One-pot multicomponent synthesis of azaindoles and pyrroles from one molecule of a silicon-tethered diyne and three or two molecules of organonitriles mediated by zirconocene

Article abstract of DOI:10.1002/chem.200902411

A zirconocene-mediated one-pot multicomponent synthesis process leading to the synthesis of pyrrolo[3,2-c]pyridine (5-azaindoles) and pyrrole derivatives has been developed starting from a silicon-tethered diyne and three or two different or identical org

Full text of DOI:10.1002/chem.200902411

DOI: 10.1002/chem.200902411
One-Pot Multicomponent Synthesis of Azaindoles and Pyrroles from One
Molecule of a Silicon-Tethered Diyne and Three or Two Molecules of
Organonitriles Mediated by Zirconocene
Shaoguang Zhang,[a] Xiaohua Sun,[a, b] Wen-Xiong Zhang,[a] and Zhenfeng Xi*[a, c]
12608
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Chem. Eur. J. 2009, 15, 12608 – 12617

FULL PAPER
Abstract:
A
zirconocene-mediated
have been highly selectively prepared
by this protocol. A wide variety of or-
-donating groups, have been used to
afford 5-azaindoles and/or pyrroles in
good-to-excellent isolated yields. A key
intermediate formed in the Cp2ZrII-
mediated reaction of one (PhCꢀ
C)2SiMe2, two molecules of iPrCN and
one p-tolylCN was characterised by X-
ray single-crystal structural analysis,
which has allowed us to gain a good
understanding of the reaction process.
one-pot multicomponent synthesis pro-
cess leading to the synthesis of pyrrolo-
ganonitriles
and
silicon-tethered
A
diynes, either aliphatic or aromatic
with both electron-withdrawing and
role derivatives has been developed
starting from a silicon-tethered diyne
and three or two different or identical
organonitriles.
and pyrrole derivatives with diverse
structures and substitution patterns
Keywords: alkynes
·
cyanides
·
PyrroloACTHNGUTERN[UNG 3,2-c]pyridine
multicomponent reactions · nitro-
gen heterocycles · zirconium
Introduction
tallic chemistry, particularly transition-metal-mediated or
-catalysed reactions and lithiation approaches, have greatly
contributed to the development of azaindole synthesis and
azaindole chemistry.[1a] In addition, the development of syn-
thetically useful methods for the preparation of pyrrole de-
rivatives has continuously been a major research topic in
synthetic chemistry[6,7] because they are of great importance
in many areas.[6–8]
Pyrrolopyridines (azaindoles, Figure 1) are a class of hetero-
ACHTUNGTRENNUNG
We recently reported zirconocene-mediated intermolecu-
lar coupling reactions of one molecule of a silicon-tethered
diyne with three molecules of organonitriles, which afforded
Figure 1. Structures of azaindoles. I: 7-azaindole or pyrrolo
dine; II: 6-azaindole or pyrrolo[2,3-c]pyridine; III: 5-azaindole or
pyrrolo[3,2-c]pyridine; IV: 4-azaindole or pyrrolo[3,2-b]pyridine.
ACHTUNGTREN[NUNG 2,3-b]pyri-
pyrroloACHTNUTRGNE[NUG 3,2-c]pyridine derivatives (5-azaindole, type III in
AHCTUNGTRENNUNG
Figure 1) by an unexpected reaction mechanism
G
ACHTUNGTRENNUNG
(Scheme 1).[9] This multicomponent one-pot process integra-
thesis and as indole bioisosteres in the design of biologically
active compounds.[1–3] However, the synthesis of azaindoles
has remained a challenge for synthetic chemists both in aca-
demia and in the pharmaceutical industry because the clas-
sic methods for the synthesis of indole derivatives and relat-
ed N-containing heterocycles do not work well in the syn-
thesis of azaindole analogues, or at least, they work but not
efficiently.[1–5] In recent years, strategies applying organome-
[a] S. Zhang,+ Dr. X. Sun,+ 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 the Ministry of Education
College of Chemistry, Peking University
Beijing 100871 (China)
Scheme 1. Multicomponent synthesis of 5-azaindoles from one molecule
of a silicon-tethered diyne with three molecules of organonitriles mediat-
ed by zirconocene.
Fax : (+86)-10-62751708
E-mail: zfxi@pku.edu.cn
[b] Dr. X. Sun+
tes four molecules into the final product and represents a
synthetically useful method for the preparation of otherwise
unavailable but very important pyrrolo
atives.[10] We envisioned that more diverse structures of
pyrrolo[3,2-c]pyridine derivatives with different substitution
patterns could be prepared by following this protocol. Thus,
we started to investigate the scope and limitations of this
procedure. Indeed, we found that a wide variety of organo-
nitriles, either aliphatic or aromatic with both electron-with-
drawing and -donating groups, could be used to afford 5-
azaindoles in good-to-excellent isolated yields. Pyrrole de-
ACHTUNGERTN[NUNG 3,2-c]pyridine deriv-
Institute of Chemistry, Chinese Academy of Sciences
Beijing 100190 (China)
[c] Prof. Dr. Z. Xi
AHCTUNGTRENNUNG
State Key Laboratory of Organometallic Chemistry
Shanghai Institute of Organic Chemistry
Chinese Academy of Sciences
Shanghai 200032 (China)
[+] Mr. S. Zhang and Dr. X. Sun contributed equally to this work.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.200902411.
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Z. Xi et al.
rivatives with all different substituents could also be synthes-
ised depending on the organonitriles used.
Results and Discussion
Formation of 5-azaindoles from one molecule of a silicon-
tethered diyne with three molecules of the same organoni-
trile: Zirconocene(II) species, which have been proven to be
very useful organometallic intermediates,[11] can be easily
generated in situ from [Cp2ZrBu2] (Negishi reagent) or
[Cp2ZrEt2] (Takahashi reagent).[12] As we have previously
communicated,[9] zirconocene-mediated intermolecular cou-
pling reactions of one molecule of a silicon-tethered diyne
with three molecules of the same organonitrile take place to
afford pyrroloACHTUNGTRENNUNG[3,2-c]pyridine derivatives upon hydrolysis
(Scheme 2). Further investigations have revealed that a
wide variety of silicon-tethered diynes and organonitriles,
especially functionalised ones, can be used in this procedure
to afford pyrroloACHTUNGTRENNUNG[3,2-c]pyridine derivatives with diverse sub-
stitution patterns. Listed in Scheme 2 are the results of reac-
tions performed with either aromatic or aliphatic organoni-
tiriles. In most cases the products are formed in high isolat-
ed yields. Three examples (1a, 1b and 1k, each formed
from 2a) previously communicated are also listed in
Scheme 2 for comparison.[9b]
A variety of bis(arylalkynyl)silanes 2 could act as suitable
components. In addition to phenyl-substituted alkynes (2a–
c), we also investigated the following substituted or func-
tionalised bis(arylalkynyl)silanes: 4-Me (2d), 4-MeO (2e),
4-Br (2 f) and 4-CF3 (2g).[13]
We found that, in addition to 2a–c, the silicon-tethered
diynes 2d–g with functional substituents also gave good re-
sults, leading to the formation of azaindoles bearing various
functional groups. Electron-donating MeO and -withdrawing
CF3 groups on the aryl moiety of 2 also afforded the corre-
sponding multifunctionalised azaindoles (1 f–h) in moderate-
to-good yields. Note that the bromine atoms in 2 f survived
the zircocene-mediated conditions to give the azaindoles
1d,e in good yields.
Scheme 2. Formation of pyrroloACTHNUGRTENUNG[3,2-c]pyridine derivatives from one sili-
con-tethered diyne (2a–g) and three identical organonitriles (R1CN).
Silicon-tethered diynes 2 with different steric hindrances
at the silicon centre were also investigated in this reaction.
Changing the substituents at the silicon centre in 2 from
methyl to ethyl clearly lowered the reaction rate and also
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Multicomponent Synthesis of Azaindoles and Pyrroles
FULL PAPER
gave lower yields. For example, the 48% yield of 1a from
Et2Si-tethered diyne 2b is markedly lower than the yield of
70% obtained from Me2Si-tethered diyne 2a. Notably, when
the Ph2Si-tethered diyne 2c was used in this reaction, only
trace amounts of the product were obtained even under
reflux conditions. This finding indicated that this zircono-
cene-mediated multicomponent coupling reaction is very
sensitive towards the bulkiness of the components of 2.
A wide variety of organonitriles, either aliphatic or aro-
matic with both electron-withdrawing and -donating groups,
could be used to afford 5-azaindoles in good isolated yields.
Heterocyclic nitriles such as thiophene-2-nitrile gave rise to
the fully substituted azaindoles (1i,j). Functionalised groups
on the aromatic nitriles were tolerated in this process, al-
though slightly lower yields were gained in comparison with
PhCN. The 4-Me (1b), 3-Me (1 f), 4-MeO (1e, 1g) and 3-Br
(1h, 1o) substituted benzonitriles all gave good results.
When the somewhat sterically hindered o-tolunitrile was
used, the reaction smoothly gave the o-tolyl-substituted
azaindole 1c in a yield of 62%. However, other functional-
ised or sterically hindered nitriles, for example, 2-cyanopyri-
dine, 9-cyanophenathracene and 2-bromobenzonitrile, only
gave trace amounts of the azaindoles.
and efficiently prepare substituted pyrroles 3. The use of
1.5 equiv of 2-methylbutyronitrile cleanly led to the forma-
tion of pyrroles 3b,c under conditions similar to those used
previously (Table 1), with the corresponding 5-azaindole de-
Table 1. Formation of pyrroles bearing all different substituents
Si-tethered
Organonitrile
Product 3
Isolated
diyne 2
yield [%]
2d
2a
2d
3a: 46
3b: 50
3c: 40
The azaindoles functionalised with bromine could be fur-
ther transformed into more complicated and diverse azain-
doles. Thus, subjecting the bromine-bearing azaindoles 1n
and 1o to Suzuki coupling conditions with benzeneboronic
acid gave the corresponding arylated azaindoles 1p and 1q
in yields of 53 and 82%, respectively (see Scheme 3).[14,15]
2a
3d: 53
rivatives not being detected. Interestingly, the bulkier 1-
cyano-1-phenylcyclopropane could also be used to stop the
reaction halfway to give the pyrrole 3d as the sole product
in a yield of 53%, even when 5.0 equiv of 1-cyano-1-phenyl-
cyclopropane were used under the present conditions.
These pyrrole derivatives, which have all different sub-
stituents, are difficult to access by other methods and may
have interesting properties because of their unique structure
and substitution patterns.
Formation of 5-azaindoles from one molecule of a silicon-
tethered diyne, two molecules of the same organonitrile and
a different organonitrile: Because organonitriles such as
iPrCN and 2-methylbutyronitrile can stop the reaction after
two molecules of iPrCN or 2-methylbutyronitriles have been
incorporated into the organometallic intermediate, we had
an opportunity to integrate two different organonitriles into
Scheme 3. Further reactions of the 5-azaindoles: Suzuki coupling reac-
tions.
Formation of pyrroles from one molecule of a silicon-teth-
ered diyne and two molecules of the same organonitrile: It
was previously found that iPrCN, a relatively bulky organo-
nitrile, could stop the above reaction involving two mole-
cules of organonitriles midway to give multisubstituted pyr-
roles upon hydrolysis of the reaction mixtures.[9] Inspired by
this finding, we searched for a variety of organonitriles with
appropriate steric hindrance to stop the reaction midway
the pyrrolo
ACHTUNGTRENNUNG
in Scheme 4, a variety of pyrroloAHCNUTGTRENNUNG
assembled from one silicon-tethered diyne, two molecules of
iPrCN and one molecule of another organonitrile can be
readily obtained in good isolated yields with excellent
chemo- and regioselectivity. The second organonitrile
(R2CN) as the fourth component could be either aromatic
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Z. Xi et al.
cules of iPrCN, one molecule of p-tolylCN and one Cp2Zr
species: To gain an in-depth understanding of the mecha-
nism of this zirconocene-mediated multicomponent synthe-
sis of azaindoles with perfect chemo- and regioselectivity,
we successfully isolated the key intermediate formed in the
Cp2ZrII-mediated reaction of one (PhCꢀC)2SiMe2, two mol-
ecules of iPrCN and one molecule of a different organoni-
trile, p-tolylCN. The azazirconacyclobutane-containing inter-
mediate 5 was isolated directly from the reaction of 2a with
1.5 equiv of iPrCN mediated by [Cp2ZrBu2] in toluene solu-
tion (Scheme 5).[9,16] Treatment of a benzene solution of 5
Scheme 4. Formation of pyrroloACTHNUGRTENUNG[3,2-c]pyridine derivatives from one sili-
con-tethered diyne and three molecules of two different organonitriles.
or aliphatic. The structures of 4a and 4c were determined
by single-crystal X-ray structural analysis (Figure 2).
Scheme 5. Isolation of the key intermediate 6.
Isolation and structural analysis of the key intermediate
composed of one molecule of (PhCꢀC)2SiMe2, two mole-
with p-tolylCN at 508C for 1 h gave a deep-brown solution,
which was dried under vacuum and then crystallised in a
THF/hexane mixed solvent to afford the complex 6 as
brown crystals in an isolated yield of 90%. Single-crystal X-
ray structural analysis of 6 (Figure 3) clearly showed a
three-ring-fused skeleton containing the Me2Si and Cp2Zr
moieties.
Figure 3. ORTEP drawing of 6 with 30% thermal ellipsoids. Hydrogen
À
atoms have been omitted for clarity. Selected bond lengths [ꢁ]: Zr1 N1
À
À
À
À
2.015(3), Zr1 N2 2.244(3), Si1 N3 1.744(3), Si1 C27 1.934(3), C5 C27
À
À
À
À
Figure 2. ORTEP drawings of 4a (top) and 4c (bottom) with 30% ther-
mal ellipsoids. Hydrogen atoms have been omitted for clarity.
1.550(4), C5 C39 1.403(5), C23 C42 1.379(5), C27 C32 1.532(4), C37
À
À
À
C39 1.438(9), C39 C42 1.446(4), N1 C32 1.260(4), N3 C37 1.291(4).
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Multicomponent Synthesis of Azaindoles and Pyrroles
FULL PAPER
was added dropwise through a syringe to a toluene (10 mL) solution of
[Cp2ZrCl2] (1.05 mmol, 307 mg) at À788C (dry ice/acetone) in a 20 mL
Schlenk tube. After the addition was complete, the reaction mixture was
stirred at À788C for 1 h. Then bis(phenylethynyl)dimethylsilane (2a;
1 mmol) was added and the reaction mixture was warmed up to 508C
and stirred at this temperature for 3 h. Benzonitrile (3.5 mmol, 361 mg)
was then added and the reaction mixture was stirred at this temperature
for 1 h. The reaction mixture was quenched with a saturated aqueous so-
lution of NaHCO3 and the resulting mixture was extracted with diethyl
ether three times then washed with water and brine. The extract was
dried over anhydrous MgSO4. The solvent was evaporated in vacuo to
give a yellow solid, which was subjected to SiO2 column chromatography
using hexane and diethyl ether (10:1) as the eluent. The characterisation
data for compounds 1a, 1b, 1i and 1k have been published in our previ-
ous communication.[9b]
The two imine moieties adjacent to the silicon and zirco-
nium atoms originated from iPrCN and p-tolylCN, respec-
tively, which supports the mechanism previously proposed in
which the unsaturated CꢀN bond of p-tolylCN as the third
À
nitrile molecule selectively inserts into the C ZrCp2 bond of
the azazirconacyclobutane moiety in 5.[17–19] Thus, the suc-
cessful determination of the structure of complex 6 provides
strong direct proof of the chemo- and regioselectivity of this
zirconocene-mediated multicomponent synthesis of 5-azain-
doles. The hydrolysis of 6 with water afforded the corre-
sponding pyrroloACHTUNGTRENNUNG[3,2-c]pyridine derivative 4b in a quantita-
tive yield. The hydrolysis of the reaction intermediate 6
leading to 5-azaindoles 1 was referred to in our previous
communication.[9a]
3,7-Diphenyl-2,4,6-tri-o-tolyl-1H-pyrroloACTHNUGRTENUNG[3,2-c]pyridine (1c): White solid,
isolated yield: 62% (333 mg). M.p. 2188C. 1H NMR (300 MHz, CDCl3,
258C, TMS): d=1.99 (s, 3H), 2.14 (s, 3H), 2.21 (s, 3H), 6.44–7.51 (m,
22H), 8.40 ppm (s, 1H); 13C NMR (75 MHz, CDCl3, 258C, TMS): d=
20.13, 20.32, 117.37, 118.37, 121.09, 124.77, 124.99, 125.26, 125.64, 126.78,
127.17, 127.44, 128.71, 129.37,129.81,129.97, 130.39, 131.00, 131.07, 131.69,
133.61, 135.57, 135.95, 136.02, 136.08, 136.56, 137.55, 139.66, 140.36,
148.89, 152.39 ppm; HRMS: m/z: calcd for C40H32N2: 540.2566; found:
540.2552; elemental analysis calcd (%) for C40H32N2: C 88.85, H 5.96, N
5.18; found: C 88.61, H 6.06, N 5.00.
Conclusions
We have developed a zirconocene-mediated one-pot multi-
component synthesis of pyrroloACTHNUTRGNEUGN[3,2-c]pyridine derivatives
(5-azaindoles) from one molecule of a silicon-tethered diyne
and three molecules of different or identical organonitriles.
This multicomponent one-pot process led to the incorpora-
tion of the four molecules into the final 5-azaindole prod-
ucts chemo- and regioselectively and represents a syntheti-
cally useful method for the preparation of otherwise un-
3,7-Bis(4-bromophenyl)-2,4,6-triphenyl-1H-pyrroloACHTNUTRGNEUNG[3,2-c]pyridine (1d):
White solid, isolated yield: 60% (393 mg). 1H NMR (300 MHz, CDCl3,
258C, TMS): d=6.74 (d, J=7.8 Hz, 2H), 7.04–7.55 (m, 21H), 8.36 ppm
(s, 1H); 13C NMR (75 MHz, CDCl3, 258C, TMS): d=114.73, 116.37,
120.29, 121.27, 121.95, 127.13, 127.45, 127.80, 128.33, 128.49, 128.77,
129.53, 130.46, 130.71, 131.45, 131.80, 132.33, 132.49, 133.43, 134.96,
136.22, 139.23, 140.16, 148.69, 153.04 ppm; HRMS: m/z: calcd for
C37H24N2Br2: 656.0286; found: 656.0281.
available but very important pyrroloACTHNUTRGNEUNG[3,2-c]pyridine deriva-
tives. A wide variety of organonitriles, either aliphatic or ar-
omatic with both electron-withdrawing and -donating
groups, could be used in this reaction to afford 5-azaindoles
in good-to-excellent isolated yields. Furthermore, we have
successfully isolated a key intermediate containing the
Me2Si and Cp2Zr moieties in high yield, the structure of
which was characterised by X-ray single-crystal structural
analysis. The isolation and structural determination of the
key intermediate, which incorporates five molecules, has al-
lowed a deeper understanding of the reaction mechanism of
this one-pot multicomponent process.
3,7-Bis(4-bromophenyl)-2,4,6-tris(4-methoxyphenyl)-1H-pyrroloACHTUNGTRENNUNG[3,2-
c]pyridine (1e): White solid, isolated yield: 48% (358 mg). 1H NMR
(300 MHz, CDCl3, 258C, TMS): d=6.56 (d, J=7.8 Hz, 2H), 6.73–6.82
(m, 6H), 7.11–7.25 (m, 6H), 7.28 (d, J=8.4 Hz, 2H), 7.37 (d, J=8.1 Hz,
2H), 7.55 (d, J=7.5 Hz, 2H), 8.29 ppm (s, 1H); 13C NMR (75 MHz,
CDCl3, 258C, TMS): d=115.38, 117.11, 121.50, 122.24, 122.92, 124.85,
124.90, 124.95, 125.00, 126.46, 126.51, 126.56, 126.60, 127.61, 127.84,
128.97, 129.28, 130.37, 130.55, 130.61, 130.77, 130.91, 131.13, 131.79,
132.85, 132.92, 133.37, 135.68, 137.39, 139.09, 140.64, 140.68, 141.69,
147.35, 151.84 ppm; HRMS: m/z: calcd for C40H30Br2N2O3: 746.0603;
found: 746.0597; elemental analysis calcd (%) for C40H30Br2N2O3: C
64.36, H 4.05, N 3.75; found: C 64.53, H 3.99, N 3.60.
3,7-Bis(4-methoxyphenyl)-2,4,6-tri-m-tolyl-1H-pyrroloACTHNUTRGNE[UNG 3,2-c]pyridine
(1 f): White solid, isolated yield: 45% (270 mg). 1H NMR (300 MHz,
CDCl3, 258C, TMS): d=2.05 (s, 3H), 2.26 (s, 3H), 2.28 (s, 3H), 6.53–7.44
(m, 20H), 8.35 ppm (s, 1H); 13C NMR (75 MHz, CDCl3, 258C, TMS): d=
21.05, 21.43, 21.51, 55.26, 55.30, 113.11, 114.62, 115.59, 117.14, 121.42,
125.79, 126.71, 127.09, 127.26, 127.56, 127.66, 127.86, 128.24, 128.41,
128.64, 128.79, 130.97, 131.28, 131.74, 132.10, 133.42, 135.76, 136.33,
137.16, 138.24, 139.29, 140.55, 141.07, 148.00, 152.69, 158.00, 159.01 ppm;
HRMS: m/z: calcd for C42H36N2O2: 600.2777; found: 600.2768.
Experimental Section
General methods: All the reactions were conducted under a slightly posi-
tive pressure of dry nitrogen using standard Schlenk line techniques or
under a nitrogen atmosphere in a Mikrouna SuperACTHNUTRGNE(NUG 1220/750) glovebox.
The nitrogen in the glovebox was constantly circulated through a copper/
molecular sieves catalytic unit. The oxygen and moisture concentrations
in the atmosphere of the glovebox were monitored by an O2/H2O
Combi-Analyzer to ensure both were always below 1 ppm. Unless other-
wise noted, all starting materials were commercially available and were
used without further purification. Toluene was heated at reflux and dis-
2,4,6-Tris(4-methoxyphenyl)-3,7-bis[4-(trifluoromethyl)phenyl]-1H-
pyrroloACTHUNRTGNEUNG[3,2-c]pyridine (1g): White solid, isolated yield: 32% (230 mg).
1H NMR (300 MHz, CDCl3, 258C, TMS): d=3.69 (s, 3H), 3.77 (s, 3H),
3.78 (s, 3H), 6.52 (d, J=8.4 Hz, 2H), 6.75 (d, J=8.7 Hz, 2H), 6.82 (d, J=
8.7 Hz, 2H), 7.00 (d, J=8.1 Hz, 2H), 7.15 (d, J=7.2 Hz, 4H), 7.26 (d, J=
8.4 Hz, 2H), 7.36 (d, J=8.7 Hz, 2H), 7.55 (d, J=8.4 Hz, 2H), 7.70 (d, J=
8.4 Hz, 2H), 8.30 ppm (s, 1H); 13C NMR (75 MHz, CDCl3, 258C, TMS):
d=55.10, 55.22, 55.32, 112.61, 113.34, 113.83, 114.34, 115.41, 120.98,
123.61, 124.37, 124.39, 124.44, 124.49, 126.20, 126.22, 126.30, 126.34,
129.91, 130.63, 130.71, 131.15, 131.72, 131.87, 132.61, 136.42, 138.86,
140.48, 148.02, 152.60, 158.99, 159.48, 159.80 ppm; HRMS: m/z: calcd for
C42H30F6N2O3: 724.2161; found: 724.2166; elemental analysis calcd (%)
for C42H30F6N2O3: C 69.61, H 4.17, N 3.87; found: C 69.31, H 4.36, N
3.67.
tilled from sodium/benzophone ketyl under
a nitrogen atmosphere.
nBuLi was obtained from Kanto Chemicals Co., Ltd. 1H and 13C NMR
spectra were recorded on a JNM-AL300 spectrometer (FT, 300 MHz for
1H; 75 MHz for 13C). Microelemental analyses were performed on a
MICRO CORDER JM10 apparatus.
Formation of pyrroloACHTUNGTRENNUNG[3,2-c]pyridine derivatives (5-azaindoles) 1a–o from
one molecule of a silicon-tethered diyne with three molecules of identical
organonitriles—Typical procedure for the preparation of 2,3,4,6,7-penta-
substituted-1H-pyrroloACHTUNGTRENNUNG[3,2-c]pyridine 1: nBuLi (2.1 mmol, 1.6m, 1.32 mL)
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Z. Xi et al.
2,4,6-Tris(3-bromophenyl)-3,7-bis[4-(trifluoromethyl)phenyl]-1H-pyrrolo-
[3,2-c]pyridine (1h): White solid, isolated yield: 42% (365 mg). 1H NMR
was purified by column chromatography (silica gel, hexane/ethyl acetate
(10:1) as eluent) to afford 1q as a white solid.
N
(300 MHz, CDCl3, 258C, TMS): d=6.91–7.77 (m, 20H), 8.46 ppm (s,
1H); 13C NMR (75 MHz, CDCl3, 258C, TMS): d=115.38, 117.11, 121.50,
122.24, 122.92, 124.95, 125.00, 126.46, 126.51, 126.56, 126.60, 127.61,
127.85, 128.97, 129.28, 130.37, 130.55, 130.61, 130.77, 130.90, 131.13,
131.79, 132.85, 132.92, 133.37, 135.68, 137.39, 139.09, 140.64, 140.68,
141.69, 147.35, 151.84 ppm; HRMS: m/z: calcd for C39H21N2F6Br2:
869.9139; found: 869.9146; elemental analysis calcd (%) for
C39H21N2F6Br2: C 53.76, H 2.43, N 3.22; found: C 53.60, H 2.68, N 3.00.
2,4,6-Tris(biphenyl-3-yl)-3,7-diphenyl-1H-pyrrolo
G
(1q):
White solid, isolated yield: 82% (300 mg); m.p. >3008C. 1H NMR
(300 MHz, CDCl3, 258C, TMS): d=6.95–7.66 (m, 37H), 8.51 ppm (s,
1H); 13C NMR (75 MHz, CDCl3, 258C, TMS): d=116.31, 117.79, 121.43,
125.74, 126.05, 126.30, 126.68, 126.80, 126.91, 126.94, 126.98, 127.12,
127.21, 127.47, 127.67, 127.80, 128.23, 128.27, 128.46, 128.51,128.69,
129.02, 129.43, 129.52, 129.62, 130.27, 130.83, 132.28, 134.48, 136.15,
136.25, 139.87, 140.02, 140.16, 140.29, 140.77, 141.06, 141.13, 141.34,
141.35, 147.88, 152.81 ppm; HRMS: m/z: calcd for C55H38N2: 726.3035;
found: 726.3022; elemental analysis calcd (%) for C55H38N2: C 90.88, H
5.27, N 3.85; found: C 90.72, H 5.30, N 5.08.
2,4,6-Tri(thiophen-2-yl)-3,7-di-p-tolyl-1H-pyrrolo
G
(1j):
Yellow solid, isolated yield: 50% (272 mg); m.p. 2568C. 1H NMR
(300 MHz, CDCl3, 258C, TMS): d=2.40 (s, 3H), 2.51 (s, 3H), 6.19–6.26
(m, 1H), 6.50–6.64 (m, 2H), 6.76–6.84 (m, 1H), 6.88–6.96 (m, 2H), 7.04–
7.32 (m, 7H), 7.32–7.50 (m, 4H), 8.13 ppm (s, 1H); 13C NMR (75 MHz,
CDCl3, 258C, TMS): d=21.37, 21.49, 115.40, 116.24, 119.95, 125.69,
125.78, 126.20, 126.39, 126.58, 126.62, 126.82, 127.09, 127.28, 128.70,
128.73, 128.83, 128.87, 128.94, 129.10, 129.15, 129.20, 129.50, 129.62,
129.82, 129.88, 130.00, 130.07, 130.56, 130.92, 131.31, 131.68, 132.11,
133.59, 137.25, 138.56, 141.34, 142.14, 143.39, 145.30, 145.65 ppm; HRMS:
m/z: calcd for C33H24N2S3: 544.1102; found: 544.1111.
2,4,6-Tris(biphenyl-4-yl)-3,7-diphenyl-1H-pyrrolo
(1p):
White solid, isolated yield: 53% (385 mg); m.p. >3008C. 1H NMR
(300 MHz, CDCl3, 258C, TMS): d=6.70–7.91 (m, 37H), 8.51 ppm (s,
1H); 13C NMR (75 MHz, CDCl3, 258C, TMS): d=116.23, 117.61, 121.70,
125.77, 125.81, 126.11, 126.37, 126.92, 127.00, 127.04, 127.09, 127.12,
127.22, 127.61, 127.77, 127.84, 128.64, 128.67, 128.74, 128.85, 129.38,
129.91, 130.22, 130.79, 130.92, 131.00, 134.66, 135.63, 136.13, 138.50,
139.50, 139.61, 139.92, 140.14, 140.65, 140.97, 141.11, 141.46, 147.61,
152.55 ppm; HRMS: m/z: calcd for C55H38N2: 726.3035; found: 726.3096.
2,4,6-Tricyclopropyl-3,7-diphenyl-1H-pyrroloACHTUNGETRN[UNNG 3,2-c]pyridine (1l): White
1
solid, isolated yield: 71% (277 mg); m.p. 150–1518C. H NMR (300 MHz,
CDCl3, 258C, TMS): d=0.51–0.53 (m, 2H), 0.59–0.74 (m, 4H), 0.74–0.85
(m, 2H), 0.97–1.08 (m, 2H), 1.08–1.20 (m, 2H), 1.62–2.07 (m, 3H), 6.89–
7.91 ppm (m, 11H); 13C NMR (75 MHz, CDCl3, 258C, TMS): d=7.10,
7.81, 9.07, 9.22, 13.58, 14.42, 115.42, 115.59, 120.78, 126.47, 127.39, 127.70,
129.02, 130.28, 131.33, 136.13, 136.36, 138.22, 148.63, 153.30 ppm; HRMS:
m/z: calcd for C28H26N2: 390.2096; found: 390.2088.
Formation of pyrrole derivatives 3a–d from one silicon-tethered diyne
and two identical organonitriles—general procedure for the preparation
of 1-(5-sec-butyl-2-benzyl-4-phenyl-1H-pyrrol-3-yl)-2-methylbutan-1-one
(3b): nBuLi (2.1 mmol, 1.6m, 1.32 mL) was added dropwise through a sy-
ringe to a toluene (10 mL) solution of [Cp2ZrCl2] (1.05 mmol, 307 mg) at
À788C (dry ice/acetone) in a 20 mL Schlenk tube. After the addition, the
reaction mixture was stirred at À788C for 1 h. Then bis(phenylethynyl)di-
methylsilane (2a; 1 mmol) was added and the reaction mixture was
warmed to 508C and stirred at this temperature for 3 h. Isobutyronitrile
(1.5 mmol, 0.135 mL) was then added and the reaction mixture was
stirred at this temperature for 1 h. The reaction mixture was quenched
with a saturated aqueous solution of NaHCO3 and the resulting mixture
was extracted with diethyl ether three times and then washed with water
and brine. The extract was dried over anhydrous MgSO4. The solvent was
evaporated in vacuo to give a yellow solid, which was subjected to SiO2
column chromatography using hexane/diethyl ether (1:1) as the eluent.
The characterisation data for compound 3a has been published in our
previous communication.[9a]
2,4,6-Tricyclohexyl-3,7-diphenyl-1H-pyrroloACHTUNGRETN[UNNG 3,2-c]pyridine (1m): White
1
solid, isolated yield: 59% (305 mg); m.p. 244–2458C. H NMR (300 MHz,
CDCl3, 258C, TMS): d=0.46–0.96 (m, 2H), 0.96–1.42 (m, 9H), 1.42–2.13
(m, 19H), 2.31–2.93 (m, 3H), 7.00–7.58 (m, 10H), 7.62 ppm (s, 1H);
13CNMR (75 MHz, CDCl3, 258C, TMS): d=25.74, 26.18, 26.29, 26.47,
26.60, 26.66, 32.23, 33.11, 33.21, 33.39, 35.60, 41.52, 41.71, 113.30, 115.28,
116.62, 126.80, 127.32, 127.78, 128.94, 129.96, 131.22, 136.68, 136.73,
138.48, 140.57, 153.12, 157.84 ppm; HRMS: m/z: calcd for C37H42N2:
516.3505; found: 516.3506.
2,4,6-Tris(4-bromophenyl)-3,7-diphenyl-1H-pyrroloACHTNUTRGNEUNG[3,2-c]pyridine (1n):
White solid, isolated yield: 61% (448 mg). 1H NMR (300 MHz, CDCl3,
258C, TMS): d=6.86–7.72 (m, 22H), 8.42 ppm (s, 1H); 13C NMR
(75 MHz, CDCl3, 258C, TMS): d=116.78, 118.34, 121.33, 121.56, 121.94,
122.62, 126.94, 127.33, 128.04, 128.10, 128.26, 128.63, 129.04, 129.51,
130.03, 130.07, 130.10, 130.44, 130.53, 130.96, 131.13, 132.74, 133.34,
133.56, 133.66, 134.83, 135.14, 140.96, 141.05, 142.34, 146.73, 151.42 ppm;
HRMS: m/z: calcd for C37H23Br3N2: 733.9391; found: 733.9388; elemental
analysis calcd (%) for C37H23Br3N2: C 60.44, H 3.15, N 3.81; found: C
88.61, H 6.06, N 5.00.
1-(5-sec-Butyl-2-benzyl-4-phenyl-1H-pyrrol-3-yl)-2-methylbutan-1-one
(3b): White solid, isolated yield: 50% (160 mg); m.p. 1258C. 1H NMR
(300 MHz, CDCl3, 258C, TMS): d=0.48–0.61 (m, 3H), 0.61–0.74 (m,
3H), 0.78–0.86 (m, 3H), 0.95–1.10 (m, 3H), 1.10–1.60 (m, 4H), 2.21–2.46
(m, 1H), 2.46–2.67 (m, 1H), 4.00–4.43 (s, 2H) 7.90 ppm (s,1H); 13C NMR
(75 MHz, CDCl3, 258C, TMS): d=11.64, 11.70, 11.97, 12.03, 15.87, 15.90,
16.29, 16.33, 20.89, 20.91, 26.39, 26.43, 26.75, 29.93, 29.99, 31.74, 33.84,
44.44, 44.51, 121.09, 121.19, 121.25, 126.58, 126.60, 127.98, 128.75, 128.97,
130.68, 132.64, 132.67, 132.69, 135.04, 135.06, 136.71, 136.75, 138.56,
204.54 ppm; HRMS: m/z: calcd for C26H31NO: 373.2406; found:
373.2408.
2,4,6-Tris(3-bromophenyl)-3,7-diphenyl-1H-pyrroloACHTNUTRGNEUNG[3,2-c]pyridine (1o):
White solid, isolated yield: 58% (404 mg). 1H NMR (300 MHz, CDCl3,
258C, TMS): d=6.86–7.48 (m, 22H), 8.38 ppm (s, 1H); 13C NMR
(75 MHz, CDCl3, 258C, TMS): d=116.35, 117.88, 121.53, 121.80, 122.47,
126.62, 128.01, 128.16, 129.04, 129.54, 129.89, 130.02, 130.09, 130.57,
130.78, 130.85, 131.02, 131.87, 132.05, 133.98, 135.14, 135.46, 138.11,
139.27, 141.07, 146.99, 151.73 ppm; HRMS: m/z: calcd for C37H23Br3N2:
733.9391; found: 733.9385; elemental analysis calcd (%) for C37H23Br3N2:
C 60.44, H 3.15, N 3.81; found: C 88.61, H 6.06, N 5.00.
1-(5-sec-Butyl-2-p-tolylmethyl-4-p-tolyl-1H-pyrrol-3-yl)-2-methylbutan-1-
one (3c): Yellow solid, isolated yield: 40% (187 mg); m.p. 118–1208C.
1H NMR (300 MHz, CDCl3, 258C, TMS): d=0.45–0.64 (m, 3H), 0.64–
0.75 (m, 3H), 0.75–0.92 (m, 3H), 0.92–1.09 (m, 3H), 1.09–1.21 (m, 1H),
1.22–1.42 (m, 2H), 1.42–1.66 (m, 1H), 2.18–2.36 (s, 3H), 2.36–2.45 (s,
3H), 2.45–2.66 (m, 2H), 3.96–4.61 (s, 2H), 6.63–7.50 (m, 8H), 8.09 ppm
(s, 1H); 13C NMR (75 MHz, CDCl3, 258C, TMS): d=11.66, 11.72, 12.00,
12.07, 15.96, 16.38, 20.94, 21.07, 21.23, 26.51, 26.78, 29.91, 29.97, 31.73,
33.51, 44.27, 44.33, 120.92, 121.00, 121.14, 128.67, 128.90, 129.44, 130.52,
132.55, 133.63, 133.66, 135.35, 135.40, 136.04, 136.08, 204.60 ppm; HRMS:
m/z: calcd for C28H35NO: 401.2719; found: 401.2718.
Formation of pyrroloACHTUNGTRENNUNG[3,2-c]pyridine derivatives (5-azaindoles) 1p and 1q
by Suzuki coupling of 1n and 1o and benzeneboronic acid—typical pro-
cedure for the preparation of 2,4,6-tri(biphenyl-3-yl)-3,7-diphenyl-1H-
pyrroloACHTUNGTRENNUNG[3,2-c]pyridine (1q): A solution of potassium carbonate (690 mg,
5.0 mmol) in water (2.5 mL) was added to a mixture of 1o (368 mg,
0.5 mmol) and benzeneboronic acid (244 mg, 2.0 mmol) in THF (5 mL).
After degassing the mixture and backfilling with nitrogen, [PdACTHUNRTGNEUNG(PPh3)4]
(29 mg, 0.025 mmol) was added and then the reaction mixture was
heated at reflux for 16 h. The mixture was extracted with dichlorome-
thane and washed with brine (3ꢂ100 mL). The organic extracts were
dried with anhydrous MgSO4. After removal of the solvent, the residue
[2-Benzyl-4-phenyl-5-(1-phenylcyclopropyl)-1H-pyrrol-3-yl](1-phenylcy-
clopropyl)methanimine (3d): Yellow solid, isolated yield: 53% (260 mg);
m.p. 166–1678C. H NMR (300 MHz, CDCl3, 258C, TMS): d=0.87 (t, J=
6.3 Hz, 2H), 0.95 (t, J=6.9 Hz, 2H), 1.85 (t, J=7.2 Hz, 2H), 1.31 (t, J=
7.2 Hz, 2H), 3.45 (s, 2H), 6.63–6.78 (m, 2H), 6.88–6.99 (m, 2H), 7.06–
7.32 (m, 16H), 7.42 (s, 1H), 7.65 ppm (s, 1H); 13C NMR (CDCl3, TMS):
1
12614
www.chemeurj.org
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2009, 15, 12608 – 12617

Multicomponent Synthesis of Azaindoles and Pyrroles
FULL PAPER
d=15.92, 19.81, 20.60, 32.22, 34.21, 121.34, 124.53, 124.56, 125.17, 125.83,
126.46, 126.64, 126.67, 127.47, 127.62, 127.66, 127.84, 127.88, 128.31,
128.41, 128.70, 128.74, 128.78, 129.51, 129.53, 130.65, 130.68, 135.65,
138.74, 142.20, 146.26, 182.22 ppm; HRMS: m/z: calcd for C36H32N2:
492.2566; found: 492.2548.
(300 MHz, CDCl3, 258C, TMS): d=0.74 (t, J=6.6 Hz, 3H), 0.87–1.35 (m,
12H), 1.35–1.78 (m, 8H), 3.09–3.24 (m, 2H), 3.30 (t, J=6.9 Hz, 2H),
2.78–3.13 (m, 2H), 6.66–7.89 (m, 10H), 9.30 ppm (s, 1H); 13CNMR
(CDCl3, TMS): d=13.98, 20.91, 22.22, 22.36, 26.20, 28.66, 29.29, 29.49,
31.16, 31.26, 115.52, 119.92, 128.33, 129.45, 129.63, 129.72, 129.82, 130.59,
131.50, 131.54, 133.69, 141.50, 146.23, 147.92, 156.04, 156.06 ppm; HRMS:
m/z: calcd for C31H38N2: 438.3035; found: 438.3029.
Formation of pyrroloACHTUNGTRENNUNG[3,2-c]pyridine derivatives 4a–f from one silicon-
tethered diyne, two molecules of the same organonitrile and a different
organonitrile—typical procedure for the preparation of 2,4-diisopropyl-
Isolation of reactive intermediate 6 from silicon-tethered diyne 2a, two
molecules of iPrCN and p-tolylCN: Compound 5 was isolated according
to our previous literature report.[9a] p-Tolunitrile (60 mL, 0.50 mmol) was
added through a syringe to a benzene solution of compound 5 (310 mg,
0.50 mmol) in a 20 mL Schlenk tube. After the reaction mixture was
stirred at 508C for 1 h, it was dried under vacuum and the residue was
washed with hexane. After filtering, the solid was dried under vacuum to
precipitate 6 as a brown powder (331 mg, 0.45 mmol, 90% yield). Single
crystals of 6 suitable for X-ray analysis were grown in tetrahydrofuran/
hexane at room temperature for 1 week. 1H NMR (300 MHz, C4D8O,
258C): d=0.11 (s, 3H; SiMe2), 0.17 (s, 3H; SiMe2), 0.52 (d, J = 6.6 Hz,
3H; CHMe2), 0.72 (d, J = 6.6 Hz, 3H; CHMe2), 0.85 (d, J = 6.9 Hz,
3,6,7-triphenyl-1H-pyrroloACHTNUTRGNE[NUG 3,2-c]pyridine (4a): nBuLi (2.1 mmol, 1.6m,
1.32 mL) was added dropwise through a syringe to a toluene (10 mL) so-
lution of [Cp2ZrCl2] (1.05 mmol, 307 mg) at À788C (dry ice/acetone) in a
20 mL Schlenk tube. After the addition, the reaction mixture was stirred
at À788C for 1 h. Then bis(phenylethynyl)dimethylsilane (2a; 1 mmol)
was added and the reaction mixture was warmed to 508C and stirred at
this temperature for 3 h. Isobutyronitrile (1.5 mmol, 0.135 mL) was then
added and the reaction mixture was stirred at this temperature for 1 h.
Then benzonitrile (1.2 mmol, 124 mg) was added and the reaction mix-
ture was stirred at 508C for 1 h. The reaction mixture was quenched with
a saturated aqueous solution of NaHCO3. The resulting mixture was ex-
tracted with diethyl ether three times and then washed with water and
brine. The extract was dried over anhydrous MgSO4. The solvent was
evaporated in vacuo to give a yellow solid, which was subjected to Al2O3
column chromatography using hexane/diethyl ether (5:1) as the eluent.
3H; CHMe2), 1.39 (d, J
= 6.9 Hz, 3H; CHMe2), 2.12–2.29 (m, 2H;
CHMe2), 2.34 (s, 3H; CH3), 6.23 (s, 5H; C5H5), 6.45 (s, 5H; C5H5), 7.03
(s, 4H; C6H5), 7.13–7.37 (m, 9H; C6H5), 7.55 ppm (d, J = 8.1 Hz, 2H;
C6H5); 13C NMR (75.4 MHz, C4D8O, 25 8C): d À5.0, 0.3, 18.5, 20.3, 21.0,
25.5, 26.2, 34.7, 35.6, 57.2, 111.3, 111.7, 119.6, 125.6, 125.8, 126.9, 127.0,
127.7, 127.9, 128.6, 128.7, 131.0, 132.1, 137.9, 138.6, 141.3, 142.7, 144.2,
145.0, 175.7, 185.7 ppm; elemental analysis calcd (%) for C48H55N3OSiZr:
C 71.24, H 6.85, N 5.19; found: C 70.84, H 6.90, N 5.00.
2,4-Diisopropyl-3,6,7-triphenyl-1H-pyrroloACTHNUTRGNE[UNG 3,2-c]pyridine (4a): Single
crystals of 4a suitable for X-ray analysis were grown in hexane at room
temperature for 3 days. White solid, isolated yield: 61% (262 mg); m.p.
210–2118C. 1H NMR (300 MHz, CDCl3, 258C, TMS): d=1.16–1.19 (m,
12H), 2.93–3.07 (m, 2H), 7.15–7.42 (m, 15H), 7.96 ppm (s, 1H);
13C NMR (75 MHz, CDCl3, 258C, TMS): d=22.06, 22.66, 25.66, 31.29,
113.50, 116.34, 120.81, 126.50, 127.09, 127.30, 127.38, 127.98, 129.10,
130.18, 130.54, 131.11, 136.33, 136.89, 139.00, 141.24, 142.47, 146.67,
159.06 ppm; HRMS: m/z: calcd for C31H30N2: 430.2436; found: 430.2434.
X-ray crystallographic studies: Single crystals of 4a, 4c and 6 suitable for
X-ray analysis were grown as described above. The crystals of 6 were ma-
nipulated under a nitrogen atmosphere and sealed in a thin-walled glass
capillary. Data were collected for 4a and 4c at 208C on a Rigaku RAXIS
RAPID IP diffractometer using graphite-monochromated MoKa radiation
(l=0.71073 ꢁ). Data was collected for 6 at À1508C on a Rigaku RAXIS
RAPID IP diffractometer, using graphite-monochromated MoKa radia-
tion (l=0.71073 ꢁ). The crystal class and unit cell parameters were deter-
mined by the Rapid-AUTO (Rigaku 2000) program package. The raw
frame data were processed by using Crystal Structure (Rigaku/MSC
2000) to yield the reflection data file. The structures of 4a, 4c and 6 were
solved by using the SHELXTL program.[20] Refinement was performed
anisotropically on F2 for all non-hydrogen atoms by the full-matrix least-
squares method. The hydrogen atoms were placed at calculated positions
and were included in the structure calculation without further refinement
of the parameters. The crystal data, data collection and processing pa-
rameters for compounds 4a, 4c and 6 are summarised in the Supporting
Information.
2,4-Diisopropyl-3,7-diphenyl-6-p-tolyl-1H-pyrrolo
G
(4b):
The characterisation data for compound 4b has been published in our
previous communication.[9b]
2,4-Diisopropyl-3,7-diphenyl-6-(thiophen-2-yl)-1H-PyrroloACTHNUTRGENUGN[3,2-c]pyridine
(4c): Single crystals of 4c suitable for X-ray analysis were grown in
hexane/diethyl ether at room temperature for 2 days. White solid, isolat-
ed yield: 68% (296 mg); m.p. 208–2098C. 1H NMR (300 MHz, CDCl3,
258C, TMS): d=1.43 (d, J=7.2 Hz, 6H), 1.18 (d, J=6.9 Hz, 6H), 2.85–
3.10 (m, 2H), 2.40 (s, 3H), 2.45–2.62 (m, 1H), 2.72–2.30 (m, 1H), 6.30–
6.39 m, 1H), 6.72–6.79 (m, 1H), 7.11–7.18 (m, 1H), 7.22–7.62 (m, 10H),
7.69 (s, 1H); 13C NMR (75 MHz, CDCl3, 258C, TMS): d=22.10, 22.60,
25.64, 31.31, 113.71, 114.62, 120.40, 124.99, 125.92, 127.09, 127.15, 127.97,
128.25, 129.67, 130.09, 131.04, 136.10, 136.18, 139.52, 140.08, 142.64,
147.34, 158.75 ppm; HRMS: m/z: calcd for C29H28N2S: 436.1973; found:
436.1977.
CCDC-231130 (4a), -280150 (4c) and -730834 (6) contain the supplemen-
tary crystallographic data for this paper. These data can be obtained free
of charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data request/cif.
2,4-Diisopropyl-6-(4-methoxyphenyl)-3,7-diphenyl-1H-pyrroloACTHNUGTRNEUNG[3,2-c]pyri-
dine (4d): White solid, isolated yield: 47% (216 mg); m.p. 181–1828C.
1H NMR (300 MHz, CDCl3, 258C, TMS): d=1.16 (d, J=7.2 Hz, 6H),
1.19 (d, J=6.6 Hz, 6H), 2.85–3.10 (m, 2H), 2.40 (s, 3H), 2.45–2.62 (m,
1H), 2.77–3.28 (m, 2H), 3.73 (s, 3H), 6.60–6.90 (m, 2H), 6.96–7.56 (m,
12H), 7.96 (s, 1H); 13C NMR (75 MHz, CDCl3, 258C, TMS): d=22.07,
22.63, 25.61, 31.25, 55.09, 112.89, 113.41, 115.80, 120.51, 127.04, 127.23,
127.94, 129.15, 130.12, 131.07, 131.60, 133.83, 136.35, 137.04, 139.09,
142.24, 146.26, 158.38, 158.86 ppm; HRMS: m/z: calcd for C32H32N2O:
460.2515; found: 460.2509.
Acknowledgements
This work was supported by the National Natural Science Foundation of
China. Cheung Kong Scholars Program, Dow Corning Corporation, Qiu
Shi Science & Technologies Foundation,and BASF are gratefully ac-
knowledged.
2,4-Diisopropyl-3,7-diphenyl-6-propyl-1H-pyrrolo
G
(4e):
Yellow solid, isolated yield: 60% (238 mg); m.p. 162–1638C. 1H NMR
(300 MHz, CDCl3, 258C, TMS): d=0.84 (d, J=7.2 Hz, 3H), 1.14 (d, J=
6.6 Hz, 6H), 1.70 (d, J=7.5 Hz, 6H), 1.57–1.93 (m, 2H), 2.67 (t, J=
7.5 Hz, 2H), 2.78–3.13 (m, 2H), 6.92–7.62 (m, 10H), 7.73 ppm (s, 1H);
13C NMR (75 MHz, CDCl3, 258C, TMS): d=14.07, 21.97, 22.66, 23.54,
25.52, 30.95, 36.45, 113.17, 116.61, 119.68, 126.91, 127.44, 127.86, 128.97,
129.95, 131.06, 136.58, 136.67, 138.86, 141.44, 149.30, 141.44 ppm; HRMS:
m/z: calcd for C28H32N2: 396.2566; found: 396.2554.
[1] For recent reviews on azaindoles, see: a) J. J. Song, J. T. Reeves, F.
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6-Hexyl-2,4-diisopropyl-3,7-diphenyl-1H-pyrrolo
[3,2-c]pyridine
(4 f):
White solid, isolated yield: 55% (241 mg); m.p. 187–1888C. 1H NMR
Chem. Eur. J. 2009, 15, 12608 – 12617
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Multicomponent Synthesis of Azaindoles and Pyrroles
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Received: September 1, 2009
Published online: October 30, 2009
Chem. Eur. J. 2009, 15, 12608 – 12617
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
12617