Palladium-catalyzed one-pot three- or four-component coupling of aryl iodides, alkynes, and amines through C-N bond cleavage: Efficient synthesis of indole derivatives

Article abstract of DOI:10.1002/chem.201304215

An efficient synthesis of N-substituted indole derivatives was realized by combining the Pd-catalyzed one-pot multicomponent coupling approach with cleavage of the C(sp³)-N bonds. Three or four components of aryl iodides, alkynes, and amines were involved in this coupling process. The cyclopentadiene-phosphine ligand showed high efficiency. A variety of aryl iodides, including cyclic and acyclic tertiary amino aryl iodides, and substituted 1-bromo-2-iodobenzene derivatives could be used. Both symmetric and unsymmetric alkynes substituted with alkyl, aryl, or trimethylsilyl groups could be applied. Cyclic secondary amines such as piperidine, morpholine, 4-methylpiperidine, 1-methylpiperazine, 2-methylpiperidine, and acyclic amines including secondary and primary amines all showed good reactivity. Further application of the resulting indole derivatives was demonstrated by the synthesis of benzosilolo[2,3-b]indole. All in one: Efficient synthesis of N-substituted indole derivatives was realized by combining a Pd-catalyzed one-pot multicomponent coupling approach with the cleavage of C(sp ³)-N bonds (see scheme). Three or four components of aryl iodides, alkynes, and amines were involved in this coupling process. The cyclopentadiene-phosphine ligand (1) showed high efficiency. Copyright

Full text of DOI:10.1002/chem.201304215

DOI: 10.1002/chem.201304215
Full Paper
&
Synthetic Methods
Palladium-Catalyzed One-Pot Three- or Four-Component Coupling
of Aryl Iodides, Alkynes, and Amines through CÀN Bond
Cleavage: Efficient Synthesis of Indole Derivatives
Wei Hao,[a] Weizhi Geng,[a] Wen-Xiong Zhang,[a] and Zhenfeng Xi*[a, b]
Dedicated to Professor Max Malacria on the occasion of his 65th birthday
Abstract: An efficient synthesis of N-substituted indole de-
rivatives was realized by combining the Pd-catalyzed one-
pot multicomponent coupling approach with cleavage of
the C(sp3)ÀN bonds. Three or four components of aryl io-
dides, alkynes, and amines were involved in this coupling
process. The cyclopentadiene–phosphine ligand showed
high efficiency. A variety of aryl iodides, including cyclic and
acyclic tertiary amino aryl iodides, and substituted 1-bromo-
2-iodobenzene derivatives could be used. Both symmetric
and unsymmetric alkynes substituted with alkyl, aryl, or tri-
methylsilyl groups could be applied. Cyclic secondary
amines such as piperidine, morpholine, 4-methylpiperidine,
1-methylpiperazine, 2-methylpiperidine, and acyclic amines
including secondary and primary amines all showed good
reactivity. Further application of the resulting indole deriva-
tives was demonstrated by the synthesis of benzosilolo[2,3-
b]indole.
Introduction
The synthesis of indole derivatives has been a major subject
both in academia and industry, since the substituted indole nu-
cleus appears in a vast number of natural products and phar-
macologically active compounds.[1–3] Among the many ap-
proaches to indole derivatives,[4] transition-metal-catalyzed
multicomponent coupling reactions have attracted much at-
tention.[5]
In addition, transition-metal-catalyzed cleavage of C(sp3)ÀN
bonds is of significant synthetic interest, because such bonds
are common in organic chemistry and usually unreactive.[6,7] In
this article, we report an efficient synthesis of N-substituted
indole derivatives by combining the palladium-catalyzed multi-
component coupling process with cleavage of the C(sp3)ÀN
bonds.
Scheme 1. Our previous work: palladium-catalyzed synthesis of pyrrole de-
rivatives through CÀN bond cleavage.
Scheme 1 outlines our previous report on the synthesis of
pyrrole derivatives from secondary amines and butadienyl di-
bromides. Formation of intermediates I and II was proposed.
These intermediates would undergo C(sp3)ÀN bond cleavage
and a second amination reaction, thus leading to the final pyr-
role derivatives. The cyclopentadiene–phosphine ligand L1
showed high efficiency.[8]
[a] W. Hao, W. Geng, Prof. Dr. W.-X. Zhang, Prof. Dr. Z. Xi
Beijing National Laboratory for Molecular Sciences (BNLMS)
Key Laboratory of Bioorganic Chemistry and
Molecular Engineering of Ministry of Education
College of Chemistry, Peking University
Beijing 100871 (China)
Enlightened by our previous findings (Scheme 1), we envi-
sioned that 1-(2-iodophenyl)piperidine would form intermedi-
ate III by means of Pd-catalyzed alkyne insertion into the CÀI
bond (Scheme 2). Intermediate III would undergo C(sp3)ÀN
bond cleavage and an amination reaction to lead to N-substi-
tuted indole derivatives. Similarly, 1-bromo-2-iodobenzene
would form intermediate IV by means of Pd-catalyzed selective
Fax: (+86)10-62751708
E-mail: zfxi@pku.edu.cn
[b] Prof. Dr. Z. Xi
State Key Laboratory of Organometallic Chemistry
Shanghai Institute of Organic Chemistry
CAS, Shanghai 200032 (China)
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201304215.
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Table 1. Substrate scope: different amines.
Scheme 2. This work: synthesis of N-substituted indole derivatives by com-
bining the palladium-catalyzed multicomponent coupling process with
cleavage of the C(sp3)ÀN bonds.
insertion of alkyne into the CÀI bond followed by amination.
Thus, synthesis of indole derivatives would be realized by
means of a Pd-catalyzed three- or four-component coupling
process.
Scheme 2 shows the new synthetic methods developed in
this work for the synthesis of N-substituted indole derivatives
by means of the palladium-catalyzed multicomponent cou-
pling of aryl iodides, alkynes, and amines. The cleavage of
C(sp3)ÀN bonds takes place as a key step in this catalytic pro-
cess. The cyclopentadiene–phosphine ligand L1 again shows
high efficiency.
Results and Discussion
Synthesis of N-substituted indole derivatives by means of
three-component coupling
We initially investigated the reaction of 1-(2-iodophenyl)piperi-
dine (1a) with 3-hexyne and piperidine to optimize the reac-
tion conditions. The optimal reaction conditions were realized
as follows: Pd(OAc)2 (2 mol%), L1 (5 mol%), LiOtBu (3 equiv),
110 8C, 12 h. With these optimized conditions, indole derivative
2a was obtained in 86% isolated yield (Table 1).
The substrate scope of this multicomponent cross-coupling
process for the synthesis of N-substituted indole derivatives
was then investigated. Results are summarized in Table 1 and
Figure 1. Given in Table 1 are results obtained from 1a, 3-
hexyne, and various amines. A significant variation of amines
could be applied to afford their corresponding indole deriva-
tives in good to excellent isolated yields. In addition to cyclic
secondary amines such as piperidine, morpholine, 4-methylpi-
peridine, 1-methylpiperazine, and 2-methylpiperidine (2a–e),
acyclic amines could also be used (2 f–h). Notably, besides sec-
ondary amines, primary amines such as aniline, tBuNH2, and
CyNH2 also showed good reactivity (2i–k).
Figure 1. Substrate scope: Various 2-amino iodobenzenes and alkynes.
Q=(CH2)5, Q’=(CH2)4
given in Table 1. Both alkyl and aryl alkynes could be used. Tri-
methylsilyl (TMS)-substituted unsymmetrical alkynes afforded
their corresponding products regioselectively with the TMS
group at the 2-position of the indole derivatives (2n,o). On the
Figure 1 shows results obtained from the reaction of piperi-
dine with various 2-amino iodobenzene derivatives 1 (1a–d)
and different alkynes by following the reaction conditions
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contrary, 1-phenyl-1-propyne gave a mixture of regioisomers
(2p,p’). It should be noted that when terminal alkynes were
used, formation of Sonogashira coupling products was ob-
served.[9] Compounds 1b,c with both electron-donating and
electron-withdrawing substituents showed good reactivity
(2q–s). Compound 1d with a five-membered azacycle could
be also used, thereby affording its corresponding indole deriv-
atives (2t,u) with a shorter bridge.
Application of N-ethyl indole derivatives for the synthesis of
benzosilolo[2,3-b]indole
The CÀN bond of cyclic amines in compounds 1 could be ef-
fectively cleaved and utilized for the synthesis of indole deriva-
tives 2. This reaction encouraged us to test acyclic amine-sub-
stituted iodobenzene derivatives such as 2-iodo-N,N-diethylani-
line (1e). Thus, as shown in Scheme 3, when the reaction of
Synthesis of N-substituted indole derivatives through four-
component coupling
When the reaction of 1-bromo-2-iodobenzene (3a) with 3-
hexyne and 2 molecules of piperidine was carried out under
the above reaction conditions, the indole derivative 2a was
obtained in 72% isolated yield (Table 2). It should be noted
Table 2. One-pot four-component coupling for the synthesis of indole
derivatives.
Scheme 3. Synthesis of N-alkyl indole derivatives and further application.
1e, alkyne, and piperidine was carried out under the above re-
action conditions, the N-ethyl indole derivative 4a was ob-
tained in 75% isolated yield. Different alkynes including alkyl,
aryl, and SiMe3-substituted ones could be used. Formation of
N-ethylpiperidine was observed by using GC analysis. It should
be noted that, in the absence of piperdine, only trace amounts
of 4 could be detected.
When (2-bromophenylethynyl)trimethylsilane was used as
the alkyne, its corresponding indole derivative 4d was isolated
in 77% yield. As a demonstration of the further application of
the products, product 4d was subjected to our previous reac-
tion conditions,[10c] and the benzosilolo[2,3-b]indole 5 was ob-
tained in 83% isolated yield.[10] Siloles are very important for
materials science.[11] The type of silole derivative 5 is not readily
available by other means.[10,12] This multicomponent coupling
process provides a good method for the synthesis of their pre-
cursors.
Mechanistic aspects
On the basis of the above observations and related litera-
ture,[8,13] possible reaction mechanisms are proposed and given
in Scheme 4. Thus, intermediate III would be formed from 1-(2-
iodophenyl)piperidine (1a) and alkyne by means of oxidative
addition followed by alkyne insertion,[13] whereas intermediate
IV would be formed through an oxidative addition/alkyne in-
sertion/amination/oxidative addition process with 1-bromo-2-
iodobenzene (3a), alkyne, and piperidine.[13] For cleavage of
the C(sp3)ÀN bond in intermediates III and IV, two possible
pathways are proposed with III as the example. Along path 1,
that when 1,2-dibromobenzene was used, no reaction took
place. As shown in Table 2, a one-pot four-component cou-
pling process was realized for the synthesis of N-substituted
indole derivatives. Compounds 3b,c with both electron-donat-
ing and electron-withdrawing substituents showed good reac-
tivity (2w–z). Highly selective formation of the products can
be rationalized by the higher reactivity of the CÀI bond than
the CÀBr bond, and the faster alkyne insertion reaction than
the amination reaction.
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the resulting indole derivative was demonstrated by the syn-
thesis of benzosilolo[2,3-b]indole.
Experimental Section
General methods
Unless otherwise noted, all starting materials were commercially
available and were used without further purification. Solvents were
purified using an Mbraun SPS-800 Solvent Purification System. All
reactions were carried out under a dry and oxygen-free nitrogen
atmosphere under slight positive pressure by using Schlenk tech-
niques. 1H and 13C NMR spectra were recorded using a Bruker
1
ARX400 spectrometer (FT, 400 MHz for H; 100 MHz for 13C) unless
otherwise noted. High-resolution mass spectra were recorded
using a Bruker Apex IV FTMS mass spectrometer using electrospray
ionization (ESI). GC analyses were recorded using a SHIMADZU GC-
2010 spectrometer using a flame-ionization detector (FID).
Typical procedure for the preparation of 2 or 4
Under an atmosphere of nitrogen, Pd(OAc)2 (2 mol%), L1
(5 mol%), and LiOtBu (1.5 mmol) were added to toluene (2 mL).
After this reaction mixture was stirred at room temperature for
5 min, compound 1 or 3 (0.5 mmol), alkyne (0.6 mmol), and amine
(2.5 mmol) were added, and this reaction mixture was stirred at
110 8C for 12 h. The reaction mixture was quenched with water
and extracted with Et2O. The extraction was washed with brine
and dried over MgSO4. The solvent was then evaporated under
vacuum, and the residue was purified by using a silica gel column
with petroleum ether and ethyl acetate as eluent to afford the final
products.
Compound 2a: Yellow oil, isolated in a yield of 86% (140 mg).
NMR spectroscopic data are consistent with the reported data.[8]
1
Compound 2b: Yellow oil, isolated yield of 87% (143 mg). H NMR
(400 MHz, CDCl3, Me4Si): d=1.18–1.25 (m, 6H; CH3), 1.34–1.42 (m,
2H; CH2), 1.47–1.55 (m, 2H; CH2), 1.72–1.80 (m, 2H; CH2), 2.29 (t,
J=7.5 Hz, 2H; CH2), 2.39 (brs, 4H; CH2), 2.70–2.77 (m, 4H; CH2),
3.69 (t, J=4.3 Hz, 4H; CH2), 4.03 (t, J=7.6 Hz, 2H; CH2), 7.05 (t, J=
7.3 Hz, 1H; CH), 7.12 (t, J=7.4 Hz, 1H; CH), 7.23 (d, J=8.0 Hz, 1H;
CH), 7.53 ppm (d, J=7.7 Hz, 1H; CH); 13C NMR (100 MHz, CDCl3,
Me4Si): d=15.3 (CH3), 16.1 (CH3), 17.7 (2CH2), 25.0 (CH2), 26.3 (CH2),
30.3 (CH2), 43.2 (CH2), 53.8 (2CH2), 58.8 (CH2), 67.0 (2CH2), 108.9
(CH), 112.8 (quat. C), 118.2 (CH), 118.4 (CH), 120.3 (CH), 127.7 (quat.
C), 135.8 (quat. C), 137.4 ppm (quat. C); HRMS: m/z calcd for
C21H33N2O [M+H]+: 329.2587; found: 329.2592.
Scheme 4. Proposed reaction mechanisms.
a direct cleavage of the C(sp3)ÀN bond to lead to intermediate
B would take place due to the coordination of the N atom to
the PdII center. In addition, formation of the aromatic indole
species B is also considered to be a driving force. However,
path 2, which involves intermediates D and E, could not be ex-
cluded. Detailed investigation into the reaction mechanism will
be carried out and will be reported in due course.
1
Compound 2c: Yellow oil, isolated yield of 85% (144 mg). H NMR
(400 MHz, CDCl3, Me4Si): d=0.91 (d, J=6.2 Hz, 3H; CH3), 1.18–1.41
(m, 11H; 2CH3 +2CH2 +CH), 1.50–1.62 (m, 4H; CH2), 1.72–1.80 (m,
2H; CH2), 1.83–1.89 (m, 2H; CH2), 2.27 (t, J=7.8 Hz, 2H; CH2), 2.70–
2.77 (m, 4H; CH2), 2.86 (d, J=11.6 Hz, 2H; CH2), 4.03 (t, J=7.7 Hz,
2H; CH2), 7.03–7.07 (m, 1H; CH), 7.12 (td, J=7.5 Hz, 1.1 Hz, 1H;
CH), 7.24 (d, J=8.5 Hz, 1H; CH), 7.53 ppm (d, J=7.7 Hz, 1H; CH);
13C NMR (100 MHz, CDCl3, Me4Si): d=15.3 (CH3), 16.1 (CH3), 17.7
(2CH2), 21.9 (CH2), 25.3 (CH3), 26.9 (CH2), 30.4 (CH2), 30.8 (CH2), 34.4
(2CH2), 43.2 (CH2), 54.2 (2CH2), 59.0 (CH2), 109.0 (CH), 112.7 (quat.
C), 118.2 (CH), 118.4 (CH), 120.3 (CH), 127.7 (quat. C), 135.8 (quat.
C), 137.5 ppm (quat. C); HRMS: m/z calcd for C23H37N2 [M+H]+:
341.2951; found: 341.2956.
Conclusion
In summary, we have developed an efficient synthetic method
for the synthesis of N-substituted indole derivatives by com-
bining a palladium-catalyzed multicomponent coupling pro-
cess with cleavage of C(sp3)ÀN bonds. Three or four compo-
nents of aryl iodides, alkynes, and amines were involved in this
coupling process. The cyclopentadiene–phosphine ligand
showed high efficiency. A variety of aryl iodides, including
cyclic and acyclic tertiary amino aryl iodides, and substituted 1-
bromo-2-iodobenzene derivatives could be used. Cyclic secon-
dary amines and acyclic amines including secondary and pri-
mary amines all showed good reactivity. Further application of
1
Compound 2d: Yellow oil, isolated yield of 84% (143 mg). H NMR
(400 MHz, CDCl3, Me4Si): d=1.18–1.25 (m, 6H; CH3), 1.33–1.41 (m,
2H; CH2), 1.49–1.56 (m, 2H; CH2), 1.72–1.80 (m, 2H; CH2), 2.30 (s,
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3H; CH3), 2.34 (t, J=7.7 Hz, 2H; CH2), 2.50 (brs, 8H; CH2), 2.70–2.77
(m, 4H; CH2), 4.03 (t, J=7.6 Hz, 2H; CH2), 7.04 (t, J=7.1 Hz, 1H;
CH), 7.12 (td, J=7.5 Hz, 1.0 Hz, 1H; CH), 7.23 (d, J=8.0 Hz, 1H;
CH), 7.53 ppm (d, J=7.7 Hz, 1H; CH); 13C NMR (100 MHz, CDCl3,
Me4Si): d=15.3 (CH3), 16.1 (CH3), 17.7 (2CH2), 25.1 (CH2), 26.4 (CH2),
30.3 (CH2), 43.1 (CH2), 45.8 (CH3), 52.8 (2CH2), 54.8 (2CH2), 58.2
(CH2), 109.0 (CH), 112.8 (quat. C), 118.2 (CH), 118.4 (CH), 120.3 (CH),
127.7 (quat. C), 135.8 (quat. C), 137.4 ppm (quat. C); HRMS: m/z
calcd for C22H36N3 [M+H]+: 342.2904; found: 342.2902.
7.5 Hz, 3H; CH3), 1.38–1.45 (m, 2H; CH2), 1.49–1.52 (m, 2H; CH2),
2.10 (brs, 1H; NH), 2.32 (t, J=7.2 Hz, 2H; CH2), 2.54 (q, J=7.5 Hz,
2H; CH2), 2.74 (q, J=7.51 Hz, 2H; CH2), 3.69 (t, J=7.5 Hz, 2H; CH2),
7.22–7.30 (m, 3H; CH), 7.66–7.68 ppm (m, 1H; CH); 13C NMR
(100 MHz, C6D6): d=15.5 (CH3), 16.5 (CH3), 17.9 (CH2), 18.1 (CH2),
24.9 (CH2), 28.2 (3 CH3), 29.9 (CH2), 30.5 (CH2), 42.0 (CH2), 43.1 (CH2),
51.7 (quat. C), 109.5 (CH), 113.2 (quat. C), 118.8 (CH), 119.1 (CH),
120.9 (CH), 128.6 (quat. C), 136.7 (quat. C), 137.2 ppm (quat. C);
HRMS: m/z calcd for C21H35N2 [M+H]+: 315.2795; found: 315.2794.
1
1
Compound 2e: Yellow oil, isolated yield of 91% (155 mg). H NMR
Compound 2k: Yellow oil, isolated yield of 61% (104 mg). H NMR
(400 MHz, CDCl3, Me4Si): d=1.04 (d, J=6.2 Hz, 3H; CH3), 1.18–1.25
(m, 6H; CH3), 1.28–1.37 (m, 4H; CH2), 1.49–1.66 (m, 6H; CH2), 1.72–
1.78 (m, 2H; CH2), 2.10 (td, J=11.1 Hz, 3.2 Hz, 1H; CH), 2.21–2.32
(m, 2H; CH2), 2.61–2.78 (m, 6H; CH2), 4.03 (t, J=7.7 Hz, 2H; CH2),
7.05 (td, J=7.4 Hz, 1.0 Hz, 1H; CH), 7.12 (td, J=7.5 Hz, 1.2 Hz, 1H;
CH), 7.24 (d, J=8.0 Hz, 1H; CH), 7.53 ppm (d, J=7.7 Hz, 1H; CH);
13C NMR (100 MHz, CDCl3, Me4Si): d=15.3 (CH3), 16.1 (CH3), 17.7
(2CH2), 19.2 (CH3), 24.1 (CH2), 25.3 (CH2), 25.4 (CH2), 26.2 (CH2), 30.4
(CH2), 34.7 (CH2), 43.2 (CH2), 52.3 (CH2), 54.0 (CH2), 55.9 (CH), 109.0
(CH), 112.8 (quat. C), 118.2 (CH), 118.4 (CH), 120.3 (CH), 127.7 (quat.
C), 135.8 (quat. C), 137.5 ppm (quat. C); HRMS: m/z calcd for
C23H37N2 [M+H]+: 341.2951; found: 341.2953.
(400 MHz, C6D6): d=1.04–1.30 (m, 16H; 2CH3 +5CH2), 1.46–1.54
(m, 3H; CH2 +NH), 1.65–1.68 (m, 2H; CH2), 1.76–1.79 (m, 2H; CH2),
2.25–2.32 (m, 1H; CH), 2.40 (t, J=6.8 Hz, 2H; CH2), 2.53 (q, J=
7.5 Hz, 2H; CH2), 2.74 (q, J=7.5 Hz, 2H; CH2), 3.68 (t, J=7.6 Hz, 2H;
CH2), 7.19–7.30 (m, 3H; CH), 7.68 ppm (d, J=7.1 Hz, 1H; CH);
13C NMR (100 MHz, C6D6): d=15.5 (CH3), 16.5 (CH3), 17.9 (CH2), 18.1
(CH2), 25.1 (CH2), 25.2 (2CH2), 26.7 (CH2), 30.6 (CH2), 30.7 (CH2), 34.0
(2CH2), 43.2 (CH2), 46.9 (CH2), 57.0 (CH), 109.4 (CH), 113.1 (quat. C),
118.8 (CH), 119.1 (CH), 120.9 (CH), 128.6 (quat. C), 136.7 (quat. C),
137.1 ppm (quat. C); HRMS: m/z calcd for C23H37N2 [M+H]+:
341.2951; found: 341.2954.
Compound 2l: Yellow oil, isolated yield of 92% (163 mg). NMR
Compound 2 f: Yellow oil, isolated yield of 85% (133 mg). NMR
spectroscopic data are consistent with the reported data.[8]
spectroscopic data are consistent with the reported data.[8]
1
Compound 2m: Yellow oil, isolated yield of 74% (156 mg). H NMR
1
Compound 2g: Yellow oil, isolated yield of 89% (133 mg). H NMR
(400 MHz, CDCl3, Me4Si): d=1.11–1.18 (m, 2H; CH2), 1.31–1.40 (m,
4H; CH2), 1.50–1.56 (m, 4H; CH2), 1.63–1.71 (m, 2H; CH2), 2.13 (t,
J=7.7 Hz, 2H; CH2), 2.26 (brs, 4H; CH2), 4.05 (t, J=7.6 Hz, 2H;
CH2), 7.10–7.41 (m, 13H; CH), 7.80 ppm (d, J=7.9 Hz, 1H; CH);
13C NMR (100 MHz, CDCl3, Me4Si): d=24.4 (CH2), 24.9 (CH2), 25.9
(2CH2), 26.4 (CH2), 29.8 (CH2), 43.7 (CH2), 54.6 (2CH2), 59.1 (CH2),
109.9 (CH), 115.2 (quat. C), 119.7 (CH), 120.0 (CH), 122.0 (CH), 125.3
(CH), 127.1 (quat. C), 128.0 (CH), 128.0 (2CH), 128.4 (2CH), 129.8
(2CH), 131.1 (2CH), 132.2 (quat. C), 135.2 (quat. C), 136.4 (quat. C),
137.4 ppm (quat. C); HRMS: m/z calcd for C30H35N2 [M+H]+:
423.2795; found: 423.2801.
(400 MHz, C6D6): d=0.97 (t, J=7.1 Hz, 3H; CH3), 1.05 (t, J=7.5 Hz,
3H; CH3), 1.12–1.17 (m, 2H; CH2), 1.25–1.29 (m, 5H; CH2 +CH3),
1.46–1.53 (m, 2H; CH2), 2.05 (s, 3H; CH3), 2.10 (t, J=7.0 Hz, 2H;
CH2), 2.24 (q, J=7.1 Hz, 2H; CH2), 2.52 (q, J=7.5 Hz, 2H; CH2), 2.74
(q, J=7.5 Hz, 2H; CH2), 3.67 (t, J=7.5 Hz, 2H; CH2), 7.18–7.29 (m,
3H; CH), 7.68 ppm (d, J=7.6 Hz, 1H; CH); 13C NMR (100 MHz, C6D6):
d=12.8 (CH3), 15.5 (CH3), 16.5 (CH3), 17.9 (CH2), 18.1 (CH2), 25.1
(CH2), 27.5 (CH2), 30.5 (CH2), 41.6 (CH3), 43.2 (CH2), 51.9 (CH2), 57.3
(CH2), 109.4 (CH), 113.1 (quat. C), 118.8 (CH), 119.1 (CH), 120.9 (CH),
128.6 (quat. C), 136.7 (quat. C), 137.1 ppm (quat. C); HRMS: m/z
calcd for C20H33N2 [M+H]+: 301.2638; found: 301.2630.
Compound 2n: Yellow oil, isolated yield of 93% (166 mg). NMR
spectroscopic data are consistent with the reported data.[8]
1
Compound 2h: Yellow oil, isolated yield of 89% (158 mg). H NMR
(400 MHz, C6D6): d=1.04–1.33 (m, 17H; 2CH3 +5CH2 +CH), 1.50–
1.56 (m, 2H; CH2), 1.70–1.74 (m, 4H; CH2), 2.12 (s, 3H; CH3), 2.23 (t,
J=6.9 Hz, 2H; CH2), 2.54 (q, J=7.5 Hz, 2H; CH2), 2.74 (q, J=7.5 Hz,
2H; CH2), 3.70 (t, J=7.6 Hz, 2H; CH2), 7.19–7.28 (m, 3H; CH), 7.65–
7.67 ppm (m, 1H; CH); 13C NMR (100 MHz, C6D6): d=15.5 (CH3),
16.5 (CH3), 17.9 (CH2), 18.2 (CH2), 25.0 (CH2), 26.4 (2CH2), 26.8 (CH2),
28.2 (CH2), 28.9 (2CH2), 30.6 (CH2), 37.5 (CH3), 43.3 (CH2), 53.4 (CH2),
63.3 (CH), 109.5 (CH), 113.1 (quat. C), 118.8 (CH), 119.1 (CH), 120.9
(CH), 128.6 (quat. C), 136.7 (quat. C), 137.1 ppm (quat. C); HRMS:
m/z calcd for C24H39N2 [M+H]+: 355.3108; found: 355.3107.
1
Compound 2o: Yellow oil, isolated yield of 69% (144 mg). H NMR
(400 MHz, CDCl3, Me4Si): d=0.15 (s, 9H; Si(CH3)3), 1.40–1.46 (m, 4H;
CH2), 1.55–1.63 (m, 6H; CH2), 1.85–1.93 (m, 2H; CH2), 2.29–2.37 (m,
6H; CH2), 4.25 (t, J=8.2 Hz, 2H; CH2), 7.03 (t, J=7.4 Hz, 1H; CH),
7.20–7.24 (m, 1H; CH), 7.33–7.38 ppm (m, 7H; CH); 13C NMR
(100 MHz, CDCl3, Me4Si): d=1.3 (3CH3), 24.5 (CH2), 25.3 (CH2), 26.0
(2CH2), 26.8 (CH2), 30.7 (CH2), 46.7 (CH2), 54.7 (2CH2), 59.3 (CH2),
109.3 (CH), 119.2 (CH), 119.8 (CH), 122.4 (CH), 126.6 (CH), 127.7
(2CH), 128.2 (quat. C), 129.3 (quat. C), 131.3 (2CH), 135.7 (quat. C),
137.1 (quat. C), 138.3 ppm (quat. C); HRMS: m/z calcd for
C27H39N2Si [M+H]+: 419.2877; found: 419.2883.
1
Compound 2i: Yellow oil, isolated yield of 75% (125 mg). H NMR
(400 MHz, C6D6): d=0.90–0.96 (m, 2H; CH2), 1.00–1.05 (m, 5H;
CH3 +CH2), 1.25 (t, J=7.5 Hz, 3H; CH3), 1.32–1.39 (m, 2H; CH2),
2.48 (q, J=7.5 Hz, 2H; CH2), 2.60 (t, J=6.6 Hz, 2H; CH2), 2.71 (q, J=
7.5 Hz, 2H; CH2), 2.91 (brs, 1H; NH), 3.58 (t, J=7.4 Hz, 2H; CH2),
6.40 (d, J=7.8 Hz, 2H; CH), 6.72 (t, J=7.3 Hz, 1H; CH), 7.12 (d, J=
5.8 Hz, 2H; CH), 7.17–7.27 (m, 3H; CH), 7.64 ppm (d, J=7.3 Hz, 1H;
CH); 13C NMR (100 MHz, C6D6): d=15.5 (CH3), 16.5 (CH3), 17.9 (CH2),
18.1 (CH2), 24.6 (CH2), 29.4 (CH2), 30.4 (CH2), 43.0 (CH2), 43.6 (CH2),
109.4 (CH), 112.9 (2CH), 113.2 (quat. C), 117.4 (CH), 118.9 (CH),
119.2 (CH), 120.9 (CH), 128.6 (quat. C), 129.5 (2CH), 136.7 (quat. C),
137.1 (quat. C), 148.8 ppm (quat. C); HRMS: m/z calcd for C23H31N2
[M+H]+: 335.2482; found: 335.2486.
Compound 2p/2p’: Yellow oil, combined isolated yield of 77%
(5:6) (139 mg) (the values in parentheses refer to the ratio of re-
gioisomers determined by GC). For 2p: 1H NMR (400 MHz, CDCl3,
Me4Si): d=1.03–1.14 (m, 2H; CH2), 1.25–1.41 (m, 4H; CH2), 1.52–
1.64 (m, 6H; CH2), 2.13 (t, J=7.8 Hz, 2H; CH2), 2.23 (s, 3H; CH3),
2.28 (brs, 4H; CH2), 4.01 (t, J=7.6 Hz, 2H; CH2), 7.13 (t, J=7.4 Hz,
1H; CH), 7.22 (t, J=7.5 Hz, 1H; CH), 7.33–7.49 (m, 6H; CH),
7.59 ppm (d, J=7.8 Hz, 1H; CH); 13C NMR (100 MHz, CDCl3, Me4Si):
d=9.2 (CH3), 24.4 (CH2), 24.9 (CH2), 25.9 (2CH2), 26.4 (CH2), 29.9
(CH2), 43.8 (CH2), 54.6 (2CH2), 59.2 (CH2), 108.7 (quat. C), 109.6 (CH),
118.9 (CH), 119.0 (CH), 121.5 (CH), 127.8 (CH), 128.4 (2CH), 128.6
(quat. C), 130.6 (2CH), 132.5 (quat. C), 136.3 (quat. C), 137.4 ppm
(quat. C). For 2p’: 1H NMR (400 MHz, CDCl3, Me4Si): d=1.37–1.44
(m, 4H; CH2), 1.52–1.61 (m, 6H; CH2), 1.77–1.85 (m, 2H; CH2), 2.28
1
Compound 2j: Yellow oil, isolated yield of 78% (122 mg). H NMR
(400 MHz, C6D6): d=1.03–1.15 (m, 14H; 4CH3 +CH2), 1.27 (t, J=
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(t, J=7.8 Hz, 2H; CH2), 2.36 (brs, 4H; CH2), 2.47 (s, 3H; CH3), 4.11 (t,
J=7.5 Hz, 2H; CH2), 7.09 (t, J=7.5 Hz, 1H; CH), 7.16–7.20 (m, 1H;
CH2), 7.27–7.32 (m, 2H; CH), 7.43–7.50 (m, 4H; CH), 7.65 ppm (d,
J=7.8 Hz, 1H; CH); 13C NMR (100 MHz, CDCl3, Me4Si): d=11.1 (CH3),
24.4 (CH2), 25.3 (CH2), 26.0 (2CH2), 26.7 (CH2), 30.1 (CH2), 43.4 (CH2),
54.7 (2CH2), 59.4 (CH2), 109.0 (CH), 114.1 (quat. C), 118.8 (CH), 119.5
(CH), 121.0 (CH), 125.6 (CH), 127.1 (quat. C), 128.4 (2CH), 129.8
(2CH2), 132.8 (quat. C), 135.8 (quat. C), 135.9 ppm (quat. C); HRMS:
m/z calcd for C25H33N2 [M+H]+: 361.2638; found: 361.2643.
(2CH2), 28.1 (CH2), 43.7 (CH2), 54.5 (2CH2), 58.5 (CH2), 110.0 (CH),
115.3 (quat. C), 119.7 (CH), 120.1 (CH), 122.0 (CH), 125.4 (CH), 127.2
(quat. C), 128.1 (3 CH), 128.4 (2CH), 129.8 (2CH), 131.1 (2CH), 132.3
(quat. C), 135.2 (quat. C), 136.4 (quat. C), 137.4 ppm (quat. C);
HRMS: m/z calcd for C29H33N2 [M+H]+: 409.2638; found: 409.2641.
Compound 2v: Yellow oil, isolated yield of 82% (135 mg). NMR
spectroscopic data are consistent with the reported data.[8]
1
Compound 2w: Yellow oil, isolated yield of 66% (117 mg). H NMR
(400 MHz, CDCl3, Me4Si): d=1.18–1.24 (m, 6H; CH3), 1.35–1.60 (m,
10H; CH2), 1.70–1.78 (m, 2H; CH2), 2.26 (t, J=7.8 Hz, 2H; CH2), 2.35
(brs, 4H; CH2), 2.67–2.75 (m, 4H; CH2), 3.86 (s, 3H; CH3), 3.99 (t, J=
7.7 Hz, 2H; CH2), 6.79 (dd, J=8.7 Hz, 2.5 Hz, 1H; CH), 7.00 (d, J=
2.4 Hz, 1H; CH), 7.13 ppm (d, J=8.8 Hz, 1H; CH); 13C NMR
(100 MHz, CDCl3, Me4Si): d=15.3 (CH3), 16.0 (CH3), 17.7 (CH2), 17.8
(CH2), 24.5 (CH2), 25.3 (CH2), 26.0 (2CH2), 26.7 (CH2), 30.5 (CH2), 43.3
(CH2), 54.7 (2CH2), 56.1 (CH3), 59.4 (CH2), 100.7 (CH), 109.6 (CH),
110.0 (CH), 112.4 (quat. C), 127.9 (quat. C), 131.2 (quat. C), 138.3
(quat. C), 153.5 ppm (quat. C); HRMS: m/z calcd for C23H37N2O
[M+H]+: 357.2900; found: 357.2903.
1
Compound 2q: Yellow oil, isolated yield of 92% (156 mg). H NMR
(400 MHz, CDCl3, Me4Si): d=1.17–1.24 (m, 6H; CH3), 1.33–1.44 (m,
4H; CH2), 1.50–1.60 (m, 6H; CH2), 1.70–1.78 (m, 2H; CH2), 2.25 (t,
J=7.8 Hz, 2H; CH2), 2.34 (brs, 4H; CH2), 2.44 (s, 3H; CH3), 2.67–2.75
(m, 4H; CH2), 3.99 (t, J=7.7 Hz, 2H; CH2), 6.94 (dd, J=7.0 Hz,
1.3 Hz, 1H; CH), 7.12 (d, J=8.3 Hz, 1H; CH), 7.31 ppm (s, 1H; CH);
13C NMR (100 MHz, CDCl3, Me4Si): d=15.3 (CH3), 16.1 (CH3), 17.7
(CH2), 17.7 (CH2), 21.5 (CH3), 24.5 (CH2), 25.3 (CH2), 26.0 (2CH2), 26.7
(CH2), 30.4 (CH2), 43.2 (CH2), 54.7 (2CH2), 59.4 (CH2), 108.7 (CH),
112.2 (quat. C), 118.0 (CH), 121.8 (CH), 127.5 (quat. C), 127.9 (quat.
C), 134.3 (quat. C), 137.6 ppm (quat. C); HRMS: m/z calcd for
C23H37N2 [M+H]+: 341.2951; found: 341.2953.
1
Compound 2x: Yellow oil, isolated yield of 74% (126 mg). H NMR
(400 MHz, CDCl3, Me4Si): d=1.17–1.24 (m, 6H; CH3), 1.33–1.44 (m,
4H; CH2), 1.51–1.61 (m, 6H; CH2), 1.71–1.79 (m, 2H; CH2), 2.27 (t,
J=7.8 Hz, 2H; CH2), 2.35 (brs, 4H; CH2), 2.47 (s, 3H; CH3), 2.67–2.75
(m, 4H; CH2), 3.99 (t, J=7.8 Hz, 2H; CH2), 6.88 (d, J=7.9 Hz, 1H;
CH), 7.02 (s, 1H; CH), 7.41 ppm (d, J=8.0 Hz, 1H; CH); 13C NMR
(100 MHz, CDCl3, Me4Si): d=15.3 (CH3), 16.1 (CH3), 17.6 (CH2), 17.7
(CH2), 21.8 (CH3), 24.5 (CH2), 25.3 (CH2), 26.0 (2CH2), 26.7 (CH2), 30.3
(CH2), 43.1 (CH2), 54.7 (2CH2), 59.4 (CH2), 109.0 (CH), 112.5 (quat. C),
117.9 (CH), 120.0 (CH), 125.6 (quat. C), 130.0 (quat. C), 136.2 (quat.
C), 136.7 ppm (quat. C); HRMS: m/z calcd for C23H37N2 [M+H]+:
341.2951; found: 341.2960.
1
Compound 2r: Yellow oil, isolated yield of 83% (182 mg). H NMR
(400 MHz, CDCl3, Me4Si): d=1.11–1.18 (m, 2H; CH2), 1.31–1.41 (m,
4H; CH2), 1.52–1.58 (m, 4H; CH2), 1.62–1.70 (m, 2H; CH2), 2.14 (t,
J=7.8 Hz, 2H; CH2), 2.28 (brs, 4H; CH2), 2.46 (s, 3H; CH3), 4.05 (t,
J=7.6 Hz, 2H; CH2), 7.09–7.16 (m, 2H; CH), 7.22–7.37 (m, 10H; CH),
7.57 ppm (s, 1H; CH); 13C NMR (100 MHz, CDCl3, Me4Si): d=21.5
(CH3), 24.4 (CH2), 25.0 (CH2), 25.9 (2CH2), 26.4 (CH2), 29.9 (CH2), 43.8
(CH2), 54.6 (2CH2), 59.2 (CH2), 109.6 (CH), 114.9 (quat. C), 119.3 (CH),
123.5 (CH), 125.3 (CH), 127.4 (quat. C), 128.0 (CH), 128.1 (2CH),
128.4 (2CH), 129.4 (quat. C), 129.9 (2CH), 131.1 (2CH), 132.4 (quat.
C), 134.8 (quat. C), 135.4 (quat. C), 137.6 ppm (quat. C); HRMS: m/z
calcd for C31H37N2 [M+H]+: 437.2951; found: 437.2959.
1
Compound 2y: Yellow oil, isolated yield of 58% (100 mg). H NMR
(400 MHz, C6D6): d=1.00 (t, J=7.6 Hz, 3H; CH3), 1.21 (t, J=7.4 Hz,
3H; CH3), 1.33–1.42 (m, 8H; CH2), 1.49–1.55 (m, 4H; CH2), 2.07 (t,
J=7.2 Hz, 2H; CH2), 2.22 (brs, 4H; CH2), 2.44 (q, J=7.5 Hz, 2H;
CH2), 2.63 (q, J=7.6 Hz, 2H; CH2), 3.51 (t, J=7.6 Hz, 2H; CH2), 6.95–
7.00 (m, 2H; CH), 7.33–7.37 ppm (m, 1H; CH); 13C NMR (100 MHz,
C6D6): d=15.4 (CH3), 16.4 (CH3), 17.9 (CH2), 18.0 (CH2), 25.0 (CH2),
25.0 (CH2), 26.5 (2CH2), 26.9 (CH2), 30.2 (CH2), 43.3 (CH2), 55.0
(2CH2), 59.1 (CH2), 96.1 (d, J=25.7 Hz, CH), 107.3 (d, J=24.0 Hz,
CH), 113.2 (quat. C), 119.4 (d, J=10.1 Hz, CH), 125.0 (quat. C), 136.6
(d, J=11.6 Hz, quat. C), 137.6 (d, J=3.7 Hz, quat. C), 160.1 ppm (d,
J=233.7 Hz, quat. C); HRMS: m/z calcd for C22H34FN2 [M+H]+:
345.2701; found: 345.2708.
1
Compound 2s: Yellow oil, isolated yield of 90% (155 mg). H NMR
(400 MHz, CDCl3, Me4Si): d=1.20 (td, J=7.6 Hz, 2.6 Hz, 6H; CH3),
1.31–1.43 (m, 4H; CH2), 1.48–1.60 (m, 6H; CH2), 1.70–1.77 (m, 2H;
CH2), 2.25 (t, J=7.8 Hz, 2H; CH2), 2.33 (brs, 4H; CH2), 2.64–2.76 (m,
4H; CH2), 4.00 (t, J=7.7 Hz, 2H; CH2), 6.84 (td, J=9.1 Hz, 2.5 Hz,
1H; CH), 7.10–7.17 ppm (m, 2H; CH); 13C NMR (100 MHz, CDCl3,
Me4Si): d=15.2 (CH3), 15.9 (CH3), 17.6 (CH2), 17.8 (CH2), 24.5 (CH2),
25.3 (CH2), 26.0 (2CH2), 26.7 (CH2), 30.4 (CH2), 43.4 (CH2), 54.7
(2CH2), 59.3 (CH2), 103.1 (d, J=22.8 Hz, CH), 108.3 (d, J=26.0 Hz,
CH), 109.4 (d, J=9.6 Hz, CH), 112.8 (d, J=4.5 Hz, quat. C), 127.9 (d,
J=9.3 Hz, quat. C), 132.4 (quat. C), 139.3 (quat. C), 157.5 ppm (d,
J=231.7 Hz, quat. C); HRMS: m/z calcd for C22H34FN2 [M+H]+:
345.2701; found: 345.2700.
1
Compound 2z: Yellow oil, isolated yield of 62% (112 mg). H NMR
(400 MHz, C6D6): d=0.98 (t, J=7.4 Hz, 3H; CH3), 1.18 (t, J=7.6 Hz,
3H; CH3), 1.26–1.39 (m, 8H; CH2), 1.49–1.55 (m, 4H; CH2), 2.06 (t,
J=7.2 Hz, 2H; CH2), 2.22 (brs, 4H; CH2), 2.42 (q, J=7.6 Hz, 2H;
CH2), 2.60 (q, J=7.5 Hz, 2H; CH2), 3.49 (t, J=7.6 Hz, 2H; CH2), 7.19–
7.21 (m, 1H; CH), 7.31–7.34 ppm (m, 2H; CH); 13C NMR (100 MHz,
C6D6): d=15.2 (CH3), 16.3 (CH3), 17.8 (CH2), 17.9 (CH2), 25.0 (CH2),
26.5 (2CH2), 26.9 (CH2), 30.2 (CH2), 30.3 (CH2), 43.3 (CH2), 55.0
(2CH2), 59.1 (CH2), 109.6 (CH), 113.3 (quat. C), 119.6 (CH), 119.6
(CH), 127.0 (quat. C), 127.0 (quat. C), 137.0 (quat. C), 138.1 ppm
(quat. C); HRMS: m/z calcd for C22H34ClN2 [M+H]+: 361.2405;
found: 361.2412.
1
Compound 2t: Yellow oil, isolated yield of 70% (109 mg). H NMR
(400 MHz, CDCl3, Me4Si): d=1.19–1.25 (m, 6H; CH3), 1.36–1.43 (m,
2H; CH2), 1.54–1.60 (m, 6H; CH2), 1.71–1.79 (m, 2H; CH2), 2.28–2.35
(m, 6H; CH2), 2.70–2.78 (m, 4H; CH2), 4.05 (t, J=7.7 Hz, 2H; CH2),
7.04 (t, J=7.3 Hz, 1H; CH), 7.12 (t, J=7.3 Hz, 1H; CH), 7.26 (d, J=
8.1 Hz, 1H; CH), 7.53 ppm (d, J=7.8 Hz, 1H; CH); 13C NMR
(100 MHz, CDCl3, Me4Si): d=15.3 (CH3), 16.1 (CH3), 17.7 (2CH2), 24.5
(CH2), 24.5 (CH2), 26.0 (2CH2), 28.5 (CH2), 43.1 (CH2), 54.6 (2CH2),
58.8 (CH2), 109.0 (CH), 112.8 (quat. C), 118.2 (CH), 118.4 (CH), 120.3
(CH), 127.7 (quat. C), 135.9 (quat. C), 137.5 ppm (quat. C); HRMS:
m/z calcd for C21H33N2 [M+H]+: 313.2638; found: 313.2643.
1
Compound 4a: Yellow oil, isolated yield of 75% (75 mg). NMR
Compound 2u: Yellow oil, isolated yield of 57% (116 mg). H NMR
spectroscopic data are consistent with the reported data.[8]
(400 MHz, CDCl3, Me4Si): d=1.34–1.39 (m, 4H; CH2), 1.50–1.56 (m,
4H; CH2), 1.64–1.72 (m, 2H; CH2), 2.12–2.25 (m, 6H; CH2), 4.09 (t,
J=7.7 Hz, 2H; CH2), 7.12–7.16 (m, 2H; CH), 7.27–7.37 (m, 10H; CH),
7.44 (d, J=8.2 Hz, 1H; CH), 7.79 ppm (d, J=7.9 Hz, 1H; CH);
13C NMR (100 MHz, CDCl3, Me4Si): d=24.2 (CH2), 24.4 (CH2), 25.9
1
Compound 4b: Yellow oil, isolated yield of 95% (141 mg). H NMR
(400 MHz, CDCl3, Me4Si): d=1.26 (t, J=7.2 Hz, 3H; CH3), 4.11 (q, J=
7.2 Hz, 2H; CH2), 7.12–7.36 (m, 12H; CH), 7.42 (d, J=8.2 Hz, 1H;
CH), 7.81 ppm (d, J=8.0 Hz, 1H; CH); 13C NMR (100 MHz, CDCl3,
Chem. Eur. J. 2014, 20, 2605 – 2612
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78; h) C. F. Nising, Chem. Soc. Rev. 2010, 39, 591–599; i) M. Ishikura, T.
Abe, T. Choshi, S. Hibino, Nat. Prod. Rep. 2013, 30, 694–752.
Me4Si): d=15.4 (CH3), 38.6 (CH2), 109.8 (CH), 115.3 (quat. C), 119.8
(CH), 120.1 (CH), 122.0 (CH), 125.4 (CH), 127.3 (quat. C), 128.1 (CH),
128.1 (2CH), 128.4 (2CH), 129.8 (2CH), 131.1 (2CH), 132.3 (quat. C),
135.2 (quat. C), 136.1 (quat. C), 137.3 ppm (quat. C); HRMS: m/z
calcd for C22H20N [M+H]+: 298.1590; found: 298.1595.
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Sundberg, Indoles, Academic Press, New York, 1996; b) E. Arzel, P.
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sais, A. Godard, G. Quꢁguiner, J. Med. Chem. 2001, 44, 949–960; c) P.
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G. L. Firestone, Proc. Natl. Acad. Sci. USA 2008, 105, 19750–19755;
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C. Inglese, F. Berardi, R. Perrone, J. Med. Chem. 2007, 50, 4648–4655.
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Soc. Perkin Trans. 1 2000, 1045–1075; b) T. L. Gilchrist, J. Chem. Soc.
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Cacchi, G. Fabrizi, Chem. Rev. 2005, 105, 2873–2920; c) L. Ackermann,
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Compound 4c: Yellow oil, isolated yield of 86% (99 mg). NMR
spectroscopic data are consistent with the reported data.[8]
1
Compound 4d: Yellow oil, isolated yield of 77% (143 mg). H NMR
(400 MHz, C6D6): d=0.15 (s, 9H; CH3), 1.08 (t, J=7.1 Hz, 3H; CH3),
3.91 (q, J=7.1 Hz, 2H; CH2), 6.80 (td, J=7.7 Hz, 1.7 Hz, 1H; CH),
6.92–6.96 (m, 1H; CH), 7.08–7.13 (m, 2H; CH), 7.21–7.25 (m, 2H;
CH), 7.36 (d, J=8.0 Hz, 1H; CH), 7.52 ppm (dd, J=8.0 Hz, 0.8 Hz,
1H; CH); 13C NMR (100 MHz, C6D6): d=0.5 (3 CH3), 15.6 (CH3), 41.1
(CH2), 109.7 (CH), 119.9 (CH), 120.5 (CH), 122.8 (CH), 126.8 (CH),
128.9 (CH), 129.8 (quat. C), 132.6 (CH), 133.0 (quat. C), 133.0 (CH),
133.8 (quat. C), 135.5 (quat. C), 138.6 (quat. C), 139.1 ppm (quat. C);
HRMS: m/z calcd for C19H23BrNSi [M+H]+: 372.0778; found:
372.0788.
Typical procedure for the preparation of benzosilolo[2,3-
b]indole (5)
Under a nitrogen atmosphere, [PdCl(p-allyl)] (2.5 mol%) and P(tBu)3
(10 mol%) were added to toluene (2 mL). After this reaction mix-
ture was stirred at room temperature for 15 min, compound 4d
(0.3 mmol), LiOtBu (0.9 mmol), and 4-nitrobenzaldehyde (0.3 mmol)
were added and this reaction mixture was stirred at 1208C for
24 h.[9d] The reaction mixture was quenched with water and ex-
tracted with Et2O. The extraction was washed with brine and dried
over MgSO4. The solvent was then evaporated under vacuum, and
the residue was purified by using a silica gel column with petro-
leum ether and ethyl acetate as eluent to afford the final product
5.
Benzosilolo[2,3-b]indole (5): Colorless oil, isolated yield of 83%
1
(69 mg). H NMR (400 MHz, CDCl3, Me4Si): d=0.51 (s, 6H; CH3), 1.47
(t, J=7.3 Hz, 3H; CH3), 4.21 (q, J=7.27, 2H; CH2), 7.06–7.10 (m, 1H;
CH), 7.15–7.25 (m, 2H; CH), 7.34–7.40 (m, 2H; CH), 7.46 (d, J=
7.0 Hz, 1H; CH), 7.74 (d, J=7.6 Hz, 1H; CH), 7.98 ppm (d, J=7.7 Hz,
1H; CH); 13C NMR (100 MHz, CDCl3, Me4Si): d=À3.34 (2CH3), 16.06
(CH3), 42.34 (CH2), 109.99 (CH), 119.83 (CH), 120.16 (CH), 120.19
(CH), 122.11 (CH), 124.10 (CH), 124.33 (quat. C), 130.27 (CH), 131.52
(quat. C), 132.39 (CH), 138.06 (quat. C), 141.73 (quat. C), 143.90
(quat. C), 145.64 ppm (quat. C); HRMS: m/z calcd for C18H20NSi
[M+1]+: 278.1360; found: 278.1354.
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Acknowledgements
This work was supported by the 973 Program (2012CB821600)
and the Natural Science Foundation of China (NSFC).
Keywords: cleavage reactions · indoles · multicomponent
reactions · palladium · synthetic methods
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Received: October 29, 2013
Published online on January 21, 2014
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