1284, 1141, 1046, 752 cm-1; H NMR (400MHz,
CDCl3) δ 7.83 (s, 1H), 7.41 (s, 1H), 7.15–7.12 (m, 4H), 6.92
(t, J = 7.2 Hz, 2H), 4.33 (s, 2H), 3.49 (d, J = 8Hz, 2H), 3.14
(s, 1H), 2.43 (s, 1H), 1.61 (s, 18H), 1.20 (s, 2H); 13C NMR
(176 MHz, CDCl3) δ 152.2, 144.9, 144.2, 132.8, 132.1,
127.9, 124.6, 124.2, 122.3, 114.3, 81.5, 81.0, 64.2, 63.9,
49.7, 48.9, 48.2, 47.7, 28.4, 26.1. HRMS (APCI-TOF) m/z:
Calcd for C29H34N2O4 [M + NH4]+ 492.2857; found
492.2852.
tert-butyl (E)-2-(3-methylstyryl)indoline-1-carboxylate
(3af). Colorless oil (46 mg, 46%); Rf = 0.25 (hexane:EtOAc
= 50:1); IR (film) 2979, 1701, 1483, 1387, 1246, 1163, 1032,
750 cm-1; 1H NMR (400 MHz, CDCl3) δ 7.79 (br, 1H), 7.21
(d, J = 7.4 Hz, 1H), 7.18–7.13 (m, 4H), 7.04 (d, J = 7.2 Hz,
1H), 6.96 (t, J = 7.4 Hz, 1H), 6.49 (d, J = 15.7 Hz, 1H), 6.16
(dd, J = 15.7, 7.7 Hz, 1H), 5.02 (br, 1H), 3.49 (dd, J = 16.1,
10.0 Hz, 1H), 2.87 (d, J = 16.1 Hz, 1H), 2.32 (s, 3H), 1.52
(s, 9H); 13C NMR (101 MHz, CDCl3) δ 152.4, 138.1, 136.6,
di-tert-butyl
5a,6,6a,11a,12,12a-hexahydro-6,12-
methanoindolo[3,2-b]carbazole-5,11-dicarboxylate (4b).
White solid (30 mg, 21%); mp: 213-216 °C; Rf = 0.2
(hexane:EtOAc = 10:1); IR (film) 2974, 2922, 1703, 1483,
1391, 1138, 1042, 750 cm-1; 1H NMR (400 MHz, CDCl3) δ
7.82 (s, 1H), 7.41 (s, 1H), 7.23–7.07 (m, 4H), 6.97–6.95 (m,
2H), 4.35 (d, J = 36.0 Hz, 2H), 3.42 (d, J = 25.4 Hz, 2H),
130.5, 129.0, 128.4, 128.4, 127.5, 127.0, 124.8, 123.6, 122.4, 2.80 (d, J = 45.3 Hz, 2H), 1.61 (s, 18H), 1.22 (s, 2H). 13C
115.1, 80.8, 61.2, 35.0, 28.4, 21.3. HRMS (ESI-TOF) m/z:
NMR (176 MHz, CDCl3) δ 152.6, 152.0, 144.8, 143.9,
132.4, 131.5, 128.1, 127.9, 124.6, 124.1, 122.6, 114.4, 114.3,
81.9, 80.6, 66.2, 49.1, 48.0, 46.6, 45.8, 28.5, 26.0. HRMS
(ESI-TOF) m/z: Calcd for C29H34N2O4 [M + Na]+ 497.2411;
found 497.2410.
Calcd for C22H25NO2 [M + Na]+ 358.1778; found 358.1787.
tert-butyl
(E)-2-(3-nitrostyryl)indoline-1-carboxylate
(3ag). Colorless oil (37 mg, 34%); Rf = 0.25 (hexane:EtOAc
1
= 50:1); IR (film) 2946, 1662, 1453, 1409, 1032 cm-1; H
NMR (400 MHz, CDCl3) δ 8.19 (s, 1H), 8.07 (d, J = 8.1 Hz,
1H), 7.82–7.71 (m, 1H), 7.63 (d, J = 7.6 Hz, 1H), 7.46 (t, J
= 7.8 Hz, 1H), 7.22 (t, J = 7.8 Hz, 1H), 7.17 (d, J = 7.4 Hz,
1H), 6.98 (t, J = 7.2 Hz, 1H), 6.57 (d, J = 15.8 Hz, 1H), 6.34
(dd, J = 15.8, 7.3 Hz, 1H), 5.08 (br, 1H), 3.53 (dd, J = 16.0,
10.2 Hz, 1H), 2.89 (d, J = 16.2 Hz, 1H), 1.53 (s, 9H); 13C
NMR (101 MHz, CDCl3) δ 152.3, 148.6, 138.5, 132.5,
Acknowledgements
This work was financially supported by the Excellent Young
Scholars Research Fund of Beijing Institute of Technology (319-
0012331518 and 3190012331523), the National Natural Science
Foundation of China (21231002, 21671019), the 973 Program
7
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10.1002/adsc.201800919
Advanced Synthesis & Catalysis
(2014CB932103), and the International Science and Technology
Cooperation Project of BIT (3190012211808) for financial
support. We are grateful to Analytical and Testing Center in
Beijing Institute of Technology. We are also grateful to Dr. John
C.-G. Zhao at the University of Texas at San Antonio for helpful
language revision.
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Advanced Synthesis & Catalysis
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Pd-Catalyzed Synthesis of Indolines from
Aroyloxycarbamates through a Tandem
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Adv. Synth. Catal. Year, Volume, Page – Page
Zheng Wang,a Peihe Li,a Hui Fu,a John Cong-Gui
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