Azocinoindole synthesis by a gold(I)-catalyzed ring expansion of 2-propargyl-β-tetrahydrocarboline

Article abstract of DOI:10.1002/chem.201304524

A new methodology taking advantage of gold(I)-catalyzed ring expansion has been developed to assemble tricyclic 1H-azocino[5,4-b]indoles from 2-propargyl-β-tetrahydrocarbolines. The azocinoindoles were obtained in moderate to excellent yields; the structure of which was established by X-ray crystallographic analysis. A mechanism involving regioselective intramolecular hydroarylation, [1,2]-alkenyl migration and carbon-carbon bond-fragmentation was proposed. Route to ring expansion: A new methodology taking advantage of gold(I)-catalyzed ring expansion has been developed to assemble tricyclic 1H-azocino[5,4-b]indoles from 2-propargyl-β-tetrahydrocarbolines (see scheme; EWG= electron-withdrawing group). A mechanism involving regioselective hydroarylation, [1,2]-alkenyl migration, and carbon-carbon bond fragmentation was proposed.

Full text of DOI:10.1002/chem.201304524

DOI: 10.1002/chem.201304524
Full Paper
&
Ring Expansion
Azocinoindole Synthesis by a Gold(I)-Catalyzed Ring Expansion of
2-Propargyl-b-Tetrahydrocarboline
Lei Zhang,[a] Lina Chang,[a] Hongwen Hu,[a] Huaqin Wang,[b] Zhu-Jun Yao,[a] and
Shaozhong Wang*[a]
Abstract: A new methodology taking advantage of gold(I)-
catalyzed ring expansion has been developed to assemble
tricyclic 1H-azocino[5,4-b]indoles from 2-propargyl-b-tetrahy-
drocarbolines. The azocinoindoles were obtained in moder-
ate to excellent yields; the structure of which was estab-
lished by X-ray crystallographic analysis. A mechanism in-
volving regioselective intramolecular hydroarylation, [1,2]-al-
kenyl migration and carbon–carbon bond-fragmentation
was proposed.
Introduction
Heteroannulated azocine derivatives belong to a kind of com-
pounds containing an eight-membered ring.[1] As a member of
heteroannulated azocine, azocinoindole features a fusion of
indole and azocine rings. The tricyclic heterocycle has attracted
much attention from the chemical community because
a number of naturally occurring alkaloids possess the fragment
in their structures. For instance, as the skeleton core of penta-
and hexacyclic alkaloids okaramine,[2] grandilodine,[3] and lun-
durine,[4] 1H-azocino[5,4-b]indole became a common target for
different research groups (Scheme 1).
Hence, diverse methodologies have been developed for the
assembly of 1H-azocino[5,4-b]indole scaffold, which was de-
signed as a key intermediate to polycyclic indole alkaloids
(Scheme 2). An elegant example, taking advantage of transi-
Scheme 2. Transition-metal catalysis in 1H-azocino[5,4-b]indole assembly.
tion-metal catalysis, was initially reported by Corey in 2002, in
which an amide-protected N-prenyl-(S)-tryptophan methyl
ester was employed as substrate and stoichiometric amount of
palladium acetate was utilized as the catalyst.[5] A mechanistic
study demonstrated that the cyclization is triggered by CÀH
activation at C2 position of the indole ring and the presence
of methyl ester proved to be essential for the transformation.
In 2006, based on the alkynophilic property of gold catalysts,
Echavarren advanced a 8-endo-dig cycloisomerization to obtain
1H-azocino[5,4-b]indoles from N-propargyl-substituted trypt-
amine and tryptophan ester.[6] However, in the case of sub-
strates tethered with internal alkynes, the transformation was
contaminated by a competitive 7-exo-dig cycloisomerization as
a side reaction. Furthermore, when one-valent cationic gold
complex was employed in place of [AuCl3], 7-exo-dig cyclo-
Scheme 1. 1H-Azocino[5,4-b]indole alkaloids.
[a] L. Zhang, L. Chang, Prof. H. Hu, Prof. Dr. Z.-J. Yao, Prof. Dr. S. Wang
State key Laboratory of Coordination Chemistry
School of Chemistry and Chemical Engineering
Nanjing University, Nanjing 210093 (P.R. China)
E-mail: wangsz@nju.edu.cn
[b] H. Wang
Modern Analytical Center of Nanjing University
Nanjing 210093 (P.R. China)
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201304524.
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isomerization became a major reaction. Although Van der
Eycken partially improved the 8-endo-dig cycloisomerization by
switching the substrate to propiolamide, limitations in terms of
substrate scope and generality of the transformation still
exist.[7] Aiming at addressing the problem, we present a con-
ceptually new strategy for the construction of 1H-azocino[5,4-
b]indole by a gold(I)-catalyzed ring expansion of 2-propargyl-b-
tetrahydrocarboline, which features a carbon–carbon bond
fragmentation.[8,9]
Table 1. Screened conditions for the AuI-catalyzed ring expansion of 2-
propargyl-b-tetrahydrocarboline.[a]
Entry Substrate Conditions
Product
(yield [%])[c]
1[b]
2[b]
3[b]
4[b]
1a
1a
1a
1a
10 mol% [AuNTf2(PPh3)], CH2Cl2,
RT, 12 h; then boron reduction
10 mol% [AuNTf2(PPh3)], 1.0 equiv TFA,
CH2Cl2, RT, 2 h; then boron reduction
2a (24);
3 (11)
2a (46);
3 (38)
Results and Discussion
We started the investigation by designing compounds 1a,b as
model substrates, which were prepared by selective propargy-
lation of the same b-tetrahydrocarboline, a Pictet–Spengler re-
action product of tryptamine and methyl propiolate.[10,11] When
10 mol% [AuNTf2(PPh3)] (NTf2 =bis-{(trifluoromethyl)sulfonyl}-
imide) was used as catalyst, complete conversion of 2-proparg-
yl-b-tetrahydrocarboline 1a was observed in CH2Cl2 after 12 h
at room temperature. To our disappointment, we could not
obtain any pure product at the beginning because partial de-
composition of products always occurred during the work-up.
After a thorough analysis of the crude spectra, we deduced
that new functional groups such as alkene and enamino ester
should be generated during the process. Therefore, to access
a stable product, we envisioned a two-step protocol consisting
of gold catalysis and subsequent chemoselective reduction of
the enamine motif. When the gold(I)-catalyzed reaction was
finished, the boron reductant NaBH(OAc)3 and excess acetic
acid were added in a one-pot manner (Table 1). Eventually, two
products were isolated nearly at a 2:1 ratio, which were identi-
fied as 1H-azocino[5,4-b]indole 2a and azepino[4,5-b]indole 3,
respectively (Table 1, entry 1). In the presence of acidic addi-
tives such as trifluoroacetic acid (TFA) and acetic acid, the
gold(I)-catalyzed process can be accelerated and the product
yields were improved, however, the ratio of 2a and 3 was
almost 1:1 (Table 1, entries 2 and 3). When toluene was used as
solvent, similar acceleration and product distribution were ob-
served in the absence of acids (Table 1, entry 4). Switching the
catalyst from [AuNTf2(PPh3)] to [AuCl3] led to the formation of
a messy mixture, even though the starting material disap-
peared in 2 h (Table 1, entry 5). To our delight, when substrate
1b bearing an ethyl substituent at the alkyne terminus was
tested, the gold-catalyzed ring expansion proceeded cleanly,
delivering 1H-azocino[5,4-b]indole 2b in excellent yield either
in dichloromethane or in toluene (Table 1, entries 6 and 7). Of
note is that none of the alternative regioisomer of 2b was de-
tected. The attached ethyl group makes the 1H-azocino[5,4-
b]indole substantially stable, thus making further reduction un-
necessary, and also enhances the regioselectivity of the trans-
formation. Further optimization revealed that even when the
amount of gold catalyst was reduced as low as 1 mol%, the
ring expansion reaction can still be carried out efficiently,
albeit at elevated temperature (Table 1, entry 8).
10 mol% [AuNTf2(PPh3)], 1.0 equiv HOAc, 2a (46);
CH2Cl2, RT, 2 h; then boron reduction
10 mol% [AuNTf2(PPh3)], PhMe,
RT, 2 h; then boron reduction
10 mol% [AuCl3], CH2Cl2, RT, 2 h
10 mol% [AuNTf2(PPh3)], CH2Cl2,
RT, 12 h
10 mol% [AuNTf2(PPh3)], PhMe,
RT, 2 h
1 mol% [AuNTf2(PPh3)], PhMe,
110 8C, 2 h
3 (45)
2a (38);
3 (34)
[d]
5
6
1a
1b
–
2b (83)
2b (81)
2b (92)
7
8
1b
1b
[a] The concentration is 0.1m. [b] Reduction conditions: 2.0 equiv NaBH-
(OAc)3, 20 equiv HOAc, RT, 1 h. [c] Yield of the isolated product after
column chromatography. [d] Could not be determined due to the forma-
tion of a messy mixture.
and aryl groups (Ph, 4-MeOPh, 4-NO2Ph) appended on the
alkyne tethers participated in the gold-catalyzed ring expan-
sion smoothly, affording the expected 1H-azocino[5,4-b]indoles
in good to excellent yields (Table 2, entries 1–5). The structure
of 1H-azocino[5,4-b]indole 2e was unambiguously confirmed
by using X-ray crystallographic analysis (Figure 1, top).[12] It ap-
pears that the attached phenyl groups favor the conversion
and the electronic effect of the substituents on the benzene
moiety is not significant. However, the electronic nature of the
substituents on the nitrogen atom of the indole core is critical
as both electron-donating groups (Bn, Me) gave the products
in an average yield up to 90%, whereas electron-withdrawing
group (Ts) inhibited the reaction (Table 2, entries 6 and 7). A va-
riety of substituents (Cl, Me, MeO) at position C6 of b-tetrahy-
drocarboline skeleton were well-tolerated, and the 10-me-
thoxy-1H-azocino[5,4-b]indole 2l was isolated in a nearly quan-
titative yield (Table 2, entry 8). Furthermore, the presence of
methoxycarbonyl group at position C3 of b-tetrahydrocarbo-
line 1m derived from l-tryptophan did not interfere with the
process, giving access to 2m perfectly (Table 2, entry 9). The
structure of 2m was further confirmed by X-ray crystallograph-
ic analysis (Figure 1, bottom). To ascertain whether the me-
thoxycarbonyl group at position C1 of b-tetrahydrocarboline is
essential or not, b-tetrahydrocarboline 1n containing a phe-
none unit in lieu of the ester was subjected to identical condi-
tions, 1H-azocino[5,4-b]indole 2n was achieved in relatively
lower yield after exhaustive reduction (Table 2, entry 10). On
the contrary, the ring expansion did not take place when the
Under the optimized conditions, the generality of the trans-
formation was next evaluated. As well as b-tetrahydrocarboline
1b, substrates 1c–g containing alkyl (silyloxymethyl, n-pentyl)
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acetate moiety was replaced by
Table 2. AuI-catalyzed ring expansion of 2-propargyl-b-tetrahydrocarboline.[a]
either an alkyl or
group.
a phenyl
Entry
2-propargyl-b-
1H-azocino[5,4-b]indole
Yield
[%][c]
tetrahydrocarboline
To account for this phenom-
enon, plausible mechanism
a
was proposed as outlined in
Scheme 3. The selective coordi-
nation between the carbon–
carbon triple bond and carbo-
philic gold(I) catalyst results in
an intramolecular nucleophilic
attack by b-tetrahydrocarboline.
Then, a dearomatized spiro inter-
mediate I is generated, which
can be transformed to carbocat-
ion II through a preferable [1,2]-
alkenyl migration. The benign
electron donation of a nitrogen
atom at the g position of carbo-
cation induces the rupture of
CaÀCb sigma bond, which is rem-
iniscent of a cationic Grob frag-
mentation.[13] Subsequently, the
obtained iminium III isomerizes
to enamino ester IV by losing
a proton. The presence of ace-
tate group at C1 position of b-
tetrahydrocarboline might pro-
mote the isomerization from imi-
nium to enamine, which, in com-
bination with a subsequent pro-
todeauration, facilitates an irre-
versible ring expansion. After the
protonolysis of the CÀAu bond,
the 1H-azocino[5,4-b]indole is
formed.
1[b]
71
80
92
88
87
90
2
3
4
5
6
7
8
91
Conclusion
A conceptually new approach
has been developed to assemble
tricyclic 1H-azocino[5,4-b]indoles
from 2-propargyl-b-tetrahydro-
carbolines by means of a gold-
catalyzed ring expansion. The
protocol features mild condi-
tions and benign group toler-
ance, as well as high catalytic ef-
ficiency, which is complementary
to the current methodologies.
Further extensions of the ring
expansion will be disclosed in
due course.
1j: R=Cl
1k: R=Me
1l: R=OMe
2j: R=Cl
2k: R=Me
2l: R=OMe
87
92
98
9
95
45
10[b]
[a] Reaction conditions: 1 mol% [AuNTf2(PPh3)], toluene, 1108C, 2 h. [b] Reduction conditions used as shown in
Table 1. [c] Yield of the isolated product after column chromatography.
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Experimental Section
All melting points were determined without correction. 1H NMR
spectra were obtained at 300 or 400 MHz, and 13C NMR spectra
were obtained at 75 or 100 MHz. Spectra were recorded in CDCl3
or [D6]DMSO solution using the residual protonated solvent as the
internal standards, J values are given in Hz.
General procedure for the preparation of 2-propargyl-b-
tetrahydrocarboline 1a–n
A
solution of methyl propiolate (25.0 mmol) and tryptamine
(25.0 mmol) in THF (50 mL) was stirred at room temperature for
6 h. The reaction mixture was concentrated under reduced pres-
sure. Then, the obtained solid was dissolved in anhydrous dichloro-
methane (50 mL), and the formed solution was cooled to 08C. Tri-
fluoroacetic acid (50.0 mmol) was added dropwise in 15 min. After
the addition, the mixture was stirred at 08C for another 1 h. The re-
action mixture was washed with saturated Na2CO3 solution (50 mL)
and water (50 mL) successively. The organic layer was dried with
anhydrous Na2SO4, filtered, and concentrated. The residue was pu-
rified by flash chromatography (CH2Cl2/MeOH as eluent) to give 2-
unsubstituted b-tetrahydrocarboline.
An oven-dried flask was charged with 2-unsubstituted b-tetrahy-
drocarboline (2.0 mmol), propargyl mesylate (2.0 mmol) and anhy-
drous K2CO3 (8.0 mmol). Dry acetonitrile (10 mL) was added and
the resultant mixture was allowed to heat and stirred at 708C for
4 h. The reaction mixture was cooled to room temperature and
excess K2CO3 was filtered off. After the removal of solvent under re-
duced pressure, the crude product was purified by flash chroma-
tography (petroleum ether/ethyl acetate (PE/EA) as eluent) to pro-
vide 2-propargyl-b-tetrahydrocarboline.
Figure 1. X-ray structure of azocinoindole 2e·CHCl3 (top) and 2m (bottom).
Methyl
2-(2-(prop-2-ynyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-
b]indol-1-yl)acetate (1a): Oil. Rf (PE/EtOAc, 2:1)=0.70; 1H NMR
(300 MHz, CDCl3): d=8.56 (brs, 1H), 7.49 (d, J=7.7 Hz, 1H), 7.33 (d,
J=7.9 Hz, 1H), 7.16 (td, J1 =7.7, J2 =1.2 Hz, 1H), 7.09 (td, J1 =7.8,
J2 =1.2 Hz, 1H), 4.42 (dd, J1 =9.9, J2 =3.3 Hz, 1H), 3.76 (s, 3H),
3.60–3.47 (m, 2H), 3.26–3.08 (m, 2H), 3.02 (dd, J1 =17.1, J2 =3.6 Hz,
1H), 2.94–2.76 (m, 2H), 2.67 (dt, J1 =15.8, J2 =4.4 Hz, 1H), 2.27 ppm
(t, J=2.4 Hz, 1H); 13C NMR (75 MHz, CDCl3): d=173.9, 135.9, 133.6,
126.9, 121.9, 119.4, 118.3, 111.1, 107.6, 80.2, 73.0, 52.7, 52.1, 45.6,
42.7, 39.8, 18.2 ppm; IR (KBr) n˜ =3401, 3287, 2950, 1728, 1437,
1171, 745 cmÀ1; HRMS (ESI) m/z calcd for C17H19N2O2: 283.1447
[M+H]+; found: 283.1444.
Methyl
2-(2-(pent-2-ynyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-
b]indol-1-yl)acetate (1b): Yellow solid. M.p. 92–948C; Rf (PE/EtOAc,
1
2:1)=0.64; H NMR (300 MHz, CDCl3): d=8.57 (brs, 1H), 7.49 (d, J=
7.5 Hz, 1H), 7.32 (d, J=7.9 Hz, 1H), 7.15 (t, J=7.3 Hz, 1H), 7.08 (t,
J=7.2 Hz, 1H), 4.40 (d, J=7.5 Hz, 1H), 3.76 (s, 3H), 3.56–3.44 (m,
2H), 3.30–2.95 (m, 3H), 2.95–2.73 (m, 2H), 2.73–2.59 (m, 1H), 2.21
(qt, J1 =7.5 Hz, J2 =2.1 Hz, 2H), 1.13 ppm (t, J=7.5 Hz, 3H);
13C NMR (75 MHz, CDCl3): d=174.0, 135.6, 133.8, 126.7, 121.6,
119.1, 118.0, 110.9, 107.5, 86.5, 74.9, 52.4, 51.9, 45.5, 43.0, 39.5, 18.2,
Scheme 3. Proposed mechanism of the ring expansion.
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13.9, 12.4 ppm; IR (KBr): n˜ =3342, 1728, 1434, 1350, 734 cmÀ1
;
1518, 1342, 854, 748 cmÀ1; HRMS (ESI) m/z calcd for C23H22N3O4
404.1610 [M+H]+; found: 404.1608.
HRMS (ESI) m/z calcd for C19H23N2O2: 311.1760 [M+H]+; found:
311.1757.
Methyl 2-(9-benzyl-2-(pent-2-ynyl)-2,3,4,9-tetrahydro-1H-pyrido-
[3,4-b]indol-1-yl)acetate (1h): White solids. M.p. 113–1168C; Rf
(PE/EtOAc, 3:1)=0.76; H NMR (300 MHz, CDCl3): d=7.61–7.51 (m,
Methyl 2-(2-(4-(tert-butyldiphenylsilyloxy)but-2-ynyl)-2,3,4,9-tet-
rahydro-1H-pyrido[3,4-b]indol-1-yl) acetate (1c): Oil. Rf (PE/EtOAc,
5:1)=0.68; H NMR (300 MHz, CDCl3) d=8.65 (brs, 1H), 7.78 (d, J=
1
1
1H), 7.35–7.06 (m, 6H), 7.02–6.99 (m, 2H), 5.39–5.26 (m, 2H), 4.58
(dd, J1 =9.9, J2 =2.9 Hz, 1H), 3.70 (s, 3H), 3.49–3.33 (m, 2H), 3.33–
3.22 (m, 2H), 3.08–2.87 (m, 1H), 2.80 (dd, J1 =15.8 Hz, J2 =9.9 Hz,
1H), 2.67–2.59 (m, 1H), 2.50 (dd, J1 =15.8 Hz, J2 =3.1 Hz, 1H), 2.16
(qt, J1 =7.5, J2 =2.1 Hz, 2H), 1.09 ppm (t, J=7.5 Hz, 3H); 13C NMR
(75 MHz, CDCl3): d=171.6, 137.5, 137.0, 134.2, 128.7, 127.3, 127.0,
126.0, 121.7, 119.3, 118.2, 109.6, 107.8, 85.9, 75.6, 52.1, 51.7, 46.6,
42.64, 42.57, 39.8, 17.1, 13.8, 12.4 ppm; IR (KBr): n˜ =2915, 1739,
1467, 1431, 1285, 1172, 1030, 744 cmÀ1; HRMS (ESI) m/z calcd for
C26H29N2O2 401.2229 [M+H]+; found: 401.2226.
6.4 Hz, 4H), 7.56 (d, J=7.5 Hz, 1H), 7.52–7.33 (m, 7H), 7.25–7.10
(m, 2H), 4.53–4.31 (m, 3H), 3.78 (s, 3H), 3.64–3.51 (m, 2H), 3.24–
3.02 (m, 3H), 2.93–2.66 (m, 3H), 1.14 ppm (s, 9H); 13C NMR
(75 MHz, CDCl3) d=173.8, 135.7, 135.5, 133.6, 133.0, 129.7, 127.6,
126.7, 121.6, 119.1, 118.1, 110.9, 107.4, 83.1, 81.0, 52.7, 52.6, 51.9,
45.5, 42.9, 39.5, 26.6, 19.1, 18.2 ppm; IR (KBr): n˜ =3413, 2929, 1726,
1429, 1111, 741, 704 cmÀ1; HRMS (ESI) m/z calcd for C34H39N2O3Si:
551.2730 [M+H]+; found: 551.2729.
Methyl 2-(2-(undec-5-yn-4-yl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-
b]indol-1-yl)acetate (1d): Mixed diastereomers were obtained.
1H NMR (300 MHz, CDCl3): d=8.66 (brs, 1H), 8.46 (brs, 1H), 7.51 (t,
J=6.3 Hz, 2H), 7.33 (t, J=7.0 Hz, 2H), 7.19–7.06 (m, 4H), 4.62 (dd,
J1 =9.6, J2 =4.1 Hz, 1H), 4.48 (dd, J1 =9.9, J2 =4.1 Hz, 1H), 3.78 (s,
3H), 3.76 (s, 3H), 3.64 (t, J=6.9 Hz, 1H), 3.49 (t, J=7.1 Hz, 1H),
3.19–2.61 (m, 12H), 2.18–2.15 (m, 2H), 2.04–1.99 (m, 2H), 1.77–1.23
(m, 19H), 1.01–0.87 ppm (m, 13H); 13C NMR (75 MHz, CDCl3): d=
174.3, 135.7, 135.4, 135.3, 135.0, 126.9, 121.3, 121.27, 119.0, 118.0,
117.99, 117.94, 110.8, 110.7, 108.7, 108.5, 85.4, 84.9, 80.2, 78.5, 54.1,
52.9, 52.0, 51.9, 51.7, 43.2, 39.5, 37.3, 36.6, 31.0, 30.9, 28.5, 22.1,
22.0, 20.4, 20.0, 19.7, 19.5, 18.6, 18.5, 13.9, 13.8 ppm; IR (KBr): n˜ =
3404, 2956, 2931, 1725, 1464, 1437, 1349, 741 cmÀ1;HRMS (ESI) m/z
calcd for C25H35N2O2 395.2699 [M+H]+; found: 395.2697.
Methyl 2-(9-methyl-2-(pent-2-ynyl)-2,3,4,9-tetrahydro-1H-pyrido-
[3,4-b]indol-1-yl)acetate (1i): White solids. M.p. 89–918C; Rf (PE/
EtOAc, 3:1)=0.69; H NMR (300 MHz, CDCl3) d=7.49 (d, J=7.7 Hz,
1
1H), 7.29 (d, J=8.1 Hz, 1H), 7.21 (t, J=7.5 Hz, 1H), 7.10 (t, J=
7.3 Hz, 1H), 4.59 (dd, J1 =9.8, J2 =2.6 Hz, 1H), 3.77 (s, 3H), 3.66 (s,
3H), 3.52–3.34 (m, 2H), 3.40–3.07 (m, 2H), 2.95–2.79 (m, 2H), 2.72–
2.48 (m, 2H), 2.20 (q, J=7.4 Hz, 2H), 1.12 ppm (t, J=7.5 Hz, 3H);
13C NMR (75 MHz, CDCl3): d=171.7, 137.2, 134.2, 126.6, 121.4,
119.0, 118.2, 108.8, 107.1, 85.9, 75.7, 52.2, 51.8, 42.8, 39.6, 29.6, 17.0,
13.9, 12.5 ppm; IR (KBr): n˜ =2945, 2797, 1738, 1472, 1438, 1364,
1330, 1167, 737 cmÀ1
; HRMS (ESI) m/z calcd for C20H25N2O2
325.1916 [M+H]+; found: 325.1915.
Methyl 2-(6-chloro-2-(pent-2-ynyl)-2,3,4,9-tetrahydro-1H-pyrido-
[3,4-b]indol-1-yl)acetate (1j): Yellow solids. M.p. 122–1248C; Rf
Methyl 2-(2-(3-phenylprop-2-ynyl)-2,3,4,9-tetrahydro-1H-pyrido-
1
(PE/EtOAc 3:1)=0.50; H NMR (300 MHz, CDCl3): d=8.69 (brs, 1H),
1
[3,4-b]indol-1-yl)acetate (1e): Oil. Rf (PE/EtOAc 3:1)=0.55; H NMR
7.44 (s, 1H), 7.22 (d, J=8.6 Hz, 1H), 7.09 (d, J=8.6 Hz, 1H), 4.38
(dd, J1 =9.9, J2 =2.0 Hz, 1H), 3.76 (s, 3H), 3.57–3.41 (m, 2H), 3.29–
2.92 (m, 3H), 2.92–2.71 (m, 2H), 2.61 (dt, J1 =15.7, J2 =4.5 Hz, 1H),
2.20 (q, J=7.4 Hz, 2H), 1.12 ppm (t, J=7.5 Hz, 3H); 13C NMR
(75 MHz, CDCl3): d=174.1, 135.5, 134.0, 127.8, 124.8, 121.7, 117.6,
111.8, 107.4, 86.7, 74.7, 52.2, 52.0, 45.6, 43.0, 39.2, 18.3, 13.9,
12.4 ppm; IR (KBr): n˜ =3338, 2951, 2231, 1725, 1439, 1349, 1317,
1270, 1163, 801 cmÀ1; HRMS (ESI) m/z calcd for C19H22ClN2O2:
345.1370 [M+H]+; found 345.1371.
(300 MHz, CDCl3): d=8.61 (brs, 1H), 7.54 (d, J=7.6 Hz, 1H), 7.49–
7.40 (m, 2H), 7.40–7.28 (m, 4H), 7.20 (t, J=7.3 Hz, 1H), 7.13 (t, J=
7.3 Hz, 1H), 4.53 (dd, J1 =9.4, J2 =3.4 Hz, 1H), 3.85–3.73 (m, 5H),
3.39–3.15 (m, 2H), 3.10 (dd, J1 =17.0, J2 =3.7 Hz, 1H), 3.03–2.79 (m,
2H), 2.73 ppm (dt, J1 =15.7, J2 =4.1 Hz, 1H); 13C NMR (75 MHz,
CDCl3): d=173.8, 135.7, 133.6, 131.7, 128.2, 128.1, 126.7, 123.0,
121.7, 119.2, 118.1, 110.9, 107.6, 85.3, 84.9, 52.6, 52.0, 45.7, 43.5,
39.6, 18.3 ppm; IR (KBr): n˜ =3399, 2949, 1728, 1489, 1441, 757,
745 cmÀ1; HRMS (ESI) m/z calcd for C23H23N2O2: 359.1760 [M+H]+;
found: 359.1759.
Methyl 2-(6-methyl-2-(pent-2-ynyl)-2,3,4,9-tetrahydro-1H-pyrido-
[3,4-b]indol-1-yl)acetate (1k): White solids. M.p. 123–1258C; Rf
1
Methyl
2-(2-(3-(4-methoxyphenyl)prop-2-ynyl)-2,3,4,9-tetrahy-
(PE/EtOAc 3:1)=0.56; H NMR (300 MHz, CDCl3): d=8.44 (brs, 1H),
dro-1H-pyrido[3,4-b]indol-1-yl)acetate (1 f): Oil. Rf (PE/EtOAc
7.27 (s, 1H), 7.21 (d, J=8.2 Hz, 1H), 6.98 (d, J=8.1 Hz, 1H), 4.38
(dd, J1 =9.7, J2 =2.6 Hz, 1H), 3.75 (s, 3H), 3.58–3.40 (m, 2H), 3.25–
2.92 (m, 3H), 2.92–2.76 (m, 2H), 2.76–2.50 (m, 1H), 2.44 (s, 3H),
2.21 (q, J=7.3 Hz, 2H), 1.13 ppm (t, J=7.5 Hz, 3H); 13C NMR
(75 MHz, CDCl3): d=174.0, 134.0, 128.4, 126.9, 123.1, 117.8, 110.5,
107.0, 86.5, 75.0, 52.4, 51.9, 45.6, 43.0, 39.6, 21.4, 18.2, 13.9,
12.4 ppm; IR (KBr): n˜ =3324, 2981, 2231, 1721, 1487, 1325, 1218,
818 cmÀ1; HRMS (ESI) m/z calculated for C20H25N2O2 [M+H]+
325.1916, found 325.1917.
1
2:1)=0.77; H NMR (300 MHz, CDCl3): d=8.62 (brs, 1H), 7.52 (d, J=
7.6 Hz, 1H), 7.41–7.31 (m, 3H), 7.19 (t, J=6.9 Hz, 1H), 7.12 (t, J=
7.4 Hz, 1H), 6.82 (d, J=8.8 Hz, 2H), 4.51 (dd, J1 =9.6, J2 =3.5 Hz,
1H), 3.80–3.76 (m, 8H), 3.35–3.14 (m, 2H), 3.08 (dd, J1 =17.0, J2 =
3.9 Hz, 1H), 3.01–2.78 (m, 2H), 2.71 ppm (dt, J1 =15.7, J2 =4.3 Hz,
1H); 13C NMR (75 MHz, CDCl3): d=173.9, 159.4, 135.7, 133.6, 133.1,
126.7, 121.7, 119.2, 118.1, 115.1, 113.8, 110.9, 107.5, 84.7, 83.7, 55.2,
52.6, 52.0, 45.7, 43.5, 39.6, 18.3 ppm; IR (KBr): n˜ =3399, 2950, 1727,
1606, 1509, 1247, 1172, 1030, 834, 745 cmÀ1; HRMS (ESI) m/z calcd
for C24H25N2O3: 389.1865 [M+H]+; found: 389.1866.
Methyl
2-(6-methoxy-2-(pent-2-ynyl)-2,3,4,9-tetrahydro-1H-
pyrido[3,4-b]indol-1-yl)acetate (1l): White solid. M.p. 145–1478C;
Rf (PE/EtOAc, 3:1)=0.58; 1H NMR (300 MHz, CDCl3): d=8.45 (brs,
1H), 7.21 (d, J=8.7 Hz, 1H), 6.94 (s, 1H), 6.81 (d, J=8.6 Hz, 1H),
4.51–4.28 (m, 1H), 3.85 (s, 3H), 3.75 (s, 3H), 3.43–3.55 (m, 2H),
3.41–2.95 (m, 3H), 2.95–2.69 (m, 2H), 2.61 (dt, J1 =8.5, J2 =3.9 Hz,
1H), 2.21 (q, J=7.2 Hz, 2H), 1.13 ppm (t, J=7.5 Hz, 3H); 13C NMR
(75 MHz, CDCl3): d=174.0, 153.8, 134.7, 130.8, 127.1, 111.5, 111.4,
107.3, 100.3, 86.6, 74.9, 55.9, 52.4, 51.9, 45.5, 43.0, 39.5, 18.3, 13.9,
12.4 ppm; IR (KBr): n˜ =3363, 2944, 2233, 1728, 1440, 1350, 1319,
1166, 799 cmÀ1; HRMS (ESI) m/z calculated for C20H25N2O3 341.1865
[M+H]+; found: 341.1865.
Methyl 2-(2-(3-(4-nitrophenyl)prop-2-ynyl)-2,3,4,9-tetrahydro-1H-
pyrido[3,4-b]indol-1-yl)acetate (1g): Oil. Rf (PE/EtOAc 2:1)=0.75;
1H NMR (300 MHz, CDCl3): d=8.57 (brs, 1H), 8.11 (d, J=8.7 Hz,
2H), 7.51 (d, J=8.1 Hz, 1H), 7.47 (d, J=8.7 Hz, 2H), 7.34 (d, J=
7.9 Hz, 1H), 7.19 (t, J=7.3 Hz, 1H), 7.11 (t, J=7.3 Hz, 1H), 4.49 (dd,
J1 =9.0, J2 =4.0 Hz, 1H), 3.80–3.74 (m, 5H), 3.34–3.15 (m, 2H), 3.15–
2.80 (m, 3H), 2.71 ppm (dt, J1 =15.9, J2 =3.6 Hz, 1H); 13C NMR
(75 MHz, CDCl3): d=173.7, 146.9, 135.7, 133.2, 132.3, 129.8, 126.6,
123.4, 121.9, 119.3, 118.1, 111.0, 107.6, 91.4, 83.1, 52.8, 52.1, 45.6,
43.6, 39.8, 18.1 ppm; IR (KBr): n˜ =3404, 2950, 2232, 1727, 1593,
Chem. Eur. J. 2014, 20, 2925 – 2932
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(S)-Methyl 1-(2-methoxy-2-oxoethyl)-2-(pent-2-ynyl)-2,3,4,9-tet-
rahydro-1H-pyrido[3,4-b]indole-3-carboxylate (1m): Mixed diaste-
reomers were obtained. 1H NMR (300 MHz, CDCl3): d=8.84 (s,
0.5H), 8.65 (s, 1H), 7.49 (d, J=7.7 Hz, 1.5H), 7.32 (d, J=7.9 Hz,
1.5H), 7.19–7.08 (m, 3H), 4.73 (dd, J=10.6, 2.8 Hz, 1H), 4.64–4.41
(m, 0.5H), 4.17–3.96 (m, 1.5H), 3.76 (dd, J1 =6.1, J2 =4.8 Hz, 9H),
3.72–3.33 (m, 3H), 3.21–2.91 (m, 4.5H), 2.91–2.57 (m, 1.5H), 2.30–
2.10 (m, 3H), 1.14–1.08 ppm (m, 4.5 Hz); 13C NMR (75 MHz, CDCl3):
d=174.5, 173.8, 173.7, 172.5, 135.8, 133.6, 133.5, 126.4, 126.2,
121.7, 121.6, 119.2, 118.0, 110.9, 106.0, 105.7, 87.7, 86.4, 75.2, 73.6,
59.1, 57.1, 52.4, 52.0, 51.96, 42.4, 40.2, 39.6, 39.2, 23.3, 21.0, 13.8,
13.7, 12.4, 12.3 ppm; IR (KBr): n˜ =3402, 2951, 2235, 1732, 1437,
744 cmÀ1; HRMS (ESI) m/z calcd for C21H25N2O4: 369.1814 [M+H]+;
found: 369.1808.
(E)-Methyl 3-(6-((tert-butyldiphenylsilyloxy)methyl)-1H-azocino-
[5,4-b]indol-3(2H,4H,7H)-yl)propanoate (2c): Oil. Rf (PE/EtOAc
5:1)=0.62; H NMR (300 MHz, CDCl3): d=9.16 (brs, 1H), 7.74 (dd,
1
J1 =7.7, J2 =1.4 Hz, 4H), 7.55 (d, J=7.7 Hz, 1H), 7.51–7.37 (m, 6H),
7.30 (d, J=7.9 Hz, 1H), 7.22 (td, J1 =7.7, J2 =1.3 Hz, 1H), 7.13 (td,
J1 =7.8, J2 =1.3 Hz, 1H), 5.70 (t, J=7.9 Hz, 1H), 4.52 (s, 2H), 3.69 (s,
3H), 3.37 (d, J=7.1 Hz, 2H), 3.09–2.96 (m, 4H), 2.88 (t, J=7.3 Hz,
2H), 2.56 (t, J=7.3 Hz, 2H), 1.16 ppm (s, 9H); 13C NMR (75 MHz,
CDCl3): d=172.9, 135.6, 135.5, 134.9, 132.7, 131.6, 130.0, 127.8,
125.9, 122.4, 119.2, 118.5, 113.8, 110.6, 69.1, 51.6, 50.8, 50.2, 49.6,
33.2, 26.9, 22.8, 19.2 ppm; IR (KBr): n˜ =3422, 2930, 2856, 1739,
1428, 1112, 741, 702 cmÀ1; HRMS (ESI): m/z calcd for C34H41N2O3Si:
553.2886 [M+H]+; found: 553.2885.
(E)-Methyl
3-((Z)-6-pentyl-4-propyl-1H-azocino[5,4-b]indol-
2-(2-(pent-2-ynyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)-
1-phenylethanone (1n): Yellow solids. M.p. 123–1258C; Rf (PE/
EtOAc, 3:1)=0.51; 1H NMR (300 MHz, CDCl3): d=8.68 (brs, 1H),
8.01 (d, J=7.4 Hz, 2H), 7.60 (t, J=7.3 Hz, 1H), 7.55–7.44 (m, 3H),
7.33 (d, J=7.8 Hz, 1H), 7.16 (t, J=7.4 Hz, 1H), 7.10 (t, J=7.4 Hz,
1H), 4.67 (dd, J1 =8.9 Hz, J2 =3.3 Hz, 1H), 3.82 (dd, J1 =18.4, J2 =
2.3 Hz, 1H), 3.71–3.44 (m, 3H), 3.44–3.06 (m, 2H), 3.06–2.82 (m,
1H), 2.69 (dt, J1 =15.8, J2 =4.0 Hz, 1H), 2.22 (q, J=7.4 Hz, 2H),
1.14 ppm (t, J=7.5 Hz, 3H); 13C NMR (75 MHz, CDCl3): d=200.8,
136.5, 135.5, 134.4, 133.6, 128.6, 128.0, 126.7, 121.5, 119.0, 117.9,
110.9, 107.0, 86.5, 75.2, 52.0, 45.5, 43.1, 18.0, 13.9, 12.4 ppm; IR
(KBr) n˜ =2937, 2848, 2228, 1684, 1444, 1362, 738 cmÀ1; HRMS (ESI)
m/z calcd for C24H25N2O: 357.1967 [M+H]+; found: 357.1964.
3(2H,4H,7H)-yl)acrylate (2d): White solid. M.p. 136–1398C; Rf (PE/
EtOAc, 3:1)=0.64; 1H NMR (300 MHz, CDCl3): d=8.24 (brs, 1H),
7.59 (d, J=7.7 Hz, 2H), 7.37 (d, J=7.9 Hz, 1H), 7.25–7.09 (m, 2H),
5.69 (d, J=8.0 Hz, 1H), 4.78 (d, J=13.1 Hz, 1H), 3.86–3.72 (m, 1H),
3.69 (s, 3H), 3.22 (dd, J1 =14.9, J2 =5.2 Hz, 2H), 2.84–2.21 (m, 4H),
1.91–1.50 (m, 2H), 1.39–1.18 (m, 8H), 0.87–0.78 ppm (m, 6H);
13C NMR (75 MHz, CDCl3): d=170.4, 147.7, 135.9, 134.5, 133.9,
130.9, 128.0, 122.5, 119.5, 118.2, 114.5, 110.8, 85.4, 60.3, 50.6, 36.8,
˜
36.1, 31.3, 29.7, 28.1, 23.2, 22.4, 19.3, 14.0, 13.8 ppm; IR (KBr): n=
3303, 2929, 1673, 1596, 1159, 792, 737 cmÀ1; HRMS (ESI) m/z calcd
for C25H35N2O2: 395.2699 [M+H]+; found: 395.2697.
(E)-Methyl
3-((Z)-6-phenyl-1H-azocino[5,4-b]indol-3(2H,4H,7H)-
yl)acrylate (2e): White solid. M.p. 259–2618C; Rf (PE/EtOAc, 3:1)=
1
0.50; H NMR (300 MHz, [D6]DMSO): d=10.81 (brs, 1H), 7.60 (d, J=
7.7 Hz, 1H), 7.43–7.18 (m, 7H), 7.10 (t, J=7.3 Hz, 1H), 7.03 (t, J=
7.3 Hz, 1H), 6.44 (t, J=6.4 Hz, 1H), 4.81 (d, J=12.4 Hz, 1H), 3.84–
3.68 (m, 2H), 3.48 (s, 3H), 3.45–3.36 (m, 2H), 3.06–2.77 ppm (m,
2H); 13C NMR (75 MHz, [D6]DMSO): d=168.8, 151.9, 140.2, 136.5,
136.0, 132.7, 128.4, 128.0, 127.6, 126.8, 124.2, 121.8, 118.6, 118.2,
113.5, 111.3, 82.7, 79.2, 53.9, 49.7, 46.9, 25.6 ppm; IR (KBr): n˜ =3289,
1674, 1599, 1422, 1148, 771 cmÀ1; HRMS (ESI) m/z calcd for
C23H23N2O2: 359.1760 [M+H]+; found: 359.1756.
General procedure for the preparation of 1H-azocino[5,4-
b]indole from 2-propargyl-b-tetrahydrocarboline through
a gold(I)-catalyzed ring expansion
Triphenylphosphine gold(I) bis(trifluoromethanesulfonyl)imidate
(3.0 mg, 0.004 mmol) was added in one portion to a stirred solu-
tion of 2-propargyl-b-tetrahydrocarboline ( 0.4 mmol) in toluene
(4.0 mL). The reaction was heated at 1108C for 2 h. After cooling,
the solution was concentrated under vacuum pressure and the res-
idue was purified by column chromatography with EtOAc/PE (1:2)
as eluent to give pure 1H-azocino[5,4-b]indole.
(E)-Methyl
3-((Z)-6-(4-methoxyphenyl)-1H-azocino[5,4-b]indol-
3(2H,4H,7H)-yl)acrylate (2 f): White solid. M.p. 221–2248C; Rf (PE/
EtOAc, 2:1)=0.73; 1H NMR (300 MHz, CDCl3) d=7.99 (brs, 1H),
7.62 (d, J=7.5 Hz, 1H), 7.41 (d, J=12.1 Hz, 1H), 7.33–7.12 (m, 6H),
6.85 (d, J=8.8 Hz, 2H), 6.29 (s, 1H), 4.80 (d, J=12.5 Hz, 1H), 3.81
(s, 3H), 3.77 (d, J=6.3 Hz, 2H), 3.62 (s, 3H), 3.45–3.32 (m, 2H),
3.10–2.97 ppm (m, 2H); 13C NMR (75 MHz, CDCl3): d=170.1, 159.9,
151.9, 136.6, 136.1, 132.1, 129.3, 127.3, 122.8, 122.1, 119.6, 118.3,
113.9, 110.9, 83.6, 55.3, 54.2, 50.5, 47.2, 26.1 ppm; IR (KBr): n˜ =3290,
2912, 1671, 1595, 1509, 1360, 1250, 1157, 837 cmÀ1; HRMS (ESI): m/
z calcd for C24H25N2O3: 389.1865 [M+H]+; found: 389.1863.
(Z)-Methyl 3-(1H-azocino[5,4-b]indol-3(2H,4H,7H)-yl)propanoate
(2a): Oil. Rf (CH2Cl2/MeOH 20:1)=0.24; 1H NMR (300 MHz, CDCl3):
d=7.94 (brs, 1H), 7.49 (d, J=7.7 Hz, 1H), 7.27 (d, J=7.7 Hz, 1H),
7.18 (td, J1 =6.9, J2 =1.2 Hz, 1H), 7.11 (td, J1 =6.9, J2 =1.2 Hz, 1H),
6.66 (d, J=11.0 Hz, 1H), 5.86 (dt, J1 =10.9, J2 =7.8 Hz, 1H), 3.67 (s,
3H), 3.48 (d, J=7.8 Hz, 2H), 3.06–3.14 (m, 4H), 2.93 (t, J=7.3 Hz,
2H), 2.59 ppm (t, J=7.3 Hz, 2H); 13C NMR (75 MHz, CDCl3): d=
173.0, 135.9, 130.5, 128.8, 126.6, 125.4, 122.6, 119.5, 118.6, 113.8,
110.5, 51.7, 51.0, 50.0, 49.8, 33.2, 22.6 ppm; IR (KBr) n˜ =3375, 2948,
1741, 1591, 1461, 1336, 1178, 769, 742 cmÀ1; HRMS (ESI) m/z calcd
for C17H21N2O2: 285.1603 [M+H]+; found: 285.1602.
(E)-Methyl
3-((Z)-6-(4-nitrophenyl)-1H-azocino[5,4-b]indol-
3(2H,4H,7H)-yl)acrylate (2g): White solid. M.p. 261–2638C; Rf (PE/
1
EtOAc 2:1)=0.71; H NMR (300 MHz, CDCl3): d=8.15 (d, J=8.7 Hz,
2H), 7.98 (brs, 1H), 7.63 (d, J=7.6 Hz, 1H), 7.40 (d, J=8.7 Hz, 2H),
7.35–7.15 (m, 4H), 6.43 (t, J=6.6 Hz, 1H), 4.75 (d, J=13.0 Hz, 1H),
3.87 (d, J=6.1 Hz, 2H), 3.60 (s, 3H), 3.48–3.35 (m, 2H), 3.14–2.98
ppm (m, 2H); 13C NMR (75 MHz, CDCl3): d=169.9, 151.7, 147.4,
146.3, 136.5, 135.2, 131.2, 128.8, 127.0, 126.8, 123.6, 123.4, 120.0,
118.4, 115.5, 111.2, 84.0, 54.5, 50.5, 47.3, 29.6, 25.7 ppm; IR (KBr):
(E)-Methyl 3-((Z)-6-ethyl-1H-azocino[5,4-b]indol-3(2H,4H,7H)-yl)-
acrylate (2b): White solids. M.p. 100–1028C; Rf (PE/EtOAc 2:1)=
0.59; 1H NMR (400 MHz, CDCl3): d=8.59 (brs, 1H), 7.55 (d, J=
7.8 Hz, 1H), 7.42 (d, J=12.1 Hz, 1H), 7.36 (d, J=7.8 Hz, 1H), 7.22 (t,
J=7.2 Hz, 1H), 7.16 (t, J=7.4 Hz, 1H), 5.92 (s, 1H), 4.77 (d, J=
12.9 Hz, 1H), 3.69 (s, 3H), 3.65–3.54 (m, 2H), 3.41–3.24 (m, 2H),
3.00–2.83 (m, 2H), 2.48 (q, J=7.4 Hz, 2H), 0.99 ppm (t, J=7.4 Hz,
3H); 13C NMR (100 MHz, CDCl3): d=170.4, 152.0, 138.0, 136.1,
133.9, 127.5, 122.3, 121.0, 119.4, 118.0, 112.7, 110.9, 83.0, 54.4, 50.5,
46.7, 29.6, 25.9, 13.0 ppm; IR (KBr): n˜ =3289, 2930, 1671, 1597,
1421, 1355, 1155, 746 cmÀ1; HRMS (ESI): m/z calcd for C19H23N2O2:
311.1760 [M+H]+; found: 311.1757.
n˜ =3267, 2948, 1673, 1592, 1517, 1443, 1342, 1164, 853 cmÀ1
;
HRMS (ESI) m/z calcd for C23H22N3O4: 404.1610 [M+H]+; found:
404.1609.
(E)-Methyl
3-((Z)-7-benzyl-6-ethyl-1H-azocino[5,4-b]indol-
3(2H,4H,7H)-yl)acrylate (2h): White solid. M.p. 94–968C; Rf (PE/
1
EtOAc 3:1)=0.70; H NMR (300 MHz, CDCl3): d=7.75–7.55 (m, 1H),
7.52 (d, J=13.0 Hz, 1H), 7.35–7.23 (m, 3H), 7.23–7.13 (m, 3H),
Chem. Eur. J. 2014, 20, 2925 – 2932
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7.08–6.95 (m, 2H), 6.19 (s, 1H), 5.37–5.21 (m, 2H), 4.83 (d, J=
13.0 Hz, 1H), 3.87–3.75 (m, 1H), 3.71 (s, 3H), 3.67–3.48 (m, 1H),
3.34 (dd, J1 =14.8, J2 =5.4 Hz, 1H), 3.19–3.01 (m, 2H), 2.53–2.42 (m,
1H), 2.36 (q, J=7.6 Hz, 2H), 0.90 ppm (t, J=7.4 Hz, 3H); 13C NMR
(75 MHz, CDCl3): d=170.2, 152.1, 138.2, 137.8, 137.6, 136.5, 128.5,
127.2, 125.8, 124.6, 122.4, 119.6, 118.2, 114.2, 110.1, 83.2, 54.5, 50.4,
48.3, 46.0, 29.5, 26.3, 13.0 ppm; IR (KBr): n˜ =2929, 1689, 1605, 1352,
1145, 744 cmÀ1; HRMS (ESI): m/z calcd for C26H29N2O2: 401.2229
[M+H]+; found: 401.2224.
3H); 13C NMR (75 MHz, CDCl3): d=170.7, 170.1, 152.3, 136.1, 122.4,
119.6, 118.5, 110.9, 109.4, 84.8, 52.1, 50.6, 29.6, 13.0 ppm; IR (KBr):
n˜ =3249, 1741, 1654, 1623, 1429, 1249, 1147, 727 cmÀ1; HRMS (ESI)
m/z calcd for C21H25N2O4: 369.1814 [M+H]+; found: 369.1810.
(Z)-3-(6-Ethyl-1H-azocino[5,4-b]indol-3(2H,4H,7H)-yl)-1-phenyl-
propan-1-ol (2n): Oil. Rf (CH2Cl2/MeOH 20:1)=0.48; 1H NMR
(300 MHz, CDCl3): d=8.15 (brs, 1H), 7.54 (d, J=7.6 Hz, 1H), 7.45–
7.29 (m, 5H), 7.28–7.09 (m, 3H), 5.80 (s, 1H), 5.00 (dd, J1 =7.1 Hz,
J2 =3.7 Hz, 1H), 4.54–3.56 (m, 2H), 3.62–2.64 (m, 7H), 2.48 (q, J=
7.4 Hz, 2H), 2.18–1.72 (m, 2H), 1.06 ppm (t, J=7.4 Hz, 3H);
13C NMR (75 MHz, CDCl3): d=145.0, 138.5, 136.0, 128.2, 126.8,
125.5, 122.3, 119.4, 118.3, 114.1, 110.7, 75.4, 54.7, 51.1, 34.1, 29.7,
29.5, 22.7, 13.5 ppm; IR (KBr): n˜ =3207, 2922, 2807, 1465, 1448,
(E)-Methyl
3-((Z)-6-ethyl-7-methyl-1H-azocino[5,4-b]indol-
3(2H,4H,7H)-yl)acrylate (2i): White solid. M.p. 123–1258C; Rf (PE/
1
EtOAc, 3:1)=0.63; H NMR (300 MHz, CDCl3): d=7.55 (d, J=7.8 Hz,
1H), 7.48 (d, J=12.6 Hz, 1H), 7.33 (d, J=8.0 Hz, 1H), 7.27 (t, J=
7.3 Hz, 1H), 7.16 (t, J=7.3 Hz, 1H), 6.24 (s, 1H), 4.82 (d, J=12.7 Hz,
1H), 3.85 (dd, J1 =14.2, J2 =5.8 Hz, 1H), 3.70 (s, 3H), 3.67 (s, 3H),
3.51–3.60 (m, 1H), 3.15–3.32 (m, 2H), 3.11–2.85 (m, 1H), 2.65–2.31
(m, 3H), 0.93 ppm (t, J=7.4 Hz, 3H); 13C NMR (75 MHz, CDCl3): d=
170.2, 152.1, 138.1, 137.8, 126.8, 124.3, 122.1, 119.2, 118.1, 113.3,
109.1, 83.1, 54.5, 50.5, 46.2, 31.3, 29.4, 26.3, 13.0 ppm; IR (KBr): n˜ =
2931, 1692, 1606, 1467, 1354, 1145, 743 cmÀ1; HRMS (ESI) m/z calcd
for C20H25N2O2: 325.1916 [M+H]+; found: 325.1914.
1055, 1026, 727 cmÀ1
361.2280 [M+H]+; found: 361.2277.
Methyl 3-(5-methylene-1,2,4,5-tetrahydroazepino[4,5-b]indol-
; HRMS (ESI) m/z calcd for C24H29N2O:
1
3(6H)-yl)propanoate (3): Oil. Rf (CH2Cl2/MeOH 20:1)=0.33; H NMR
(400 MHz, CDCl3): d=7.97 (brs, 1H), 7.50 (d, J=7.9 Hz, 1H), 7.29 (d,
J=8.1 Hz, 1H), 7.19 (td, J1 =7.8, J2 =1.2 Hz, 1H), 7.10 (td, J1 =7.8,
J2 =1.2 Hz, 1H), 5.30 (s, 1H), 5.13 (s, 1H), 3.77 (s, 2H), 3.71 (s, 3H),
3.32–3.23 (m, 2H), 2.96–3.02 (m, 4H), 2.59 ppm (t, J=7.2 Hz, 2H);
13C NMR (100 MHz, CDCl3): d=173.1, 139.6, 135.8, 134.2, 128.9,
122.9, 119.4, 118.7, 114.6, 111.9, 110.5, 59.9, 54.1, 51.6, 46.5, 32.9,
22.7 ppm; IR (KBr): n˜ =3390, 2922, 2843, 1732, 1436, 1333, 1195,
740 cmÀ1; HRMS (ESI): m/z calcd for C17H21N2O2: 285.1603 [M+H]+;
found: 285.1601.
(E)-Methyl
3-((Z)-10-chloro-6-ethyl-1H-azocino[5,4-b]indol-
3(2H,4H,7H)-yl)acrylate (2j): White solid. M.p. 177–1798C. Rf (PE/
1
EtOAc, 3:1)=0.46; H NMR (300 MHz, CDCl3): d=8.32 (s, 1H), 7.48
(s, 1H), 7.30 (d, J=12.8 Hz, 1H), 7.24 (d, J=8.1 Hz, 1H), 7.14 (d, J=
8.6 Hz, 1H), 5.88 (t, J=5.2 Hz, 1H), 4.69 (d, J=12.8 Hz, 1H), 3.69–
3.51 (m, 5H), 3.38–3.22 (m, 2H), 2.92–2.78 (m, 2H), 2.44 (q, J=
7.4 Hz, 2H), 0.98 ppm (t, J=7.4 Hz, 3H); 13C NMR (75 MHz, CDCl3):
d=170.3, 151.9, 137.2, 135.5, 134.5, 132.2, 128.6, 125.2, 122.6,
121.5, 117.5, 111.9, 83.2, 54.6, 50.5, 46.9, 29.7, 25.7, 13.0 ppm; IR
Acknowledgements
(KBr) n˜ =3283, 2966, 1671, 1600, 1443, 1359, 1156, 1050, 795 cmÀ1
;
We appreciated the fund supported by National Science Foun-
dation of China (20802034, 21032002).
HRMS (ESI) m/z calcd for C19H22ClN2O2: 345.1370 [M+H]+; found:
345.1369.
(E)-Methyl
3-((Z)-6-ethyl-10-methyl-1H-azocino[5,4-b]indol-
Keywords: gold
expansion · X-ray diffraction
· indoles · reaction mechanisms · ring
3(2H,4H,7H)-yl)acrylate (2k): White solid. M.p. 183–1858C. Rf (PE/
EtOAc, 3:1)=0.50; 1H NMR (300 MHz, CDCl3) d=8.44 (brs, 1H),
7.42 (d, J=12.9 Hz, 1H), 7.33 (d, J=8.2 Hz, 1H), 7.24 (s, 1H), 7.05
(d, J=8.2 Hz, 1H), 5.91 (s, 1H), 4.76 (d, J=12.9 Hz, 1H), 3.69 (s,
3H), 3.62–3.52 (m, 2H), 3.38–3.22 (m, 2H), 2.96–2.79 (m, 2H), 2.55–
2.24 (m, 5H), 0.98 ppm (t, J=7.4 Hz, 3H); 13C NMR (75 MHz, CDCl3)
d=170.4, 152.0, 138.1, 134.4, 134.1, 128.7, 127.7, 123.9, 120.8,
117.7, 112.4, 110.6, 82.9, 54.4, 50.5, 46.7, 29.6, 25.8, 21.4, 13.0 ppm;
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;
325.1914.
(E)-Methyl
3-((Z)-6-ethyl-10-methoxy-1H-azocino[5,4-b]indol-
3(2H,4H,7H)-yl)acrylate (2l): White solid. M.p. 210–2128C; Rf (PE/
EtOAc, 3:1)=0.51; 1H NMR (300 MHz, CDCl3): d=8.05 (brs, 1H),
7.38 (d, J=13.0 Hz, 1H), 7.24 (d, J=8.7 Hz, 1H), 6.96 (s, 1H), 6.88
(d, J=8.7 Hz, 1H), 5.91 (s, 1H), 4.73 (d, J=13.0 Hz, 1H), 3.88 (s,
3H), 3.72–3.57 (m, 5H), 3.40–3.28 (m, 2H), 2.96–2.81 (m, 2H), 2.44
(q, J=7.3 Hz, 2H), 0.98 ppm (t, J=7.4 Hz, 3H); 13C NMR (75 MHz,
CDCl3): d=170.4, 154.0, 152.0, 137.9, 134.8, 131.3, 127.9, 120.8,
112.5, 111.7, 99.9, 83.0, 55.9, 54.5, 50.5, 46.7, 29.7, 25.9, 13.0 ppm;
IR (KBr): n˜ =3298, 2929, 1672, 1599, 1359, 1155, 788 cmÀ1; HRMS
(ESI): m/z calcd for C20H25N2O3: 341.1865 [M+H]+; found: 341.1863.
(S, Z)-Methyl 6-ethyl-3-((E)-3-methoxy-3-oxoprop-1-enyl)-2,3,4,7-
tetrahydro-1H-azocino[5,4-b]indole-2-carboxylate (2m): White
solids. M.p. 198–2008C; Rf (PE/EtOAc 3:1)=0.64; H NMR (300 MHz,
CDCl3): d=8.22 (s, 1H), 7.58 (d, J=7.6 Hz, 2H), 7.31 (d, J=7.8 Hz,
1H), 7.17–7.11 (m, 2H), 6.25–5.77 (m, 1H), 5.09–4.53 (m, 1H), 4.37–
4.03 (m, 1H), 3.90 (dd, J=15.6, 5.2 Hz, 2H), 3.78–3.35 (m, 7H),
2.89–2.55 (m, 1H), 2.44 (q, J=7.3 Hz, 2H), 0.97 ppm (t, J=7.4 Hz,
1
Chem. Eur. J. 2014, 20, 2925 – 2932
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Published online on February 12, 2014
Chem. Eur. J. 2014, 20, 2925 – 2932
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ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim