Concise Synthesis of Polycyclic Indoline Scaffolds through an InIII-Catalyzed Formal [4+2] Annulation of 2,3-Disubstituted Indoles with o-Aminobenzyl Alcohols

Article abstract of DOI:10.1002/ejoc.201700432

A concise indium(III)-catalyzed annulation of 2,3-disubstituted indoles with o-aminobenzyl alcohols is reported. The in situ generated aza-ortho-quinone methides (aza-oQMs) were efficiently trapped by diverse carbazoles in a formal [4+2] cycloaddition reaction catalyzed by indium(III) triflate, which provided rapid access to bridged polycyclic indoline alkaloid skeletons.

Full text of DOI:10.1002/ejoc.201700432

DOI: 10.1002/ejoc.201700432
Full Paper
Polycyclic Indolines
Concise Synthesis of Polycyclic Indoline Scaffolds through an
III
In -Catalyzed Formal [4+2] Annulation of 2,3-Disubstituted
Indoles with o-Aminobenzyl Alcohols
[
a,b]
[a,b]
[c]
[a,b]
Mupeng Luo,
Jianxin Chen,
Linqian Yu, and Wanguo Wei*
Abstract: A concise indium(III)-catalyzed annulation of 2,3-dis- addition reaction catalyzed by indium(III) triflate, which pro-
ubstituted indoles with o-aminobenzyl alcohols is reported. The vided rapid access to bridged polycyclic indoline alkaloid skele-
in situ generated aza-ortho-quinone methides (aza-oQMs) were tons.
efficiently trapped by diverse carbazoles in a formal [4+2] cyclo-
Introduction
Compared with ortho-quinone methides (o-QMs), the reac-
tions of in situ generated aza-oQMs under ambient conditions
are less explored, most likely because of their instability.
The polycyclic indoline framework is widely found in various
alkaloids and therapeutically important agents with diverse bio-
[
6]
Aza-oQMs are highly reactive intermediates and easily undergo
hetero-Diels–Alder reactions with electron-rich 2π-components,
conjugate additions with nucleophiles, and 6π-electron cycliza-
[
1]
logical activities. Representative examples include (+)-pero-
[
2]
[3]
[4]
phoramidine, communesin F, and vincorine, which exhibit
significant anticancer activity (Figure 1). Accordingly, over the
past decade, many effective approaches for the construction of
various 2,3-disubstituted polycyclic indoline scaffolds have
[
7]
tion reactions. Since 1995 when Corey and Steinhagen first
introduced aza-oQMs in [4+2] cycloaddition reactions by using
the base-mediated elimination of N-[(ortho-chloromethyl)aryl]
[
5]
been established. In this regard, we became interested in an
intermolecular cycloaddition approach to access such skeletons
in a single operation. Herein, we report the indium(III)-catalyzed
formal [4+2] cycloaddition between in situ generated aza-
ortho-quinone methides (aza-oQMs) and 2,3-disubstituted ind-
oles, which provides rapid and practical access to bridged poly-
cyclic indoline alkaloid skeletons as an elegant complement to
existing studies.
[
8]
amides, great success has been achieved by using aza-oQMs
as key intermediates in reactions with a wide variety of partners
for the synthesis of nitrogen-containing heterocyclic and natu-
[
9]
ral-product inspired scaffolds (Figure 2). For example, in 2012,
Xiao's group reported the formal [4+1] reaction of sulfur ylides
with N-[(ortho-chloromethyl)aryl] amides to prepare 2,3-disub-
[
9a]
stituted indoles (Figure 2). In 2014, the Scheidt group devel-
oped the N-heterocyclic carbene (NHC)/aza-oQM mediated syn-
[
10]
thesis of 2-arylindoles and dihydroquinolones.
The Verna
group reported an efficient [4+2] cycloaddition reaction be-
tween in situ generated aza-oQMs, from o-aminobenzyl alcohol,
[
11]
and internal alkynes to synthesize functionalized quinolines.
The Schneider group reported a phosphoric acid catalyzed for-
mal [4+2] cycloaddition of enamides with aza-oQMs for the syn-
[
12]
thesis of chiral tetrahydroacridines,
whereas the Rueping
group reported the Brønsted acid catalyzed reaction of in situ
generated aza-oQMs and 2-/3-substituted indoles to produce
Figure 1. Representative examples of indoline alkaloids.
[13]
diverse communesin and spiroindoline scaffolds.
Most re-
cently, the groups of Enders and Chen independently achieved
a formal [3+4] annulation of isatin-derived enals with in situ
[
a] Shanghai Advanced Research Institute, Chinese Academy of Sciences,
University of Chinese Academy of Sciences,
9
9 Haike Road, Shanghai 201210, P. R. China
E-mail: weiwg@sari.ac.cn
http://people.gucas.ac.cn/~weiwg?language=en
b] School of Life Science and Technology, ShanghaiTech University,
[
[
1
00 Haike Road, Shanghai 201210, P. R. China
c] School of Pharmarcy, Fudan University,
26 Zhangheng Road, Zhangjiang Hi-tech Park, Pudong
8
Shanghai 201203, P. R. China
Supporting information and ORCID(s) from the author(s) for this article are
available on the WWW under https://doi.org/10.1002/ejoc.201700432.
Figure 2. Aza-oQMs as key intermediates in the synthesis of natural-product
inspired scaffolds.
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generated aza-oQMs to synthesize spirobenzazepinones.[14,15]
Despite these great advances, the development of new strate-
gies that allow the direct and efficient construction of polycyclic
heterocycles by using aza-oQM equivalents is still highly fasci-
nating.
Table 1. Optimization of the reaction conditions.[a]
It is well known that aza-oQMs can be generated by various
methods including thermal extrusion, photolysis, and acid- or
[
11a,16]
base-mediated transformations.
However, the difficulty of
Entry
Solvent
Catalyst
T [°C]
t [h]
Yield [%][b]
its generation under ambient conditions has limited the use of
aza-oQMs as common electrophiles in catalysis and synthesis.
Besides N-[(ortho-chloromethyl)aryl] amides and o-aminobenzyl
halides, o-aminobenzyl alcohols have emerged as valuable pre-
cursors for the generation of reactive aza-oQMs under mild con-
1[c]
2
3
4
5
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
TFA
CSA[
TfOH
50
50
50
50
50
50
50
50
50
50
50
50
80
50
50
50
50
3
41
31
48
60
57
76
52
27
39
58
trace
64
trace
68
62
d]
24
24
20
3
24
3
48
12
20
48
20
20
24
24
24
24
Cu(OTf)2
Sc(OTf)
In(OTf)
Fe(OTf)
InCl
FeCl
3
[
11]
6
7
8
9
3
ditions without the need for preactivation. Early in 2011, the
Wu group reported the direct annulation of o-aminobenzyl al-
cohols with 3-substituted indoles catalyzed by trifluoroacetic
3
3
3
[
17]
[e]
acid to furnish 5,6-fused indolines.
conditions were not fully optimized, and the reactivities of
,3-disubstituted indoles remain severely underdeveloped. In-
However, the reaction
10
CH
2
Cl
O
2
In(OTf)
In(OTf)
In(OTf)
In(OTf)
In(OTf)
In(OTf)3
In(OTf)
In(OTf)
3
3
3
3
3
1
1
1
1
1
2
3
4
H
2
dioxane
CH CN
2
3
trigued by this pioneering work as well as recent discoveries in
the area of aza-oQM chemistry, we anticipated that aza-oQMs
generated in situ from ortho-aminobenzyl alcohols could un-
dergo an intramolecular [4+2]-type cycloaddition with 2,3-
disubstituted indoles. This transformation would give direct ac-
cess to 2,2,3,3-tetrasubstituted bridged indoline scaffolds that
contain contiguous tetrasubstituted carbon atoms (Figure 2).
toluene
THF[
d]
15
[
f]
16
DCE
DCE
3
78
78
[g]
1
7
3
[a] Reagents and conditions [on a 0.5 mmol scale (0.1
tetrahydro-1H-carbazole (1a; 2.0 equiv.), o-aminobenzyl alcohol (2a;
.0 equiv.), and catalyst (10 mol-% catalyst) in solvent (5.0 mL), unless other-
wise noted. [b] Isolated yields after silica gel column chromatography. [c] This
reaction used 30 % trifluoroacetic acid in 1,2-dichloroethane. [d] CSA = cam-
phorsulfonic acid; THF = tetrahydrofuran. [e] The reaction was conducted in
M
)]: 9-methyl-2,3,4,9-
1
sealed glass tubes. [f] MgSO
ular sieves (4 Å) were added to the reaction mixture.
4
was added to the reaction mixture. [g] Molec-
Results and Discussion
Our study began with the reaction of 9-methyl-1,2,3,4-tetra-
hydrocarbazole (1a) and ortho-aminobenzyl alcohol (2a) in the
presence of 30 % trifluoroacetic acid (TFA) and with 1,2- smoothly underwent the reaction with o-aminobenzyl alcohol
dichloroethane as the solvent (within 3 h at 50 °C). Under these (2a) to provide the desired cycloadducts in excellent yields (66–
conditions, the reaction afforded the desired cycloadduct 3a in 78 %; Table 2; compounds 3a–3c). Next, a wide variety of sub-
[
17]
poor yield (41 %; Table 1, Entry 1). To find the optimum reac- stituted tetrahydrocarbazoles that contain an electron-donating
2
tion conditions, we screened a number of Lewis acids (Table 1, (i.e., R = Me, MeO, or OCH O) or electron-withdrawing group
2
2
Entries 4–9). As shown in Table 1, many of them were found (i.e., R = OCF , CF , Br, F, CN, or CO Me) were examined. All of
3
3
2
to catalyze this cycloaddition reaction, but the best yield was these substrates easily participated in this reaction to furnish
obtained by using In(OTf) (OTf = trifluoromethanesulfonate; the corresponding cycloadducts in moderate to good yields
3
Table 1, Entry 6). When the reaction was carried out in DCE (49–69 %; Table 2; compounds 3d–3m). Slightly decreased
(
1,2-dichloroethane) with In(OTf) (10 mol-%) as the Lewis acid yields, however, resulted from the substrates with electron-
3
catalyst, 3a was obtained in an excellent yield (76 %) along with withdrawing substituents. In addition, N-substituted ethyl
other side products (for details, see the Supporting Informa- 1,3,4,9-tetrahydro-2H-pyrido[3,4-b]indole-2-carboxylate
was
tion). Different solvents were employed to further optimize the also well tolerated and afforded the structurally more diverse
reaction conditions. A series of common organic solvents were cycloadduct 3n in 85 % yield. Moreover, we evaluated different
found to support this formal [4+2] cycloaddition reaction and carbon ring systems that were also fused at the 2- and 3-posi-
afforded 3a in moderate to excellent yields with a catalyst load- tions of the indole. Notably, a cyclopentane-fused indole under-
ing of 10 mol-% (Table 1, Entries 10–15), but 1,2-dichloroethane went the reaction faster and afforded a better yield (93 %;
was found to be superior to the other solvents investigated Table 2; compound 3o) with a higher selectivity than the cyclo-
herein. The addition of MgSO or molecular sieves to the reac- hexane-fused indoles. In contrast, cycloheptane-fused indoles
4
tion led to a slight increase in the yield (Table 1, Entries 16 and gave no desired cyclization product under the optimized reac-
17).
tion conditions (data not shown).
With the optimal reaction conditions established, the scope
Subsequently, the scope in relation to the alcohols 2 was
as well as the generality of the present method was investi- also investigated under the optimized conditions. Initially, the
gated with regard to functionally various 2,3-disubstituted ind- effect of a substituent on the nitrogen atom was examined. A
3
oles 1 (Table 2). Indoles that contained N-H, N-methyl, and N- wide range of N-alkyl substituents (i.e., R ) were tolerated in the
1
benzyl groups (R = H, Me, Bn) were found to be suitable and reactions with cyclopentane- or cyclohexane-fused indoles to
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Table 2. Scope of 2,3-disubstituted indoles in formal [4+2] cycloaddition.[a,b]
Table 3. Scope of o-aminobenzyl alcohols in formal [4+2] cycloaddition.[a,b]
[
a] Reagents and conditions: 1 (1.0 mmol, 2.0 equiv.), 2 (0.5 mmol, 1.0 equiv.),
and In(OTf) (28 mg, 10 mol-%) in DCE (5.0 mL) at 50 °C for 24 h. [b] Isolated
3
yields after silica gel column chromatography. [c] PMB = para-methoxybenzyl.
reaction smoothly with 9-methyl-2,3,4,9-tetrahydro-1H-carbaz-
[
1
[
a] Reagents and conditions: 1 (1.0 mmol, 2.0 equiv.), 2a (0.5 mmol,
.0 equiv.), and In(OTf) (28 mg, 10 mol-%) in DCE (5.0 mL) at 50 °C for 24 h.
b] Isolated yields after silica gel column chromatography.
ole (1a) in the presence of 10 mol-% of In(OTf)
exclusively afford endo cycloadduct 6a in 96 % yield
Scheme 1). The configuration at the C-11–Ar bond of 6a was
at 50 °C to
3
3
(
assigned by NOE experiments, which showed a cis relationship
between the protons of the cyclohexyl group and that of the
C-11–H bond (see the Supporting Information for details). The
high diastereoselectivity of this reaction could be ascribed to
provide bridged indoline adducts in excellent yield (68–96 %;
Table 3; compounds 4a–4e). Remarkably, a sterically hindered
3
N-aryl substituent (e.g., R = phenyl) was also well tolerated and
afforded 4f in 86 % yield. However, an electron-withdrawing
substituent such as a para-tolylsulfonyl (Ts) or an acetyl (Ac)
group on the nitrogen atom of 2 did not afford the expected
product, and no reaction occurred. Subsequently, screening of
different substituents on the aromatic ring of the o-amino-
benzyl alcohol was also carried out, and we found that the
reaction was highly dependent on the electronic nature of
those groups. The o-aminobenzyl alcohols that contained an
4
electron-rich (e.g., R = Me) or weak electron-withdrawing
4
group (e.g., R = Cl) on the phenyl ring were tolerated and
afforded the desired cycloadducts in excellent yields (69–97 %;
Table 3; compounds 4g–4l). Those substrates 2 that contained
4
a strong electron-withdrawing group (e.g., R = CF ) did not
3
give the desired cycloadduct, and no reaction occurred.
To further extend the scope of this aza-oQM-mediated cyclo-
addition reaction, we examined secondary o-aminobenzyl alco-
hols. Gratifyingly, the in situ generated aza-oQM underwent a
Scheme 1. Reaction of o-aminobenzyl alcohol 5 with 1a.
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the Z selectivity of the azadiene and the π-π stacking interac- 0.00 ppm) or residual CHCl
(δ = 7.26 ppm). The chemical shifts for
3
the 13C NMR data are reported in ppm relative to CDCl (δ =
tions between the indole ring and aromatic ring of the aza-
oQM, which favor an endo-type cyclization.
Consistent with what has previously been proposed, this re-
action may proceed through an aza-ortho-quinone methide
3
1
7
(
7.16 ppm). The H NMR data are reported as follows: chemical shift
δ, ppm), multiplicity [s (singlet), d (doublet), t (triplet), m (multiplet
or unresolved), br. s (broad singlet)], coupling constant(s) in Hz,
integration. The 13C NMR data are reported in terms of chemical
shift values (δ, ppm). HR mass spectra were recorded with an
Agilent Technologies 6230 TOF LC/MS spectrometer. Solvents for
flash chromatography (FC) were of technical grade and distilled
(
aza-oQM) intermediate, which is generated through the intra-
molecular hydrogen-bond activation of the alcohol by the adja-
[
11,17]
cent protonated aniline nitrogen atom.
Cyclization can oc-
cur either in a stepwise or concerted fashion. Interestingly, we prior to use. Column chromatography was performed on silica gel
observed that heating of a solution of 3a in 1,2-dichloroethane (200–300 mesh) by eluting with ethyl acetate and hexanes. TLC was
performed on glass-backed silica plates.
at 80 °C for 12 h fully induced a retro-Diels–Alder (DA) process.
From this, we were able to isolate 9-methyl-1,2,3,4-tetrahydro-
General Procedure for the Synthesis of Compounds 3a–3o and
carbazole (1a) in 24 % isolated yield, C-6 nucleophilic adduct 7 4a–4l: A mixture of the tetrahydro-1H-carbazole (1.0 mmol,
in 14 % isolated yield, and C-8 nucleophilic adduct 8 in 18 % 2.0 equiv.), the 2-aminobenzyl alcohol derivative (0.5 mmol,
1
1
2
.0 equiv.), molecular sieves (4 Å; 100 mg), and In(OTf)3 (28 mg,
0 mol-%) in 1,2-dichloroethane (5.0 mL) was stirred at 50 °C for
4 h. Upon completion of the reaction, the mixture was cooled to
isolated yield (Scheme 2). These results provide direct evidence
for the involvement of the aza-oQM intermediate in this formal
[
4+2] annulation.
room temperature. The organic layer was separated and washed
with an aqueous NaHCO solution. The aqueous layer was extracted
3
with dichloromethane (3 ×). The combined organic layers were
washed with brine and then dried with anhydrous Na SO . The mix-
2
4
ture was filtered, and the filtrate was concentrated. The remaining
residue was purified by column chromatography on silica gel (ethyl
acetate and hexanes) to give the corresponding product (i.e., 3a–
3o and 4a–4l).
6
-Methyl-5,11-dihydro-6H-5a,10b-butanoindolo[2,3-b]quinol-
ine (3a): The preparation was carried out according to the general
procedure. Purification by silica gel column chromatography (2 %
1
ethyl acetate/hexanes) gave 3a (78 % yield) as a white solid.
H
NMR (500 MHz, CDCl ): δ = 7.04 (t, J = 7.6 Hz, 1 H), 7.01–6.93 (m, 2
3
H), 6.87 (d, J = 7.3 Hz, 1 H), 6.67 (t, J = 7.4 Hz, 1 H), 6.60–6.50 (m, 2
H), 6.36 (d, J = 7.7 Hz, 1 H), 3.65 (s, 1 H), 2.81 (d, J = 15.5 Hz, 1 H),
Scheme 2. Retro-[4+2]-cycloaddition reaction of 3a.
2
1
.59 (s, 3 H), 2.22 (d, J = 15.6 Hz, 1 H), 1.90 (d, J = 15.3 Hz, 1 H),
.52 (d, J = 13.5 Hz, 1 H), 1.41 (dt, J = 13.2, 6.9 Hz, 3 H), 1.28 (td,
J = 13.3, 3.5 Hz, 1 H), 1.17 (dddd, J = 27.0, 13.6, 7.0, 2.7 Hz, 2 H)
Conclusions
13
ppm. C NMR (126 MHz, CDCl ): δ = 148.90, 141.62, 135.60, 129.11,
3
1
4
27.55, 127.03, 120.90, 120.85, 117.85, 117.39, 112.91, 107.76, 81.80,
We have developed an efficient indium(III)-catalyzed formal
1.62, 39.09, 31.58, 28.00, 27.10, 22.27, 21.66 ppm. HRMS (ESI-TOF):
[
4+2] cycloaddition of 2,3-disubstituted indoles with aza-ortho-
+
calcd. for C H N [M + H] 291.1861; found 291.1860.
20 22 2
quinone methides, generated from o-aminobenzyl alcohols, for
the rapid construction of bridged polycyclic indoline derivatives
that have two contiguous tetrasubstituted carbon centers. The
reaction affords excellent regioselectivity through the in situ
formation of the aza-ortho-quinone methide followed by trap-
ping with the 2,3-disubstituted indole. The present method tol-
erates a diverse range of 2,3-disubstituted indoles and o-amino-
5
,11-Dihydro-6H-5a,10b-butanoindolo[2,3-b]quinoline (3b): The
preparation was carried out according to the general procedure.
Purification by silica gel column chromatography (5 % ethyl acetate/
hexanes) gave 3b (66 % yield) as a white solid. H NMR (500 MHz,
CDCl ): δ = 7.10 (dd, J = 7.3, 1.2 Hz, 1 H), 7.07–6.99 (m, 2 H), 6.95
1
3
(dt, J = 7.4, 1.3 Hz, 1 H), 6.80 (td, J = 7.4, 1.0 Hz, 1 H), 6.68–6.60 (m,
2
H), 6.55 (dd, J = 7.9, 1.1 Hz, 1 H), 3.96 (s, 1 H), 2.91 (d, J = 15.6 Hz,
benzyl alcohols and affords products in good to excellent 1 H), 2.37 (d, J = 15.7 Hz, 1 H), 2.01–1.93 (m, 1 H), 1.81 (ddd, J =
yields. Compared with previous studies, the scope of the 2,3- 13.7, 12.4, 3.7 Hz, 1 H), 1.66 (ddt, J = 13.4, 4.9, 2.1 Hz, 1 H), 1.54–
1
.46 (m, 2 H), 1.41–1.25 (m, 3 H) ppm. 13C NMR (126 MHz, CDCl3):
disubsitued indoles and the o-aminobenzyl alcohols has been
widely expanded. Further studies of an asymmetric heterocyclo-
addition and its application toward the synthesis of natural
products are under investigation, and our findings will be dis-
closed in due course.
δ = 147.68, 141.72, 136.28, 129.05, 127.40, 127.08, 121.73, 120.58,
1
2
2
19.31, 117.36, 112.84, 111.06, 78.94, 42.54, 38.81, 37.68, 28.48,
2.17, 22.14 ppm. HRMS (ESI-TOF): calcd. for C H N [M + H]+
77.1705; found 277.1703.
19 20 2
6
-Benzyl-5,11-dihydro-6H-5a,10b-butanoindolo[2,3-b]quinol-
ine (3c): The preparation was carried out according to the general
procedure. Purification by silica gel column chromatography (0.3 %
ethyl acetate/hexanes) gave 3c (67 % yield) as a white solid. H NMR
Experimental Section
General Methods: All of the H and 13C NMR spectroscopic data
1
1
(500 MHz, CDCl ): δ = 7.33 (d, J = 7.2 Hz, 2 H), 7.24 (dd, J = 8.3,
3
were recorded with a Bruker Avance III HD 500 MHz spectrometer.
6.5 Hz, 2 H), 7.19 (dd, J = 8.4, 6.1 Hz, 1 H), 7.11 (dd, J = 7.3, 1.3 Hz,
1 H), 7.09–7.01 (m, 2 H), 6.97 (td, J = 7.7, 1.3 Hz, 1 H), 6.77–6.67 (m,
2 H), 6.59–6.54 (m, 1 H), 6.20 (d, J = 7.7 Hz, 1 H), 4.55 (d, J = 15.2 Hz,
CDCl was used as the NMR solvent. The chemical shifts (δ-scale)
3
1
for the H NMR data are reported in ppm relative to TMS (δ =
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1
1
1
H), 3.90 (d, J = 15.2 Hz, 1 H), 3.15 (d, J = 15.4 Hz, 1 H), 2.39 (d, J = 6-Methyl-8-(trifluoromethyl)-5,11-dihydro-6H-5a,10b-butano-
5.5 Hz, 1 H), 2.07–2.00 (m, 1 H), 1.70–1.63 (m, 2 H), 1.53 (ddq, J = indolo[2,3-b]quinoline (3h): The preparation was carried out ac-
1
3
2.9, 6.2, 3.5 Hz, 2 H), 1.45–1.18 (m, 3 H) ppm. C NMR (126 MHz,
cording to the general procedure. Purification by silica gel column
CDCl ): δ = 148.19, 141.63, 139.86, 135.54, 129.02, 128.47, 127.35, chromatography (1 % ethyl acetate/hexanes) gave 3h (49 % yield)
3
1
1
27.19, 127.01, 126.79, 120.96, 120.87, 117.86, 117.40, 113.01,
as a white solid. H NMR (500 MHz, CDCl ): δ = 7.12 (d, J = 7.5 Hz,
3
1
08.54, 82.24, 45.99, 41.75, 39.21, 32.78, 27.81, 22.12, 21.73 ppm. 1 H), 7.10–7.05 (m, 1 H), 7.02–6.95 (m, 2 H), 6.68 (td, J = 7.3, 1.2 Hz,
HRMS (ESI-TOF): calcd. for C26H26N2 [M + H]+ 367.2174; found
1 H), 6.64 (dd, J = 7.9, 1.2 Hz, 1 H), 6.58 (d, J = 1.5 Hz, 1 H), 4.10 (s,
1 H), 2.87 (d, J = 15.5 Hz, 1 H), 2.72 (s, 3 H), 2.32 (d, J = 15.6 Hz, 1
H), 2.00 (d, J = 12.4 Hz, 1 H), 1.66 (d, J = 13.1 Hz, 1 H), 1.57–1.48
3
67.2172.
6
,7,9-Trimethyl-5,11-dihydro-6H-5a,10b-butanoindolo[2,3-b]-
1
3
(
(
m, 2 H), 1.48–1.34 (m, 2 H), 1.30–1.17 (m, 2 H) ppm. C NMR
quinoline (3d): The preparation was carried out according to the
general procedure. Purification by silica gel column chromatogra-
phy (1.3 % ethyl acetate/hexanes) gave 3d (67 % yield) as a white
solid. H NMR (500 MHz, CDCl ): δ = 7.06 (t, J = 7.6 Hz, 1 H), 6.95
126 MHz, CDCl ): δ = 149.23, 141.39, 139.40, 130.10, 129.85, 129.14,
3
1
27.24, 125.92, 123.76, 120.84, 120.49, 117.74, 114.88, 114.84,
114.81, 114.78, 113.07, 103.64, 103.61, 103.58, 103.55, 82.14, 41.88,
8.73, 31.87, 27.93, 26.79, 22.24, 21.45 ppm. HRMS (ESI-TOF): calcd.
1
3
3
(d, J = 7.3 Hz, 1 H), 6.78 (s, 1 H), 6.70 (s, 1 H), 6.65 (dd, J = 12.9,
+
for C H F N [M + H] 359.1735; found 359.1733.
21 21 3 2
7
2
.6 Hz, 2 H), 4.11 (s, 1 H), 2.96 (s, 3 H), 2.85 (d, J = 15.6 Hz, 1 H),
.40 (s, 3 H), 2.28 (s, 4 H), 1.96 (dt, J = 10.3, 2.3 Hz, 1 H), 1.69–1.58
9-Bromo-6-methyl-5,11-dihydro-6H-5a,10b-butanoindolo-
[2,3-b]quinoline (3i): The preparation was carried out according to
the general procedure. Purification by silica gel column chromatog-
(m, 2 H), 1.58–1.47 (m, 2 H), 1.39–1.29 (m, 2 H), 1.24 (dddd, J = 19.3,
1
3
1
1
3
6.8, 7.2, 4.9 Hz, 1 H) ppm. C NMR (126 MHz, CDCl ): δ = 141.57,
3
31.67, 129.12, 127.04, 120.72, 119.76, 117.39, 112.91, 41.32, 39.72,
raphy (1 % ethyl acetate/hexanes) gave 3i (62 % yield) as a white
1
2.11, 30.36, 27.98, 22.22, 22.04, 20.90, 19.64 ppm. HRMS (ESI-TOF):
solid. H NMR (500 MHz, CDCl ): δ = 7.20 (dd, J = 8.1, 2.1 Hz, 1 H),
3
+
calcd. for C H N [M + H] 319.2174; found 319.2180.
7.14 (d, J = 2.1 Hz, 1 H), 7.06 (t, J = 7.6 Hz, 1 H), 6.96 (d, J = 7.3 Hz,
22 26 2
1
6
H), 6.66 (td, J = 7.3, 1.1 Hz, 1 H), 6.62 (dd, J = 7.9, 1.0 Hz, 1 H),
.29 (d, J = 8.1 Hz, 1 H), 2.87 (d, J = 15.6 Hz, 1 H), 2.65 (s, 3 H), 2.30
9
-Methoxy-6-methyl-5,11-dihydro-6H-5a,10b-butanoindolo-
[2,3-b]quinoline (3e): The preparation was carried out according
(d, J = 15.6 Hz, 1 H), 1.93 (dd, J = 13.9, 2.2 Hz, 1 H), 1.66–1.59 (m, 1
to the general procedure. Purification by silica gel column chroma-
tography (2 % ethyl acetate/hexanes) gave 3e (69 % yield) as a
white solid. H NMR (500 MHz, CDCl ): δ = 7.08–7.02 (m, 1 H), 6.96
(
13
H), 1.55–1.43 (m, 2 H), 1.40–1.14 (m, 4 H) ppm. C NMR (126 MHz,
CDCl ): δ = 147.97, 141.37, 137.88, 130.16, 129.15, 127.18, 124.17,
20.50, 117.65, 113.01, 109.33, 109.01, 81.89, 41.96, 38.94, 31.64,
7.92, 26.90, 22.24, 21.51 ppm. HRMS (ESI-TOF): calcd. for
1
3
3
1
2
d, J = 7.2 Hz, 1 H), 6.76 (d, J = 2.6 Hz, 1 H), 6.69–6.60 (m, 3 H),
.44–6.29 (m, 1 H), 4.11 (s, 1 H), 3.80 (s, 3 H), 2.93 (d, J = 15.5 Hz, 1
H), 2.65 (s, 3 H), 2.32 (d, J = 15.6 Hz, 1 H), 1.95 (dd, J = 13.7, 2.3 Hz,
H), 1.59 (d, J = 13.7 Hz, 1 H), 1.52 (d, J = 13.5 Hz, 3 H), 1.41–1.33 9-Fluoro-6-methyl-5,11-dihydro-6H-5a,10b-butanoindolo-
6
+
C H BrN [M + H] 369.0966; found 369.0963.
20
21
2
1
1
3
(m, 1 H), 1.33–1.17 (m, 2 H) ppm. C NMR (126 MHz, CDCl ): δ =
[2,3-b]quinoline (3j): The preparation was carried out according to
3
1
1
2
52.88, 143.34, 141.61, 137.34, 129.16, 127.05, 120.68, 117.36,
12.95, 110.89, 109.38, 107.78, 81.63, 56.03, 41.90, 38.99, 31.06,
8.14, 27.56, 22.30, 21.82 ppm. HRMS (ESI-TOF): calcd. for C H N O
the general procedure. Purification by silica gel column chromatog-
raphy (1 % ethyl acetate/hexanes) gave 3j (63 % yield) as a white
1
solid. H NMR (500 MHz, CDCl ): δ = 7.06 (t, J = 7.6 Hz, 1 H), 6.97
21
24
2
3
+
[
M + H] 321.1967; found 321.1961.
(d, J = 7.4 Hz, 1 H), 6.86–6.75 (m, 2 H), 6.70–6.60 (m, 2 H), 6.34 (dd,
J = 8.5, 4.1 Hz, 1 H), 2.90 (d, J = 15.5 Hz, 1 H), 2.65 (s, 3 H), 2.32 (d,
J = 15.5 Hz, 1 H), 1.95–1.88 (m, 1 H), 1.66–1.58 (m, 1 H), 1.50 (td,
J = 13.3, 12.7, 8.1 Hz, 3 H), 1.41–1.33 (m, 1 H), 1.29–1.19 (m, 2 H)
5
-Methyl-6,11-dihydro-5H-5a,11a-butano[1,3]dioxolo[4′,5′:5,6]-
indolo[2,3-b]quinoline (3f): The preparation was carried out ac-
cording to the general procedure. Purification by silica gel column
chromatography (1 % ethyl acetate/hexanes) gave 3f (66 % yield)
as a white solid. H NMR (500 MHz, CDCl ): δ = 7.05 (t, J = 7.6 Hz,
ppm. 13C NMR (126 MHz, CDCl ): δ = 157.71, 155.84, 145.06, 141.45,
3
1
137.45, 129.15, 127.17, 120.45, 117.55, 113.09, 113.02, 112.91,
3
1
09.26, 109.07, 107.86, 82.02, 41.97, 38.85, 31.27, 28.14, 27.53, 22.26,
1
(
H), 6.95 (d, J = 7.3 Hz, 1 H), 6.70–6.59 (m, 3 H), 6.18 (s, 1 H), 5.88
d, J = 18.9 Hz, 2 H), 2.87 (d, J = 15.6 Hz, 1 H), 2.64 (s, 3 H), 2.31 (d,
J = 15.5 Hz, 1 H), 1.88 (dq, J = 13.6, 2.6 Hz, 1 H), 1.68–1.46 (m, 4 H),
+
21.65 ppm. HRMS (ESI-TOF): calcd. for C H FN [M + H] 309.1767;
20
21
2
found 309.1762.
1
3
1
1
1
2
3
.39–1.16 (m, 4 H) ppm. C NMR (151 MHz, CDCl ): δ = 146.65, 9-Bromo-7-fluoro-6-methyl-5,11-dihydro-6H-5a,10b-butano-
3
44.48, 141.62, 139.23, 129.11, 127.54, 127.04, 120.88, 117.42,
indolo[2,3-b]quinoline (3k): The preparation was carried out ac-
12.92, 103.30, 100.49, 92.13, 81.87, 41.63, 39.15, 31.21, 28.26, 27.46, cording to the general procedure. Purification by silica gel column
+
2.26, 21.76 ppm. HRMS (ESI-TOF): calcd. for C H N O [M + H]
chromatography (1 % ethyl acetate/hexanes) gave 3k (55 % yield)
2
1 22 2 2
1
35.1760; found 335.1759.
as a white solid. H NMR (500 MHz, CDCl ): δ = 7.10–7.04 (m, 1 H),
3
7
1
2
.01 (dd, J = 11.3, 1.8 Hz, 1 H), 6.99–6.94 (m, 2 H), 6.68 (td, J = 7.4,
.2 Hz, 1 H), 6.63 (dd, J = 8.0, 1.1 Hz, 1 H), 4.08 (s, 1 H), 2.91 (d, J =
.9 Hz, 3 H), 2.86 (d, J = 15.5 Hz, 1 H), 2.28 (d, J = 15.6 Hz, 1 H), 1.90
6
-Methyl-9-(trifluoromethoxy)-5,11-dihydro-6H-5a,10b-but-
anoindolo[2,3-b]quinoline (3g): The preparation was carried out
according to the general procedure. Purification by silica gel column
chromatography (1 % acetate/hexanes) gave 3g (65 % yield) as a
white solid. H NMR (500 MHz, CDCl ): δ = 7.09 (t, J = 7.6 Hz, 1 H),
(dq, J = 13.5, 2.6, 2.2 Hz, 1 H), 1.74–1.67 (m, 1 H), 1.58 (ddd, J =
13
1
29.3, 12.3, 7.3 Hz, 3 H), 1.41–1.16 (m, 3 H) ppm. C NMR (126 MHz,
CDCl ): δ = 150.32, 148.37, 141.11, 140.81, 140.76, 134.52, 134.45,
1
1
3
3
6
1
.98 (dd, J = 12.2, 5.1 Hz, 3 H), 6.73–6.68 (m, 1 H), 6.66 (d, J = 8.0 Hz,
H), 6.37 (d, J = 8.2 Hz, 1 H), 3.75 (s, 1 H), 2.92 (d, J = 15.5 Hz, 1
29.10, 127.26, 120.34, 120.32, 120.24, 118.84, 118.65, 117.78,
13.09, 108.02, 107.95, 82.31, 42.69, 38.72, 31.76, 28.16, 28.11, 28.02,
H), 2.70 (s, 3 H), 2.34 (d, J = 15.5 Hz, 1 H), 2.00–1.92 (m, 1 H), 1.65
+
2
2.17, 21.60 ppm. HRMS (ESI-TOF): calcd. for C H BrFN [M + H]
20
20
2
(dq, J = 13.6, 3.0, 2.5 Hz, 1 H), 1.60–1.46 (m, 3 H), 1.41 (td, J = 13.9,
1
3
387.0872; found 387.0873.
1
3.5, 3.7 Hz, 1 H), 1.34–1.18 (m, 2 H) ppm. C NMR (126 MHz,
CDCl ): δ = 147.67, 141.41, 141.13, 136.89, 129.13, 127.19, 123.95, 6-Methyl-5,11-dihydro-6H-5a,10b-butanoindolo[2,3-b]quin-
3
1
4
21.92, 120.48, 119.90, 117.87, 117.66, 115.16, 113.02, 107.19, 82.05,
oline-9-carbonitrile (3l): The preparation was carried out accord-
ing to the general procedure. Purification by silica gel column chro-
matography (7 % ethyl acetate/hexanes) gave 3l (53 % yield) as a
1.88, 38.82, 31.58, 27.90, 26.99, 22.20, 21.49 ppm. HRMS (ESI-TOF):
+
calcd. for C H F N O [M + H] 375.1684; found 375.1688.
21 21 3 2
Eur. J. Org. Chem. 2017, 2652–2660
www.eurjoc.org
2656
© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
1
white solid. H NMR (500 MHz, CDCl ): δ = 7.44 (d, J = 8.1 Hz, 1 H),
7
6
2 H), 7.08 (dd, J = 7.2, 1.2 Hz, 1 H), 7.01–6.93 (m, 2 H), 6.89 (dd, J =
8.2, 3.5 Hz, 3 H), 6.75 (d, J = 8.0 Hz, 1 H), 6.66 (t, J = 7.3 Hz, 1 H),
6.60 (t, J = 7.3 Hz, 1 H), 6.10 (d, J = 7.8 Hz, 1 H), 4.89 (s, 2 H), 3.80
3
.28 (s, 1 H), 7.10 (t, J = 7.6 Hz, 1 H), 6.99 (d, J = 7.3 Hz, 1 H), 6.77–
.66 (m, 2 H), 6.40 (d, J = 8.1 Hz, 1 H), 4.33 (s, 1 H), 2.85–2.74 (m, 4
H), 2.35 (d, J = 15.5 Hz, 1 H), 2.02–1.95 (m, 1 H), 1.78 (d, J = 13.6 Hz, (s, 3 H), 3.26 (d, J = 13.3 Hz, 1 H), 3.03 (d, J = 13.3 Hz, 1 H), 2.94 (s,
1
9
H), 1.63–1.50 (m, 2 H), 1.45 (q, J = 11.2, 8.9 Hz, 2 H), 1.26 (p, J = 3 H), 2.66 (dd, J = 12.2, 5.4 Hz, 1 H), 2.31 (dtd, J = 24.7, 12.2, 6.0 Hz,
.2, 7.8 Hz, 2 H) ppm. 1 C NMR (126 MHz, CDCl ): δ = 152.00, 140.72,
3
2 H), 2.18 (td, J = 12.6, 5.9 Hz, 1 H), 1.89 (dt, J = 11.9, 5.8 Hz, 1 H),
3
1
1
35.86, 133.78, 128.96, 127.32, 124.32, 121.11, 120.66, 118.45,
13.54, 106.66, 98.58, 82.74, 42.19, 38.84, 32.20, 27.90, 26.33, 21.70,
1.58 (qt, J = 12.4, 6.0 Hz, 1 H) ppm. 13C NMR (126 MHz, CDCl ): δ =
3
158.39, 152.28, 144.82, 133.77, 131.66, 131.10, 127.68, 127.57,
127.32, 126.40, 122.19, 119.82, 116.10, 115.42, 113.86, 102.91, 96.16,
63.34, 55.21, 49.23, 43.98, 40.67, 37.30, 30.16, 24.00 ppm. HRMS (ESI-
+
2
0.76 ppm. HRMS (ESI-TOF): calcd. for C H N [M + H] 316.1814;
2
1 21 3
found 316.1819.
+
TOF): calcd. for C H N O [M + H] 397.2280; found 397.2283.
27 28 2
Methyl 6-Methyl-5,11-dihydro-6H-5a,10b-butanoindolo-
2,3-b]quinoline-9-carboxylate (3m): The preparation was carried
[
6-Methyl-5-(thiophen-2-ylmethyl)-5,11-dihydro-6H-5a,10b-
propanoindolo[2,3-b]quinoline (4b): The preparation was carried
out according to the general procedure. Purification by silica gel
out according to the general procedure. Purification by silica gel
column chromatography (3 % ethyl acetate/hexanes) gave 3m
1
(51 % yield) as a white solid. H NMR (500 MHz, CDCl ): δ = 7.90
column chromatography (0.3 % ethyl acetate/hexanes) gave 4b
3
1
(dd, J = 8.1, 1.8 Hz, 1 H), 7.76 (d, J = 1.8 Hz, 1 H), 7.08 (t, J = 7.6 Hz,
(90 % yield) as a white solid. H NMR (500 MHz, CDCl ): δ = 7.13 (d,
3
1
8
2
H), 6.97 (d, J = 7.3 Hz, 1 H), 6.71 (t, J = 7.3 Hz, 2 H), 6.40 (d, J = J = 5.0 Hz, 1 H), 7.07 (dd, J = 7.3, 1.3 Hz, 1 H), 7.05–6.94 (m, 4 H),
.2 Hz, 1 H), 5.26 (s, 1 H), 3.90 (s, 3 H), 2.84 (d, J = 15.5 Hz, 1 H), 6.90 (dd, J = 7.7, 3.7 Hz, 2 H), 6.70 (t, J = 7.1 Hz, 1 H), 6.60 (t, J =
.77 (s, 3 H), 2.39 (d, J = 15.5 Hz, 1 H), 2.06 (dd, J = 14.6, 3.5 Hz, 1
7.3 Hz, 1 H), 6.09 (d, J = 7.7 Hz, 1 H), 5.23 (d, J = 15.9 Hz, 1 H), 5.00
(d, J = 15.9 Hz, 1 H), 3.22 (d, J = 13.2 Hz, 1 H), 3.02 (d, J = 13.2 Hz,
1 H), 2.89 (s, 3 H), 2.64 (dd, J = 12.1, 5.5 Hz, 1 H), 2.28 (dddd, J =
37.3, 18.3, 12.3, 6.4 Hz, 3 H), 1.90 (dt, J = 11.8, 5.8 Hz, 1 H), 1.58 (qt,
H), 1.75 (dd, J = 13.0, 3.6 Hz, 1 H), 1.59–1.37 (m, 4 H), 1.34–1.16 (m,
2
1
1
2
3
H) ppm. 13C NMR (126 MHz, CDCl ): δ = 167.82, 152.66, 140.90,
3
34.97, 131.34, 129.00, 127.17, 122.51, 121.02, 118.78, 118.25,
13.42, 106.13, 82.77, 51.70, 41.96, 38.99, 32.14, 27.95, 26.53, 21.82,
J = 12.4, 6.1 Hz, 1 H) ppm. 13C NMR (126 MHz, CDCl ): δ = 152.14,
3
+
0.95 ppm. HRMS (ESI-TOF): calcd. for C22H24N O [M + H]
145.25, 144.37, 133.62, 131.46, 127.56, 127.41, 126.64, 126.40,
123.75, 123.68, 122.22, 120.32, 116.18, 114.89, 102.90, 96.11, 63.47,
2
2
49.1916; found 349.1917.
4
5.64, 43.84, 40.57, 37.16, 29.82, 24.07 ppm. HRMS (ESI-TOF): calcd.
Ethyl 6-Methyl-5,11-dihydro-6H-5a,10b-(ethanoiminometh-
ano)indolo[2,3-b]quinoline-14-carboxylate (3n): The preparation
+
for C H N S [M + H] 373.1738; found 373.1742.
24 24 2
was carried out according to the general procedure. Purification by 3,5-Dimethyl-4-{[6-methyl-6H-5a,10b-propanoindolo[2,3-b]quin-
silica gel column chromatography (10 % ethyl acetate/hexanes)
gave 3n (85 % yield) as a white solid. H NMR (500 MHz, CDCl3):
olin-5(11H)-yl]methyl}isoxazole (4c): The preparation was carried
out according to the general procedure. Purification by silica gel
1
δ = 7.15 (dd, J = 35.8, 7.3 Hz, 1 H), 7.08 (t, J = 7.6 Hz, 1 H), 7.03 (t,
J = 7.5 Hz, 1 H), 6.93 (d, J = 7.4 Hz, 1 H), 6.70 (t, J = 7.5 Hz, 1 H),
column chromatography (3 % ethyl acetate/hexanes) gave 4c (95 %
1
yield) as a white solid. H NMR (500 MHz, CDCl ): δ = 6.96 (dd, J =
3
6
1
2
.66 (t, J = 7.3 Hz, 1 H), 6.62 (d, J = 7.3 Hz, 1 H), 6.38 (t, J = 8.8 Hz,
H), 4.23 (q, J = 15.6, 14.5 Hz, 2 H), 4.08 (dtd, J = 28.1, 14.7, 7.2 Hz,
H), 3.98–3.69 (m, 1 H), 3.14–2.86 (m, 3 H), 2.70 (s, 3 H), 2.55 (dd,
7.2, 1.3 Hz, 1 H), 6.91 (dtd, J = 13.4, 7.7, 1.4 Hz, 2 H), 6.83 (d, J =
7.2 Hz, 1 H), 6.68–6.60 (m, 1 H), 6.55–6.45 (m, 2 H), 6.03 (d, J =
7.8 Hz, 1 H), 4.54 (s, 2 H), 3.12 (d, J = 13.4 Hz, 1 H), 2.91–2.83 (m, 4
H), 2.62 (dd, J = 12.3, 5.5 Hz, 1 H), 2.32 (s, 3 H), 2.29 (s, 3 H), 2.20
(d, J = 5.1 Hz, 1 H), 2.12 (tdd, J = 12.4, 5.8, 4.1 Hz, 2 H), 1.82 (dt, J =
J = 46.3, 15.8 Hz, 1 H), 1.88–1.78 (m, 1 H), 1.70–1.64 (m, 1 H), 1.29
(
(
dt, J = 10.1, 5.7 Hz, 2 H), 1.17 (t, J = 7.1 Hz, 1 H) ppm. 13C NMR
126 MHz, CDCl ): δ = 155.78, 155.63, 149.07, 141.67, 141.51, 132.75,
1
3
12.0, 5.8 Hz, 1 H), 1.46 (qt, J = 12.4, 5.8 Hz, 1 H) ppm. C NMR
3
1
1
1
3
28.80, 128.75, 128.31, 128.20, 127.30, 127.21, 122.07, 121.65,
20.75, 118.58, 118.29, 118.20, 117.95, 113.73, 113.59, 107.52,
07.03, 80.42, 61.46, 45.69, 45.33, 45.19, 44.60, 40.27, 35.70, 35.56,
(126 MHz, CDCl ): δ = 165.61, 159.29, 152.23, 144.29, 133.75, 131.31,
127.65, 127.62, 126.38, 122.16, 120.69, 116.50, 115.47, 110.64,
3
103.26, 96.37, 63.44, 43.81, 40.23, 39.89, 36.66, 31.02, 24.03, 11.49,
+
1.35, 31.12, 26.98, 14.91, 14.67 ppm. HRMS (ESI-TOF): calcd. for 11.08 ppm. HRMS (ESI-TOF): calcd. for C H N O [M + H] 386.2232;
25 27 3
+
C H N O [M + H] 364.2025; found 364.2023.
found 386.2231.
22 25 3 2
6
-Methyl-5,11-dihydro-6H-5a,10b-propanoindolo[2,3-b]quinol-
5-Isopropyl-6-methyl-5,11-dihydro-6H-5a,10b-propano-
indolo[2,3-b]quinoline (4d): The preparation was carried out ac-
cording to the general procedure. Purification by silica gel column
ine (3o): The preparation was carried out according to the general
procedure. Purification by silica gel column chromatography (1 %
ethyl acetate/hexanes) gave 3o (93 % yield) as a white solid. 1
H
chromatography (0.3 % ethyl acetate/hexanes) gave 4d (68 % yield)
1
NMR (500 MHz, CDCl ): δ = 7.06–6.94 (m, 3 H), 6.91 (d, J = 7.2 Hz,
as a white solid. H NMR (500 MHz, CDCl ): δ = 7.09–7.01 (m, 2 H),
3
3
1
6
1
3
5
H), 6.70 (td, J = 7.4, 1.1 Hz, 1 H), 6.64 (dd, J = 7.7, 1.1 Hz, 1 H),
.60–6.55 (m, 1 H), 6.13 (d, J = 7.8 Hz, 1 H), 3.89 (s, 1 H), 3.01 (d, J = 1.0 Hz, 1 H), 6.14 (d, J = 7.7 Hz, 1 H), 4.00 (sept, J = 6.8 Hz, 1 H),
4.1 Hz, 1 H), 2.85 (d, J = 14.1 Hz, 1 H), 2.77 (s, 3 H), 2.16–2.03 (m,
H), 1.90 (ddd, J = 12.4, 8.7, 6.2 Hz, 1 H), 1.79 (tdd, J = 11.6, 6.4,
.1 Hz, 1 H), 1.56 (dtt, J = 12.9, 8.7, 6.6 Hz, 1 H) ppm. 13C NMR
6.99–6.92 (m, 3 H), 6.80 (td, J = 7.1, 1.7 Hz, 1 H), 6.55 (td, J = 7.3,
2.97 (d, J = 13.5 Hz, 1 H), 2.85–2.77 (m, 4 H), 2.25 (ddt, J = 12.6, 5.5,
1.8 Hz, 1 H), 2.09–1.95 (m, 3 H), 1.71 (dtt, J = 11.9, 6.0, 1.7 Hz, 1 H),
13
1.50–1.40 (m, 4 H), 1.20 (d, J = 6.7 Hz, 3 H) ppm. C NMR (126 MHz,
(
126 MHz, CDCl ): δ = 150.89, 144.15, 134.83, 128.20, 127.73, 127.01,
CDCl ): δ = 152.11, 144.86, 135.26, 134.95, 128.14, 127.44, 126.18,
3
3
1
3
26.95, 122.30, 120.05, 116.59, 115.34, 103.91, 91.94, 58.84, 41.88, 123.24, 122.22, 121.64, 116.09, 103.59, 96.92, 63.59, 47.95, 42.59,
9.20, 38.64, 27.55, 23.90 ppm. HRMS (ESI-TOF): calcd. for C H N
40.02, 35.49, 29.52, 25.34, 23.99, 22.34 ppm. HRMS (ESI-TOF): calcd.
19 20 2
+
+
[
M + H] 277.1705; found 277.1704.
for C H N [M + H] 319.2174; found 319.2178.
22 26 2
5
-(4-Methoxybenzyl)-6-methyl-5,11-dihydro-6H-5a,10b-prop-
5-Cyclopentyl-6-methyl-5,11-dihydro-6H-5a,10b-propano-
indolo[2,3-b]quinoline (4e): The preparation was carried out ac-
cording to the general procedure. Purification by silica gel column
anoindolo[2,3-b]quinoline (4a): The preparation was carried out
according to the general procedure. Purification by silica gel column
chromatography (10 % ethyl acetate/hexanes) gave 4a (96 % yield)
chromatography (0.3 % ethyl acetate/hexanes) gave 4e (72 % yield)
1
1
as a white solid. H NMR (500 MHz, CDCl ): δ = 7.31 (d, J = 8.4 Hz,
as a white solid. H NMR (500 MHz, CDCl ): δ = 7.00 (td, J = 7.7,
3
3
Eur. J. Org. Chem. 2017, 2652–2660
www.eurjoc.org
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© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
1
6
.6 Hz, 1 H), 6.96–6.87 (m, 4 H), 6.74 (td, J = 7.3, 1.1 Hz, 1 H), 6.55–
.48 (m, 1 H), 6.11 (d, J = 7.7 Hz, 1 H), 4.12 (p, J = 8.7 Hz, 1 H), 2.94
J = 15.5 Hz, 1 H), 2.25 (s, 3 H), 2.02 (dq, J = 13.2, 2.5 Hz, 1 H), 1.68
(dq, J = 14.2, 3.6, 3.0 Hz, 1 H), 1.55 (ddq, J = 15.3, 7.7, 3.6 Hz, 3 H),
(
(
d, J = 13.4 Hz, 1 H), 2.82 (s, 3 H), 2.76 (d, J = 13.4 Hz, 1 H), 2.28
ddt, J = 12.5, 5.3, 1.7 Hz, 1 H), 2.05–1.84 (m, 5 H), 1.84–1.60 (m, 6
1.42–1.15 (m, 3 H) ppm. 13C NMR (126 MHz, CDCl ): δ = 149.01,
3
139.41, 135.64, 128.17, 127.52, 127.10, 120.89, 120.40, 119.70,
13
H), 1.55 (dq, J = 10.0, 7.4 Hz, 1 H), 1.42–1.33 (m, 1 H) ppm. C NMR 117.74, 116.89, 107.62, 81.73, 41.49, 39.22, 31.81, 27.90, 26.92, 22.29,
(126 MHz, CDCl ): δ = 152.31, 144.93, 135.08, 134.50, 128.12, 127.48,
21.79, 17.28 ppm. HRMS (ESI-TOF): calcd. for C H N [M + H]+
3
21 24 2
1
4
26.03, 122.18, 121.89, 121.04, 116.23, 103.73, 96.81, 63.37, 58.61, 305.2018; found 305.2021.
2.86, 39.79, 35.84, 31.67, 29.95, 29.84, 24.29, 23.83 ppm. HRMS (ESI-
3
,6-Dimethyl-5,11-dihydro-6H-5a,10b-butanoindolo[2,3-b]quin-
+
TOF): calcd. for C H N [M + H] 345.2331; found 345.2332.
24 28 2
oline (4j): The preparation was carried out according to the general
6
-Methyl-5-phenyl-5,11-dihydro-6H-5a,10b-propanoindolo-
procedure. Purification by silica gel column chromatography (1.5 %
ethyl acetate/hexanes) gave 4j (80 % yield) as a white solid. H NMR
1
[2,3-b]quinoline (4f): The preparation was carried out according
to the general procedure. Purification by silica gel column chroma- (500 MHz, CDCl ): δ = 7.14 (t, J = 7.6 Hz, 1 H), 7.09 (d, J = 7.2 Hz, 1
3
tography (0.3 % ethyl acetate/hexanes) gave 4f (86 % yield) as a
H), 6.88 (d, J = 8.0 Hz, 1 H), 6.79 (s, 2 H), 6.54 (d, J = 62.6 Hz, 2 H),
4.02 (s, 1 H), 2.89 (d, J = 15.5 Hz, 1 H), 2.71 (s, 3 H), 2.32 (s, 1 H),
2.23 (s, 3 H), 2.03–1.96 (m, 1 H), 1.66 (s, 1 H), 1.53 (d, J = 11.5 Hz, 3
H), 1.41 (s, 1 H), 1.33–1.18 (m, 2 H) ppm. 13C NMR (126 MHz, CDCl3):
δ = 149.07, 139.32, 135.97, 129.84, 127.85, 126.91, 121.22, 118.03,
1
white solid. H NMR (500 MHz, CDCl ): δ = 7.36 (dd, J = 8.4, 7.2 Hz,
3
2
1
1
1
6
6
H), 7.29–7.23 (m, 2 H), 7.18–7.13 (m, 1 H), 7.08 (dd, J = 7.3, 1.3 Hz,
H), 7.05–6.96 (m, 3 H), 6.83 (t, J = 7.4 Hz, 2 H), 6.61 (t, J = 7.3 Hz,
H), 6.15 (d, J = 7.8 Hz, 1 H), 3.18 (d, J = 13.6 Hz, 1 H), 3.03 (d, J =
3.5 Hz, 1 H), 2.90 (s, 3 H), 2.50–2.42 (m, 1 H), 2.21 (ddt, J = 12.1, 113.26, 107.86, 82.45, 42.20, 39.50, 31.83, 28.49, 27.42, 22.39, 21.83,
+
.1, 1.6 Hz, 1 H), 2.08 (td, J = 12.4, 5.9 Hz, 1 H), 1.96 (td, J = 12.8,
.0 Hz, 1 H), 1.81–1.74 (m, 1 H), 1.52 (dp, J = 19.0, 6.6, 6.2 Hz, 1 H)
20.82 ppm. HRMS (ESI-TOF): calcd. for C H N [M + H] 305.2018;
21 24 2
found 305.2019.
13
ppm. C NMR (126 MHz, CDCl ): δ = 152.20, 146.86, 146.58, 133.75,
3
Ethyl 4,6-Dimethyl-5,11-dihydro-6H-10b,5a-(ethanoiminometh-
ano)indolo[2,3-b]quinoline-14-carboxylate (4k): The preparation
was carried out according to the general procedure. Purification by
1
1
2
33.42, 128.80, 127.90, 127.69, 127.11, 126.31, 123.20, 122.34,
22.17, 116.13, 103.34, 95.65, 65.55, 42.60, 40.44, 37.61, 29.53,
+
4.37 ppm. HRMS (ESI-TOF): calcd. for C H N [M + H] 353.2018;
2
5 24 2
silica gel column chromatography (10 % ethyl acetate/hexanes)
found 353.2016.
1
gave 4k (73 % yield) as a white solid. H NMR (500 MHz, CDCl ): δ =
3
3
,6-Dimethyl-5,11-dihydro-6H-5a,10b-propanoindolo[2,3-b]-
7.17 (dd, J = 34.0, 7.2 Hz, 1 H), 7.10 (t, J = 7.7 Hz, 1 H), 6.95 (d, J =
quinoline (4g): The preparation was carried out according to the 7.6 Hz, 1 H), 6.84 (d, J = 7.4 Hz, 1 H), 6.72 (t, J = 7.4 Hz, 1 H), 6.62
general procedure. Purification by silica gel column chromatogra- (t, J = 7.4 Hz, 1 H), 6.39 (dd, J = 13.2, 7.6 Hz, 1 H), 4.28–4.01 (m, 4
phy (1.3 % ethyl acetate/hexanes) gave 4g (97 % yield) as a white
H), 3.98–3.72 (m, 1 H), 3.20–2.90 (m, 3 H), 2.73 (s, 3 H), 2.59 (dd, J =
47.7, 15.7 Hz, 1 H), 2.22 (s, 3 H), 1.89 (ddt, J = 15.0, 11.1, 4.7 Hz, 1
H), 1.79–1.70 (m, 1 H), 1.25 (dt, J = 66.1, 7.1 Hz, 3 H) ppm. C NMR
1
solid. H NMR (500 MHz, CDCl ): δ = 7.05 (dd, J = 7.2, 1.2 Hz, 1 H),
3
1
3
6
.99 (td, J = 7.6, 1.3 Hz, 1 H), 6.82 (dd, J = 7.9, 1.9 Hz, 1 H), 6.75 (d,
J = 1.9 Hz, 1 H), 6.14 (d, J = 7.7 Hz, 1 H), 4.40 (s, 1 H), 3.00 (d, J =
(126 MHz, CDCl ): δ = 155.74, 155.58, 149.07, 139.58, 139.35, 132.73,
3
1
2
4.0 Hz, 1 H), 2.84 (d, J = 14.1 Hz, 1 H), 2.78 (s, 3 H), 2.19 (s, 3 H),
.17–2.06 (m, 3 H), 1.94–1.87 (m, 1 H), 1.81 (dp, J = 11.5, 5.7 Hz, 1
128.43, 128.24, 128.12, 126.64, 122.02, 121.63, 121.15, 120.32,
118.00, 117.90, 117.73, 107.40, 106.81, 80.41, 61.40, 45.76, 45.37,
1
3
H), 1.57 (dddd, J = 15.3, 12.8, 8.6, 6.5 Hz, 1 H) ppm. C NMR 45.19, 44.57, 40.29, 35.80, 35.66, 31.58, 31.35, 26.84, 17.11, 14.88,
(126 MHz, CDCl ): δ = 151.03, 141.81, 134.85, 129.04, 128.91, 127.65,
14.66 ppm. HRMS (ESI-TOF): calcd. for C23H27N O [M + H]+
3
3
2
1
3
27.35, 127.01, 122.28, 116.30, 115.12, 103.62, 91.94, 59.03, 42.21, 378.2182; found 378.2183.
9.35, 38.74, 27.37, 23.91, 20.76 ppm. HRMS (ESI-TOF): calcd. for
Ethyl 4-Chloro-6-methyl-5,11-dihydro-6H-10b,5a-(ethanoimino-
methano)indolo[2,3-b]quinoline-14-carboxylate (4l): The prepa-
ration was carried out according to the general procedure. Purifica-
tion by silica gel column chromatography (10 % ethyl acetate/hex-
anes) gave 4l (69 % yield) as a white solid. 1H NMR (500 MHz,
+
C H N [M + H] 291.1861; found 291.1867.
20 22 2
4
-Chloro-6-methyl-5,11-dihydro-6H-5a,10b-propanoindolo-
[2,3-b]quinoline (4h): The preparation was carried out according
to the general procedure. Purification by silica gel column chroma-
tography (0.3 % ethyl acetate/hexanes) gave 4h (84 % yield) as a
CDCl ): δ = 7.22–7.04 (m, 3 H), 6.85 (d, J = 7.4 Hz, 1 H), 6.71 (q, J =
3
1
white solid. H NMR (500 MHz, CDCl ): δ = 7.07 (d, J = 8.0 Hz, 1 H),
8.0, 7.5 Hz, 1 H), 6.59 (t, J = 7.7 Hz, 1 H), 6.41 (d, J = 7.8 Hz, 1 H),
4.84 (s, 1 H), 4.22–3.99 (m, 3 H), 3.93–3.70 (m, 1 H), 3.24–2.97 (m, 2
H), 2.93 (d, J = 15.7 Hz, 1 H), 2.74 (s, 3 H), 2.62 (dd, J = 48.6, 15.8 Hz,
3
7
2
.01 (dd, J = 7.3, 1.3 Hz, 1 H), 6.80 (d, J = 7.3 Hz, 1 H), 6.63–6.53 (m,
H), 6.13 (d, J = 7.7 Hz, 1 H), 5.18 (s, 1 H), 3.10 (d, J = 14.1 Hz, 1
1
3
H), 2.84 (d, J = 14.1 Hz, 1 H), 2.80 (s, 3 H), 2.19 (dq, J = 10.4, 5.3,
.7 Hz, 1 H), 2.16–2.08 (m, 2 H), 2.00 (ddd, J = 12.4, 8.8, 6.2 Hz, 1
H), 1.84 (tq, J = 11.5, 5.5 Hz, 1 H), 1.61 (dddd, J = 15.3, 12.8, 8.7,
1 H), 1.99–1.78 (m, 2 H), 1.24 (dt, J = 59.0, 7.1 Hz, 3 H) ppm.
C
4
NMR (126 MHz, CDCl ): δ = 155.80, 155.52, 148.90, 138.03, 137.84,
3
132.14, 128.49, 127.14, 127.07, 127.00, 123.54, 122.74, 122.18,
6
1
1
.6 Hz, 1 H) ppm. 13C NMR (126 MHz, CDCl ): δ = 150.88, 140.76, 121.75, 118.68, 118.32, 118.21, 118.10, 107.62, 80.75, 80.57, 61.46,
34.15, 128.74, 127.83, 126.82, 126.50, 122.26, 119.97, 119.80,
3
46.45, 45.59, 45.47, 45.28, 40.20, 35.65, 31.50, 31.13, 27.05, 14.88,
16.57, 103.83, 91.99, 59.05, 42.36, 39.61, 38.78, 27.28, 23.96 ppm.
14.67 ppm. HRMS (ESI-TOF): calcd. for C22H24ClN O2 [M + H]+
3
+
HRMS (ESI-TOF): calcd. for C19H19ClN [M + H] 311.1315; found
398.1635; found 398.1637.
2
3
11.1309.
(
5aR,10bS,11R)-6-Methyl-11-phenyl-5,11-dihydro-6H-5a,10b-
4,6-Dimethyl-5,11-dihydro-6H-5a,10b-butanoindolo[2,3-b]quin- butanoindolo[2,3-b]quinoline (6a): A mixture of 9-methyl-2,3,4,9-
oline (4i): The preparation was carried out according to the general
tetrahydro-1H-carbazole (1a; 1.85 g, 10.0 mmol, 2.0 equiv.),
procedure. Purification by silica gel column chromatography (0.3 % 2-aminobenzyl alcohol 5 (1.0 g, 5.0 mmol, 1.0 equiv.), molecular
1
ethyl acetate/hexanes) gave 4i (83 % yield) as a white solid. H NMR
500 MHz, CDCl ): δ = 7.15 (td, J = 7.6, 1.3 Hz, 1 H), 7.11 (dd, J =
7
6
1
sieves (4 Å; 1.0 g), and In(OTf) (280 mg, 10 mol-%) in 1,2-dichloro-
3
(
ethane (50 mL) was stirred at 50 °C for 24 h. Upon completion of
the reaction, the mixture was cooled to room temperature. The
organic layer was separated and washed with an aqueous NaHCO3
solution. The aqueous layer was extracted with dichloromethane
3
.3, 1.2 Hz, 1 H), 6.99 (d, J = 7.3 Hz, 1 H), 6.89 (d, J = 7.4 Hz, 1 H),
.78 (t, J = 7.3 Hz, 1 H), 6.63 (t, J = 7.4 Hz, 1 H), 6.47 (d, J = 7.7 Hz,
H), 3.89 (s, 1 H), 2.96 (d, J = 15.5 Hz, 1 H), 2.73 (s, 3 H), 2.36 (d,
Eur. J. Org. Chem. 2017, 2652–2660
www.eurjoc.org
2658
© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
(
3 ×). The combined organic layers were washed with brine and
J. Knölker, K. R. Reddy, Chem. Rev. 2002, 102, 4303; d) C. Marti, E. M.
Carreira, Eur. J. Org. Chem. 2003, 12, 2209; e) A. W. Schmidt, K. R. Reddy,
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J. Org. Chem. 2002, 67, 7124; b) J. R. Fuchs, R. L. Funk, J. Am. Chem. Soc.
dried with anhydrous Na SO . After filtration, the solution was con-
centrated. The remaining residue was purified by column chroma-
tography on silica gel (ethyl acetate and hexanes) to afford 6a
2
4
[
1
(1.76 g, 96 %) as a white solid. H NMR (500 MHz, CDCl ): δ = 7.13
3
(s, 5 H), 6.95 (t, J = 7.5 Hz, 1 H), 6.90 (d, J = 7.6 Hz, 1 H), 6.81 (t, J =
2004, 126, 5068; c) H. Wu, F. Xue, X. Xiao, Y. Qin, J. Am. Chem. Soc. 2010,
7
6
.6 Hz, 1 H), 6.60 (dt, J = 15.0, 7.5 Hz, 2 H), 6.27 (t, J = 7.4 Hz, 1 H),
.17 (d, J = 7.2 Hz, 1 H), 5.94 (d, J = 7.9 Hz, 1 H), 4.55 (s, 1 H), 3.96
1
32, 14052; d) H. Zhang, L. Hong, H. Kang, R. Wang, J. Am. Chem. Soc.
2013, 135, 14098; e) S. J. Han, F. Vogt, S. Krishnan, J. A. May, M. Gatti,
S. C. Virgil, B. M. Stoltz, Org. Lett. 2014, 16, 3316; f) S. J. Han, F. Vogt, J. A.
May, S. Krishnan, M. Gatti, S. C. Virgil, B. M. Stoltz, J. Org. Chem. 2015,
(s, 1 H), 2.59 (s, 3 H), 2.18 (dt, J = 12.6, 7.4 Hz, 1 H), 2.05 (dt, J =
1
2.8, 6.6 Hz, 1 H), 1.90 (dt, J = 12.3, 6.0 Hz, 1 H), 1.81 (dt, J = 12.7,
.8 Hz, 1 H), 1.74 (dp, J = 12.6, 6.3 Hz, 1 H), 1.42–1.31 (m, 1 H) ppm.
8
0, 528; g) B. M. Trost, M. Osipov, Chem. Eur. J. 2015, 21, 16318; h) B. M.
6
1
3
Trost, M. Osipov, S. Krüger, Y. Zhang, Chem. Sci. 2015, 6, 349.
C NMR (126 MHz, CDCl ): δ = 151.22, 144.23, 138.29, 131.95,
3
[
3] a) A. Numata, C. Takahashi, Y. Ito, T. Takada, K. Kawai, Y. Usami, E. Matsu-
mura, M. Imachi, T. Ito, Y. Hasegawa, Tetrahedron Lett. 1993, 34, 2355;
b) R. Jadulco, R. A. Edrada, R. Ebel, A. Berg, K. Schaumann, V. Wray, K.
Steube, P. Proksch, J. Nat. Prod. 2004, 67, 78; c) H. Hayashi, H. Matsumoto,
K. Akiyama, Biosci. Biotechnol. Biochem. 2004, 68, 753; d) P. W. Dalsgaard,
J. W. Blunt, M. H. G. Munro, J. C. Frisvad, C. Christophersen, J. Nat. Prod.
1
1
2
3
31.58, 128.72, 128.00, 127.85, 127.14, 127.04, 126.72, 126.38,
19.96, 115.62, 115.50, 103.92, 92.29, 63.19, 53.83, 42.37, 38.45,
+
7.77, 23.86 ppm. HRMS (ESI-TOF): calcd. for C H N [M + H]
2
5 24 2
53.2018; found 353.2019.
Retro-[4+2]-Cycloaddition Reaction of 3a: A mixture of 6-methyl-
5
5
stirred at 80 °C for 12 h. Upon completion of the reaction, the mix-
ture was cooled to room temperature. The organic layer was sepa-
rated and washed with an aqueous NaHCO solution. The aqueous
2005, 68, 258.
,11-dihydro-6H-5a,10b-butanoindolo[2,3-b]quinoline (3a; 1.45 g,
.0 mmol) and In(OTf)3 (140 mg, 10 mol-%) in DCE (25 mL) was
[
4] a) G. Subramaniam, O. Hiraku, M. Hayashi, T. Koyano, K. Komiyama, T. S.
Kam, J. Nat. Prod. 2007, 70, 1783; b) M. Zhang, X.-P. Huang, L.-Q. Shen,
Y. Qin, J. Am. Chem. Soc. 2009, 131, 6013; c) W.-W. Zi, W.-Q. Xie, D.-W. Ma,
J. Am. Chem. Soc. 2012, 134, 9126; d) B. D. Horning, D. W. MacMillan, J.
Am. Chem. Soc. 2013, 135, 6442.
3
layer was extracted with dichloromethane (DCM; 3 ×). The com-
bined organic layers were washed with brine and dried with anhy-
drous Na SO . After filtration, the solution was concentrated. The
remaining residue was purified by column chromatography on silica
gel (ethyl acetate and hexanes) to afford various fractions, which
were collected and characterized as 1a (24 % yield), 7 (14 % yield),
[5] For selected examples, see: a) Q. Cai, S.-L. You, Org. Lett. 2012, 14, 3040;
b) R. E. Ziegler, S.-J. Tan, T.-S. Kam, J. A. Porco Jr., Angew. Chem. Int. Ed.
2012, 51, 9348; Angew. Chem. 2012, 124, 9482; c) Y.-C. Zhang, J.-J. Zhao,
F. Jiang, S.-B. Sun, F. Shi, Angew. Chem. Int. Ed. 2014, 53, 13912; Angew.
Chem. 2014, 126, 14132; d) V. Ramella, Z.-H. He, C. G. Daniliuc, A. Studer,
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2
4
1
8, 628; f) R.-D. Gao, Q.-L. Xu, B. Zhang, Y.-T. Gu, L.-X. Dai, S.-L. You, Chem.
and 8 (18 % yield). Data for 2-[(9-methyl-2,3,4,9-tetrahydro-1H-car-
Eur. J. 2016, 22, 11601.
1
bazol-6-yl)methyl]aniline (7): H NMR (500 MHz, CDCl ): δ = 7.34 (d,
3
[
6] a) For reviews, see: R. W. Van DeWater, T. R. R. Pettus, Tetrahedron 2002,
J = 1.6 Hz, 1 H), 7.19 (d, J = 8.3 Hz, 1 H), 7.12 (ddd, J = 17.9, 7.5,
5
8, 5367; b) C. M. Beaudry, J. P. Malerich, D. Trauner, Chem. Rev. 2005,
1
1
.5 Hz, 2 H), 7.00 (dd, J = 8.4, 1.7 Hz, 1 H), 6.80 (td, J = 7.4, 1.2 Hz,
H), 6.67 (dd, J = 7.8, 1.2 Hz, 1 H), 4.04 (s, 2 H), 3.61 (s, 4 H), 3.57
105, 4757; c) D. Richter, N. Hampel, T. Singer, A. R. Ofial, H. Mayr, Eur. J.
Org. Chem. 2009, 19, 3203; d) S. E. Rokita (Ed.), Quinone Methides, Wiley,
New York, 2009; e) T. P. Pathak, M. S. Sigman, J. Org. Chem. 2011, 76,
9210; f) N. J. Willis, C. D. Bray, Chem. Eur. J. 2012, 18, 9160; g) M. S. Singh,
A. Nagaraju, N. Anand, S. Chowdhury, RSC Adv. 2014, 4, 55924.
(
s, 1 H), 2.71 (q, J = 7.0 Hz, 4 H), 1.96 (qd, J = 7.6, 6.2, 4.0 Hz, 2 H),
1
3
1
1
1
2
.90–1.83 (m, 2 H) ppm. C NMR (126 MHz, CDCl ): δ = 145.07,
3
36.31, 135.74, 130.88, 129.39, 127.49, 127.38, 126.77, 121.46,
18.61, 117.52, 115.90, 109.04, 108.81, 38.71, 29.13, 23.32, 22.23,
[
[
7] For reviews, see: a) K. Wojciechowski, Eur. J. Org. Chem. 2001, 19, 3587;
b) A. A. Jaworski, K. A. Scheidt, J. Org. Chem. 2016, 81, 10145.
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Chem. 1999, 111, 2054; b) H. Steinhagen, E. J. Corey, Org. Lett. 1999, 1,
+
1.22 ppm. HRMS (ESI-TOF): calcd. for C H N [M + H] 291.1861;
2
0 22 2
found 291.1864. Data for 2-[(9-methyl-2,3,4,9-tetrahydro-1H-carb-
1
azol-8-yl)methyl]aniline (8): H NMR (500 MHz, CDCl ): δ = 7.43 (d,
3
8
23.
J = 8.0 Hz, 1 H), 7.17–7.08 (m, 3 H), 6.97 (dd, J = 8.0, 1.5 Hz, 1 H),
[
9] a) Q.-Q. Yang, C. Xiao, L.-Q. Lu, J. An, F. Tan, B.-J. Li, W.-J. Xiao, Angew.
Chem. Int. Ed. 2012, 51, 9137; Angew. Chem. 2012, 124, 9271; b) Q.-Q.
Yang, Q. Wang, J. An, J.-R. Chen, L.-Q. Lu, W.-J. Xiao, Chem. Eur. J. 2013,
19, 8401; c) H. Huang, Y. Yang, X. Zhang, W. Zeng, Y. Liang, Tetrahedron
Lett. 2013, 54, 6049.
6
2
1
.81 (td, J = 7.4, 1.3 Hz, 1 H), 6.68 (dd, J = 7.8, 1.2 Hz, 1 H), 4.07 (s,
H), 3.57 (s, 5 H), 2.73 (dt, J = 12.6, 6.2 Hz, 4 H), 2.01–1.94 (m, 2 H),
1
3
.92–1.85 (m, 2 H) ppm. C NMR (126 MHz, CDCl ): δ = 145.07,
3
1
1
2
37.23, 135.80, 131.76, 130.91, 127.47, 126.50, 125.93, 119.78,
18.65, 117.98, 115.92, 109.17, 108.44, 38.99, 29.08, 23.33, 22.18,
[
[
10] a) M. T. Hovey, C. T. Check, A. F. Sipher, K. A. Scheidt, Angew. Chem. Int.
Ed. 2014, 53, 9603; Angew. Chem. 2014, 126, 9757; b) A. Lee, A. Younai,
C. K. Price, J. Izquierdo, R. K. Mishra, K. A. Scheidt, J. Am. Chem. Soc. 2014,
+
1.19 ppm. HRMS (ESI-TOF): calcd. for C H N [M + H] 291.1861;
2
0 22 2
found 291.1863.
1
36, 10589.
11] a) R. D. Bowen, D. E. Davies, C. W. G. Fishwick, T. O. Glasbey, S. J. Noyce,
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Acknowledgments
This study was financially supported by the National Natural
Science Foundation of China (21202100, 81502985) and The
Strategic Priority Research Program of the Chinese Academy of
Sciences (XDA01040302).
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