Palladium-catalyzed C2-acylation of indoles with aryl and alkyl aldehydes

Article abstract of DOI:10.1016/j.tet.2014.08.025

A palladium-catalyzed C2-acylation of indoles with aryl and alkyl aldehydes via C-H functionalization is reported. The method shows excellent functional group tolerance and provides a straightforward way for the preparation of 2-aroylindoles.

Full text of DOI:10.1016/j.tet.2014.08.025

Tetrahedron 70 (2014) 7490e7495
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Palladium-catalyzed C2-acylation of indoles with aryl and alkyl
aldehydes
Xiao-Biao Yan a, Yong-Wen Shen b, Dao-Qian Chen a, Pin Gao a, Ying-Xiu Li a,
,
a
Xian-Rong Song a, Xue-Yuan Liu a , Yong-Min Liang
*
a State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, PR China
b College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 24 April 2014
Received in revised form 29 July 2014
Accepted 8 August 2014
Available online 15 August 2014
A palladium-catalyzed C2-acylation of indoles with aryl and alkyl aldehydes via CeH functionalization is
reported. The method shows excellent functional group tolerance and provides a straightforward way for
the preparation of 2-aroylindoles.
Ó 2014 Elsevier Ltd. All rights reserved.
Keywords:
Palladium
Acylation
Indole
Aldehyde
2-Aroylindole
1. Introduction
formation of intractable isomeric mixtures. In particular, the 2-
aroylindole moiety attracts much attention as it is prevalent in
Transition-metal-catalyzed CeH bond functionalization directed
by heteroatom directing groups is one of the most powerful tools in
recent organic synthesis for the regioselective formation of car-
bonecarbon and carboneheteroatom bonds.1 In particular, the
palladium-catalyzed directed acylation of the arene CeH bonds has
attracted great interest. In 2009, Cheng2 first reported a palladium-
catalyzed oxidative coupling of 2-arylpyridines with aromatic
aldehydes toaffordaromatic ketones. Later, palladium-catalyzed the
directed acylations of 2-arylpyridines,3 anilides,4 oxime,5 azoar-
enes,6 and benzylamines7 with aldehydes, alcohols or aryl methanes
were described. Furthermore, palladium-catalyzed decarboxylative
drug fragments.11 In 2012, Li12 reported a rhodium-catalyzed
oxidative C2-acylation of indoles with aryl and alkyl aldehydes
via CeH bond activation. Zhu and co-workers13 disclosed a palla-
dium-catalyzed decarboxylative C2-acylation of indoles with
a-oxocarboxylic acids leading to 2-aroylindole. However, these
approaches need stoichiometric silver salt as an oxidant. In addi-
tion, for alkyl aldehydes, the former shows lower activity and needs
longer reaction time, the latter does not give alkyl acylation
product. Therefore, novel and efficient methods to synthesis C2-
acylation of indoles is still desired. Herein, we describe a palla-
dium-catalyzed C2-acylation of indoles with aldehydes using
a more desirable reagent, TBHP (tert-butyl hydroperoxide), as the
oxidant. This reaction proceeds smoothly with aromatic and
aliphatic aldehydes, and shows broad substrate generality. The 2-
pyridinyl director is readily removable on the indole nitrogen atom.
acylations of the arene CeH bond using
a-oxocarboxylic acids as acyl
sources were reported.8 The carbo-acylation of 2-arylpyridines with
a
-diketones via Pd-catalyzed CeH bond activation and CeC bond
cleavage were also reported.9
Meanwhile, owing to their ubiquity in biologically active com-
pounds, pharmaceuticals, and natural products, the efficient con-
struction of functionalized indolyl analogues is a long-standing
focus for synthetic chemists.10 However, challenging still remain,
because regioselectivities must be well controlled by avoiding the
2. Results and discussion
Initial studies began with the direct CeH acylation of 1-(pyr-
idin-2-yl)-1H-indole (1a) with three equivalents of benzaldehyde
(2a) in the presence of 10 mol % Pd(OAc)2 and stoichiometric
TBHP (2.0 equiv) in toluene at 80 ꢀC for 10 h. As expected, the
desired product 3a was obtained in 51% yield (Table 1, entry 1).
Increasing the amount of TBHP resulted in lower yield (Table 1,
* Corresponding author. Tel.: þ86 931 891 2593; fax: þ86 931 891 2582; e-mail
address: liuxuey@lzu.edu.cn (X.-Y. Liu).
http://dx.doi.org/10.1016/j.tet.2014.08.025
0040-4020/Ó 2014 Elsevier Ltd. All rights reserved.

X.-B. Yan et al. / Tetrahedron 70 (2014) 7490e7495
7491
Table 1
Table 2
Optimization of the reaction conditionsa
Scope of various aldehydesa
Entry
2a (equiv)
Oxidant
Additive
Solvent
Yield (%)b
1
3.0
3.0
3.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
TBHP
TBHP
TBHP
TBHP
DTBP
K2S2O8
Ag2O
PhI(OAc)2
DCP
Benzoquinone
TBHP
d
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
DCE
EtOAc
MeCN
Toluene
Toluene
Toluene
51
47
34
67
2c
3d
4
d
d
d
5
6
7
8
d
n.r.e
n.r.
n.r.
Trace
n.r.
n.r.
Trace
50
d
d
d
9
d
10
11
12
13
14
15g
16
d
d
TBHP
TBHP
TBHP
TBHP
d
d
45
PivOH
PivOH
AcOH
79f
70
TBHP
39
a
Reaction condition: 1a (0.2 mmol), 2a, Pd(OAc)2 (10 mol %), TBHP (2.0 equiv, 70%
aqueous solution), additive (2.0 equiv), toluene (2.0 mL), 80 ꢀC, 10 h, under argon.
b
Isolated yield.
TBHP (3.0 equiv).
TBHP (5.0 equiv).
c
d
e
n.r.¼no reaction.
f
The optimal condition.
g
PivOH (1.2 equiv).
entries 2 and 3). When 5 equiv of benzaldehyde were employed
the reaction yield increased to 67% (Table 1, entry 4). Other oxi-
dants, such as DTBP (di-tert-butyl peroxide), K2S2O8, Ag2O,
PhI(OAc)2, DCP (dicumyl peroxide), and benzoquinone, were in-
effective for this reaction (Table 1, entries 5e10). Solvent
screening showed that toluene was optimal solvent, whereas
other solvents such as DCE, EtOAc, and MeCN failed to yield better
results (Table 1, entries 11e13). After further optimization, the use
of 2 equiv of PivOH (pivalic acid) as an additive resulted in the
acylation reaction to afford the highest yield in 79% (Table 1, entry
14), because it can inhibit the side reactions and improve the yield
of 3a.14 However, either decreasing the amount of PivOH or
adding other acid additive (AcOH) was relatively ineffective
(Table 1, entries 15 and 16).
a
Reaction condition: 1a (0.2 mmol), 2 (5.0 equiv.), Pd(OAc)2 (10 mol%),
TBHP (2.0 equiv., 70% aqueous solution), PivOH (2.0 equiv.), toluene (2.0
mL), 80 oC, 10 h, under argon.
To explore the substrate scope of this protocol, the optimized
reaction conditions were applied to a series of aldehydes. As shown
in Table 2, the CeH acylation of 1a with various aryl aldehydes
possessing electron-withdrawing or -donating substituents could
proceed smoothly and furnished the corresponding products.
Moreover, substrate with the strong electron-donating methoxy
group at the para position of the phenyl ring delivered a lower yield
than its counterparts substituted by the methyl group (3b vs 3e).
Meanwhile, the ortho-substituted benzaldehydes gave lower yields
of acylated products possibly due to their higher steric hindrance
(3jel). 1-Naphthylaldehyde and 2-naphthylaldehyde also un-
derwent the acylation reaction to afford product 3p and 3o in good
yield. In addition, the heterocyclic aldehydes 2q and 2r also par-
ticipated in the oxidative coupling to furnish 3q and 3r in good
yields (64% and 74%). To our delight, this reaction is not limited to
aryl aldehydes. Under the standard reaction conditions, aliphatic
aldehydes such as n-heptanal (2s) and cyclohexanal (2t) could also
undergo this coupling reaction smoothly to provide product 3s and
3t in 79% and 68% yield, respectively. It is worth noting that re-
actions with conjugated aldehydes underwent the reaction fluently
and gave our desired products 3u and 3v in 64% and 40% yield,
respectively.
We next further investigated the scope of indoles. The results
from Table 3 demonstrated that the substitution on the indoles
showed no significant electronic effects. All the reactions pro-
ceeded smoothly in moderate to good yields and tolerated various
functional groups such as methoxy, chloro, bromo, and ester
groups. Yet, 3-substituted indoles gave an inferior yield due to
steric hindrance (4e and 4f). Acylation of indole derivatives is also
possible by using a pyrimidine directing group. The corresponding
2-aroylindole was obtained in slightly higher yield (compare 3a
with 4g). Furthermore, the reaction of 1-(pyridin-2-yl)-1H-pyrrole
(1i) with benzaldehyde was also investigated and selective diac-
ylation product 4h was isolated in 77% yield.
To investigate the reactivities of aromatic and aliphatic alde-
hydes, a completing acylation reaction was carried out (Scheme 1).
Exposure of 1a to equimolar quantities of aromatic aldehyde 2a and
aliphatic aldehyde 2s under the standard conditions provided 3a
and 3s in 39% and 58% yield, respectively. The results indicate that
aliphatic aldehydes are more reactive than aromatic aldehydes for
the transformation under relatively low temperature.7

7492
X.-B. Yan et al. / Tetrahedron 70 (2014) 7490e7495
On the basis of the previous reports,3e7 a plausible catalytic cycle
Table 3
Scope of indolesa
of this transformation is proposed (Scheme 3). Firstly, a five mem-
bered cyclopalladated intermediate A was generated through CeH
activation of indole. Then the reaction of aldehyde with TBHP gen-
erated a reactive acyl radical, which next reacted with intermediate
A to realize the oxidation of Pd(II) to dimeric Pd(III)16 or Pd(IV)17
species B. Finally, the species B underwent reductive elimination
to afford the acylated product and released the Pd(II) species for the
next run. Consistent with the involvement of radical intermediates,
no acylated product was observed in the presence of a radical in-
hibitor (2.0 equiv), TEMPO (2,2,6,6-tetramethylpiperidinooxy).
Scheme 3. Plausible reaction mechanism.
a
Reaction condition: 1 (0.2 mmol), 2a (5.0 equiv.), Pd(OAc)2 (10 mol%),
TBHP (2.0 equiv., 70% aqueous solution), PivOH (2.0 equiv.), toluene (2.0
3. Conclusions
b
mL), 80 oC, 10 h, under argon. 2a (10.0 equiv.), TBHP (4.0 equiv., 70%
aqueous solution) were used.
In summary, we have developed an efficient protocol for the Pd-
catalyzed C2-acylation of indoles with aldehydes using TBHP as an
oxidant and PivOH as an additive. The method allows for using
aromatic, aliphatic, and conjugated aldehydes as acyl sources,
shows excellent functional group tolerance, and provides a conve-
nient access toward various types of 2-aroylindoles.
4. Experimental section
4.1. General
Scheme 1. Completing acylation of 1-(pyridin-2-yl)-1H-indole between aromatic and
aliphatic aldehydes.
All reactions were carried out under an atmosphere of argon
unless otherwise noted. Column chromatography was carried out
on silica gel. 1H NMR and 13C NMR spectra were measured on
400 MHz spectrometer, using CDCl3 as the solvent with tetrame-
The 2-aroylindole is a common structural motif in many natural
products and pharmaceutical compounds. If we can further remove
the directing group (2-pyridinyl director) of acylated products, it
would complete the synthetic approach to modified 2-aroylindoles.
Then we attempted to remove the directing group from the acyl-
ated products in order to increase the reaction practicability.
Compounds 3a then underwent depyridination by treatment of
MeOTf (methyl trifluoromethanesulfonate) in dichloromethane
and sodium hydroxide in methanol.15 Eventually, 3a0 was produced
in 67% yield (Scheme 2).
thylsilane (TMS) as the internal standard. Chemical shifts (d) are
given in parts per million relative to TMS, the coupling constants J
are given in Hertz. All products were further characterized by high
resolution mass spectra. Copies of their 1H NMR and 13C NMR
spectra are provided. All melting points were determined on a mi-
croscopic apparatus and were uncorrected.
4.2. General procedure for the acylation of indoles
A 10 mL of reaction tube was charged with indole (1, 0.20 mmol),
aldehyde (2, 1.00 mmol), Pd(OAc)2 (4.5 mg, 0.02 mmol), TBHP
(55
mL, 0.40 mmol, 70% aqueous solution), PivOH (40.8 mg,
0.4 mmol), and toluene (2.0 mL) under argon atmosphere. The re-
action vessel was placed in an oil bath. After the reaction was carried
out at 80 ꢀC for 10 h, it was cooled to room temperature, extracted
with EtOAc (3ꢁ10 mL). The organic layers were combined, dried
over Na2SO4, and concentrated to yield the crude product, which
Scheme 2. Removal of 2-pyridinyl director.

X.-B. Yan et al. / Tetrahedron 70 (2014) 7490e7495
7493
was further purified by flash chromatography, affording the desired
product 3.
126.4, 122.9, 122.1, 121.9, 121.0, 115.7, 111.5, 21.6. HRMS (ESI) m/z:
calculated for C21H17N2O [MþH]þ: 313.1335, found: 313.1341.
4.3. General procedure for the removal of 2-pyridinyl director
4.4.6. (1-(Pyridin-2-yl)-1H-indol-2-yl)(4-(trifluoromethyl)phenyl)
methanone (3f). (58.9 mg, 80%), semi-solid. 1H NMR (400 MHz,
Methyl trifluoromethanesulfonate (27
m
L, 0.24 mmol) was
CDCl3):
d
8.56e8.57 (m, 1H), 8.09 (d, J¼8.0 Hz, 2H), 7.87e7.91 (m,
added dropwise to a solution of 3a (59.6 mg, 0.20 mmol) in dry
CH2Cl2 (5.0 mL) at 0 ꢀC, and the resulting solution was stirred for
12 h at room temperature. Then the solvent was removed under
vacuum, and the residue was dissolved in MeOH (3.0 mL). A 2 M
aq NaOH solution (1.2 mL) was added, and stirring was continued at
60 ꢀC for 12 h. The solvents were removed, and the resulting resi-
due was extracted with EtOAc (2ꢁ15 mL). The combined organic
layers were washed with brine, dried over Na2SO4, and concen-
trated in vacuo. The residue was purified by flash chromatography,
affording the desired product 3a0 (29.4 mg, 67%) as a white solid.
1H), 7.73e7.77 (m, 3H), 7.45e7.51 (m, 2H), 7.38e7.41 (m, 1H),
7.31e7.35 (m, 1H), 7.23e7.27 (m, 1H), 7.20 (s, 1H). 13C NMR
(100 MHz, CDCl3):
d 185.6, 151.2, 149.4, 141.1, 139.9, 138.2, 135.4,
133.8 (q, J¼32.0 Hz), 130.0, 127.1, 126.7, 125.3, 125.3, 123.7 (q,
J¼271.0 Hz), 123.2, 122.5, 122.2, 121.0, 116.8, 111.5. HRMS (ESI) m/z:
calculated for C21H14F3N2O [MþH]þ: 367.1053, found: 367.1049.
4.4.7. 4-(1-(Pyridin-2-yl)-1H-indole-2-carbonyl)benzonitrile
(3g). (46.7 mg, 72%), white solid. Mp 50e52 ꢀC. 1H NMR (400 MHz,
CDCl3):
d 8.55e8.57 (m, 1H), 8.05e8.07 (m, 2H), 7.89e7.93 (m, 1H),
7.74e7.80 (m, 3H), 7.46e7.51 (m, 2H), 7.39e7.43 (m, 1H), 7.33e7.36
4.4. Characterization data of products
(m, 1H), 7.24e7.28 (m, 1H), 7.19 (s, 1H). 13C NMR (100 MHz, CDCl3):
d
185.1,151.1, 149.5,141.7, 140.0, 138.3,135.1, 132.1, 130.1,127.3, 126.7,
4.4.1. Phenyl(1-(pyridin-2-yl)-1H-indol-2-yl)methanone
123.3, 122.6, 122.3, 120.9, 118.1, 116.8, 115.8, 111.5. HRMS (ESI) m/z:
(3a). (47.0 mg, 79%), white solid. Mp 31e33 ꢀC. 1H NMR (400 MHz,
calculated for C21H14N3O [MþH]þ: 324.1131, found: 324.1130.
CDCl3):
d
8.56e8.58 (m, 1H), 8.00 (d, J¼7.2 Hz, 2H), 7.84e7.88
(m, 1H), 7.73 (d, J¼8.0 Hz, 1H), 7.58e7.62 (m, 1H), 7.47e7.54 (m, 3H),
7.43 (d, J¼8.0 Hz, 1H), 7.35e7.39 (m, 1H), 7.29e7.32 (m, 1H),
7.24e7.25 (m, 1H), 7.20e7.22 (m, 1H). 13C NMR (100 MHz, CDCl3):
4.4.8. (3-Chlorophenyl)(1-(pyridin-2-yl)-1H-indol-2-yl)methanone
(3h). (53.5 mg, 80%), white solid. Mp 31e33 ꢀC. 1H NMR (400 MHz,
CDCl3):
d 8.57e8.58 (m, 1H), 7.97e7.98 (m, 1H), 7.87e7.91 (m, 2H),
d
186.9, 151.5, 149.3, 139.7, 138.2, 138.0, 136.0, 132.6, 129.9, 128.3,
7.75 (d, J¼8.0 Hz, 1H), 7.55e7.57 (m, 1H), 7.50e7.52 (m, 1H),
126.8, 126.6, 123.0, 122.2, 122.0, 121.1, 116.2, 111.5. HRMS (ESI) m/z:
7.42e7.46 (m, 2H), 7.36e7.40 (m, 1H), 7.31e7.34 (m, 1H), 7.25e7.27
calculated for C20H15N2O [MþH]þ: 299.1179, found: 299.1184.
(m, 1H), 7.21e7.23 (m, 1H). 13C NMR (100 MHz, CDCl3):
d 185.3,
151.2, 149.3, 139.7, 139.7, 138.2, 135.4, 134.5, 132.5, 129.8, 129.6,
127.9, 126.9, 126.7, 123.1, 122.4, 122.1, 121.0, 116.5, 111.4. HRMS (ESI)
4.4.2. (4-Methoxyphenyl)(1-(pyridin-2-yl)-1H-indol-2-yl)meth-
anone (3b). (44.0 mg, 67%), white solid. Mp 92e94 ꢀC. 1H NMR
m/z: calculated for
333.0792.
C
20H14ClN2O [MþH]þ: 333.0789, found:
(400 MHz, CDCl3):
d
8.55e8.56 (m, 1H), 8.01e8.03 (m, 2H),
7.82e7.86 (m, 1H), 7.72 (d, J¼8.0 Hz, 1H), 7.55 (d, J¼8.4 Hz, 1H),
7.33e7.41 (m, 2H), 7.21e7.29 (m, 2H), 7.16 (s, 1H), 6.96e6.98
4.4.9. (1-(Pyridin-2-yl)-1H-indol-2-yl)(m-tolyl)methanone
(m, 2H), 3.87 (s, 3H). 13C NMR (100 MHz, CDCl3):
d
185.7, 163.4,
(3i). (55.1 mg, 88%), semi-solid. 1H NMR (400 MHz, CDCl3):
151.4, 149.2, 139.3, 138.0, 136.2, 132.2, 130.8, 126.9, 126.2, 122.8,
122.1, 121.8, 120.9, 115.1, 113.6, 111.4, 55.5. HRMS (ESI) m/z: calcu-
lated for C21H17N2O2 [MþH]þ: 329.1285, found: 329.1281.
d
8.57e8.59 (m, 1H), 7.81e7.88 (m, 3H), 7.74 (d, J¼8.0 Hz, 1H), 7.53
(d, J¼8.4 Hz, 1H), 7.35e7.43 (m, 4H), 7.28e7.31 (m, 1H), 7.23e7.25
(m, 1H), 7.20e7.21 (m, 1H), 2.42 (s, 3H). 13C NMR (100 MHz, CDCl3):
d
187.0, 151.4, 149.2, 139.6, 138.1, 136.1, 134.1, 133.4, 130.5, 130.4,
4.4.3. (4-Bromophenyl)(1-(pyridin-2-yl)-1H-indol-2-yl)methanone
128.1, 127.2, 126.8, 126.5, 123.0, 122.2, 121.9, 121.0, 116.0, 111.5, 21.3.
HRMS (ESI) m/z: calculated for C21H17N2O [MþH]þ: 313.1335,
found: 313.1338.
(3c). (71.9 mg, 95%), white solid. Mp 37e39 ꢀC. 1H NMR (400 MHz,
CDCl3):
d
8.56e8.57 (m, 1H), 7.85e7.90 (m, 3H), 7.73 (d, J¼8.0 Hz,
1H), 7.62e7.64 (m, 2H), 7.51 (d, J¼8.4 Hz, 1H), 7.44 (d, J¼8.0 Hz, 1H),
7.36e7.40 (m, 1H), 7.30e7.33 (m, 1H), 7.22e7.26 (m, 1H), 7.18 (s, 1H).
4.4.10. (2-Methoxyphenyl)(1-(pyridin-2-yl)-1H-indol-2-yl)meth-
13C NMR (100 MHz, CDCl3):
d
185.7, 151.2, 149.3, 139.7, 138.2, 136.9,
anone (3j). (37.8 mg, 58%), white solid. Mp 35e37 ꢀC. 1H NMR
135.5, 131.6, 131.3, 127.7, 126.8, 126.7, 123.1, 122.4, 122.1, 120.9, 116.1,
(400 MHz, CDCl3): d 8.61e8.63 (m, 1H), 7.81e7.86 (m, 1H), 7.67
111.4. HRMS (ESI) m/z: calculated for
C
20H14BrN2O [MþH]þ:
(d, J¼8.0 Hz, 1H), 7.52e7.57 (m, 2H), 7.44e7.49 (m, 1H), 7.30e7.41
377.0284, found: 377.0288.
(m, 3H), 7.18e7.22 (m, 1H), 6.97e7.06 (m, 3H), 3.79 (s, 3H). 13C NMR
(100 MHz, CDCl3):
d 186.6, 157.8, 151.7, 148.9, 140.1, 137.8, 137.1,
4.4.4. (4-Chlorophenyl)(1-(pyridin-2-yl)-1H-indol-2-yl)methanone
132.2, 130.4, 128.8, 126.7, 126.7, 123.0, 122.2, 121.9, 121.8, 120.0,
116.5, 111.9, 111.4, 55.7. HRMS (ESI) m/z: calculated for C21H17N2O2
[MþH]þ: 329.1285, found: 329.1289.
(3d). (54.0 mg, 81%), white solid. Mp 36e38 ꢀC. 1H NMR (400 MHz,
CDCl3):
d
8.56e8.57 (m, 1H), 7.94 (d, J¼8.4 Hz, 2H), 7.84e7.89
(m, 1H), 7.73 (d, J¼7.6 Hz, 1H), 7.50 (d, J¼8.4 Hz, 1H), 7.43e7.47
(m, 3H), 7.35e7.39 (m, 1H), 7.29e7.32 (m, 1H), 7.22e7.26 (m, 1H),
4.4.11. (2-Fluorophenyl)(1-(pyridin-2-yl)-1H-indol-2-yl)methanone
7.17 (s, 1H). 13C NMR (100 MHz, CDCl3):
d
185.6, 151.2, 149.3, 139.6,
(3k). (28.5 mg, 45%), white solid. Mp 28e30 ꢀC. 1H NMR (400 MHz,
139.0, 138.2, 136.4, 135.6, 131.2, 128.6, 126.8, 126.7, 123.0, 122.4,
122.1,120.9,116.1,111.4. HRMS (ESI) m/z: calculated for C20H14ClN2O
[MþH]þ: 333.0789, found: 333.0793.
CDCl3): d 8.62e8.63 (m, 1H), 7.85e7.90 (m, 1H), 7.68e7.72 (m, 2H),
7.48e7.54 (m, 2H), 7.43 (d, J¼8.0 Hz, 1H), 7.32e7.39 (m, 2H),
7.22e7.26 (m, 2H), 7.14e7.20 (m, 2H). 13C NMR (100 MHz, CDCl3):
d
183.5, 160.3 (d, J¼253.0 Hz), 151.4, 149.2, 140.2, 138.1, 136.3, 133.2
4.4.5. (1-(Pyridin-2-yl)-1H-indol-2-yl)(p-tolyl)methanone
(d, J¼8.0 Hz), 131.0 (d, J¼2.0 Hz), 127.4, 127.3, 127.1, 126.7, 123.9
(d, J¼3.0 Hz), 123.2, 122.5, 122.0, 121.6, 117.1 (d, J¼2.0 Hz), 116.4
(d, J¼21.0 Hz), 111.7. HRMS (ESI) m/z: calculated for C20H14FN2O
[MþH]þ: 317.1085, found: 317.1082.
(3e). (55.1 mg, 88%), white solid. Mp 39e41 ꢀC. 1H NMR (400 MHz,
CDCl3):
d
8.55e8.57 (m, 1H), 7.92 (d, J¼8.0 Hz, 2H), 7.82e7.86
(m, 1H), 7.72 (d, J¼8.0 Hz, 1H), 7.54 (d, J¼8.4 Hz, 1H), 7.40
(d, J¼8.0 Hz, 1H), 7.33e7.38 (m, 1H), 7.27e7.30 (m, 3H), 7.20e7.24
(m, 1H), 7.18 (s, 1H), 2.44 (s, 3H). 13C NMR (100 MHz, CDCl3):
d
186.6,
4.4.12. (2-Chlorophenyl)(1-(pyridin-2-yl)-1H-indol-2-yl)methanone
151.5, 149.2, 143.4, 139.5, 138.0, 136.1, 135.5, 130.0, 129.0, 126.8,
(3l). (33.9 mg, 51%), white solid. Mp 34e36 ꢀC. 1H NMR (400 MHz,

7494
X.-B. Yan et al. / Tetrahedron 70 (2014) 7490e7495
CDCl3):
d
8.63e8.65 (m, 1H), 7.86e7.90 (m, 1H), 7.68 (d, J¼8.0 Hz,
151.3, 149.3, 144.0, 139.5, 138.1, 135.7, 134.0, 133.8, 128.0, 126.9,
126.5, 122.9, 122.3, 122.0, 121.0, 114.7, 111.5. HRMS (ESI) m/z: cal-
culated for C18H13N2OS [MþH]þ: 305.0743, found: 305.0741.
1H), 7.57e7.59 (m, 1H), 7.43e7.51 (m, 4H), 7.33e7.41 (m, 3H),
7.19e7.23 (m, 1H), 7.04 (s, 1H). 13C NMR (100 MHz, CDCl3):
d
185.5,
151.4, 149.1, 140.6, 138.4, 138.1, 135.8, 131.9, 131.4, 130.2, 130.0, 127.4,
126.6, 126.4, 123.2, 122.6, 122.1, 121.9, 117.9, 112.0. HRMS (ESI) m/z:
calculated for C20H14ClN2O [MþH]þ: 333.0789, found: 333.0791.
4.4.19. 1-(1-(Pyridin-2-yl)-1H-indol-2-yl)heptan-1-one
(3s). (48.6 mg, 79%), colorless oil. 1H NMR (400 MHz, CDCl3):
d
8.60e8.62 (m, 1H), 7.85e7.90 (m, 1H), 7.74 (d, J¼8.0 Hz, 1H), 7.43
4.4.13. (3,4-Dimethylphenyl)(1-(pyridin-2-yl)-1H-indol-2-yl)meth-
(s, 1H), 7.30e7.38 (m, 3H), 7.19e7.26 (m, 2H), 2.96 (t, J¼7.6 Hz, 2H),
anone (3m). (52.0 mg, 76%), white solid. Mp 168e170 ꢀC. 1H NMR
1.67e1.74 (m, 2H),1.26e1.38 (m, 6H), 0.88 (t, J¼6.8 Hz, 3H). 13C NMR
(400 MHz, CDCl3):
d
8.56e8.57 (m, 1H), 7.81e7.86 (m, 1H),
(100 MHz, CDCl3): d 192.8, 152.0, 149.2, 140.2, 138.0, 136.1, 126.6,
7.77e7.80 (m, 2H), 7.73 (d, J¼8.0 Hz, 1H), 7.55 (d, J¼8.4 Hz, 1H), 7.40
(d, J¼7.6 Hz, 1H), 7.33e7.37 (m, 1H), 7.26e7.30 (m, 1H), 7.21e7.25
(m, 2H), 7.18 (s, 1H), 2.34 (s, 3H), 2.32 (s, 3H). 13C NMR (100 MHz,
126.5, 122.8, 122.7, 122.0, 121.7, 112.9, 111.5, 39.6, 31.6, 29.0, 24.7,
22.5, 14.0. HRMS (ESI) m/z: calculated for C20H23N2O [MþH]þ:
307.1805, found: 307.1807.
CDCl3):
d 186.8, 151.5, 149.2, 142.2, 139.4, 138.0, 136.7, 136.2, 135.8,
131.0, 129.5, 127.8, 126.8,126.3, 122.9, 122.1, 121.8, 120.9, 115.6, 111.5,
20.0, 19.7. HRMS (ESI) m/z: calculated for C22H19N2O [MþH]þ:
327.1492, found: 327.1498.
4.4.20. Cyclohexyl(1-(pyridin-2-yl)-1H-indol-2-yl)methanone
(3t). (41.2 mg, 68%), colorless oil. 1H NMR (400 MHz, CDCl3):
d
8.61e8.62 (m, 1H), 7.84e7.88 (m, 1H), 7.74 (d, J¼8.0 Hz, 1H), 7.45
(s, 1H), 7.33e7.37 (m, 1H), 7.25e7.31 (m, 3H), 7.18e7.22 (m, 1H),
3.18e3.24 (m, 1H), 1.94e1.97 (m, 2H), 1.82e1.86 (m, 2H), 1.71e1.74
(m, 1H), 1.34e1.55 (m, 4H), 1.21e1.29 (m, 1H). 13C NMR (100 MHz,
4.4.14. (1,3-Dihydroisobenzofuran-5-yl)(1-(pyridin-2-yl)-1H-indol-
2-yl)methanone (3n). (56.7 mg, 83%), white solid. Mp 48e50 ꢀC. 1H
NMR (400 MHz, CDCl3):
d
8.55e8.57 (m, 1H), 7.83e7.87 (m, 1H),
CDCl3): d 196.2, 152.0, 149.1, 140.3, 138.0, 135.4, 126.5, 126.5, 122.8,
7.73 (d, J¼8.0 Hz, 1H), 7.67e7.69 (m, 1H), 7.55 (d, J¼8.4 Hz, 1H), 7.48
(d, J¼1.2 Hz, 1H), 7.41 (d, J¼7.6 Hz, 1H), 7.34e7.38 (m, 1H), 7.27e7.30
(m,1H), 7.21e7.25 (m,1H), 7.17 (s, 1H), 6.88 (d, J¼8.4 Hz,1H), 6.05 (s,
122.7, 122.0, 121.7, 112.6, 111.5, 47.4, 29.6, 25.8. HRMS (ESI) m/z:
calculated for C20H21N2O [MþH]þ: 305.1648, found: 305.1650.
2H). 13C NMR (100 MHz, CDCl3):
d
185.3, 151.7, 151.4, 149.3, 147.9,
4.4.21. 3-Methyl-1-(1-(pyridin-2-yl)-1H-indol-2-yl)but-2-en-1-one
139.3, 138.1, 136.0, 132.6, 126.8, 126.5, 126.3, 122.8, 122.1, 121.9,
(3u). (35.4 mg, 64%), white solid. Mp 88e90 ꢀC. 1H NMR (400 MHz,
120.8, 115.1, 111.4, 109.6, 107.7, 101.8. HRMS (ESI) m/z: calculated for
C
CDCl3):
d
8.61e8.63 (m, 1H), 7.85e7.89 (m, 1H), 7.73 (d, J¼8.0 Hz,
22H17N2O2 [MþH]þ: 341.1285, found: 341.1292.
1H), 7.30e7.37 (m, 5H), 7.18e7.22 (m, 1H), 6.78e6.79 (m, 1H), 2.14
(d, J¼0.8 Hz, 3H), 1.99 (d, J¼1.2 Hz, 3H). 13C NMR (100 MHz, CDCl3):
4.4.15. Naphthalen-2-yl(1-(pyridin-2-yl)-1H-indol-2-yl)methanone
d 182.8, 156.4, 152.1, 149.2, 140.0, 138.4, 138.0, 126.8, 126.2, 122.8,
(3o). (53.6 mg, 77%), white solid. Mp 52e54 ꢀC. 1H NMR (400 MHz,
122.5, 121.9, 121.8, 121.7, 112.2, 111.5, 28.0, 21.1. HRMS (ESI) m/z:
CDCl3):
d
8.60 (s, 1H), 8.56e8.57 (m, 1H), 8.03 (d, J¼8.4 Hz, 1H),
calculated for C18H17N2O [MþH]þ: 277.1335, found: 277.1333.
7.89e7.97 (m, 3H), 7.83e7.88 (m, 1H), 7.75 (d, J¼8.0 Hz, 1H),
7.53e7.63 (m, 3H), 7.47 (d, J¼8.0 Hz, 1H), 7.37e7.41 (m, 1H),
4.4.22. (E)-3,7-Dimethyl-1-(1-(pyridin-2-yl)-1H-indol-2-yl)octa-
7.23e7.30 (m, 3H). 13C NMR (100 MHz, CDCl3):
d
186.9, 151.4, 149.3,
2,6-dien-1-one (3v). (27.4 mg, 40%), white solid. Mp 36e38 ꢀC. 1H
139.6, 138.1, 136.2, 135.4, 132.3, 131.8, 129.5, 128.3, 127.8, 126.9,
126.7, 126.5, 125.4, 123.0, 122.2, 122.0, 120.9, 116.1, 111.5. HRMS (ESI)
m/z: calculated for C24H17N2O [MþH]þ: 349.1335, found: 349.1337.
NMR (400 MHz, CDCl3): d 8.61e8.63 (m,1H), 7.85e7.89 (m,1H), 7.73
(d, J¼8.0 Hz, 1H), 7.34e7.36 (m, 3H), 7.30e7.33 (m, 2H), 7.18e7.22
(m, 1H), 6.76 (s, 1H), 5.14e5.15 (m, 1H), 2.24 (br, 4H), 2.13
(d, J¼0.8 Hz, 3H), 1.73 (s, 3H), 1.64 (s, 3H). 13C NMR (100 MHz,
4.4.16. Naphthalen-1-yl(1-(pyridin-2-yl)-1H-indol-2-yl)methanone
CDCl3): d 183.1, 159.4, 152.1, 149.2, 140.0, 138.5, 138.0, 132.5, 126.8,
(3p). (49.7 mg, 71%), white solid. Mp 49e51 ꢀC. 1H NMR (400 MHz,
126.2, 123.2, 122.8, 122.5, 121.8, 121.7, 121.4, 112.3, 111.5, 41.4, 26.2,
25.7, 19.7, 17.8. HRMS (ESI) m/z: calculated for C23H25N2O [MþH]þ:
345.1961, found: 345.1960.
CDCl3): d 8.59e8.60 (m, 1H), 8.36e8.39 (m, 1H), 7.96e8.01 (m, 2H),
7.84e7.90 (m, 2H), 7.66 (d, J¼8.0 Hz, 1H), 7.48e7.53 (m, 5H),
7.35e7.39 (m, 1H), 7.29e7.32 (m, 1H), 7.19e7.24 (m, 1H), 7.06
(d, J¼0.4 Hz, 1H). 13C NMR (100 MHz, CDCl3):
d
188.2, 151.6, 149.3,
4.4.23. (5-Bromo-1-(pyridin-2-yl)-1H-indol-2-yl)(phenyl)meth-
140.1, 138.1, 137.7, 136.0, 133.7, 132.0, 131.0, 129.1, 128.2, 127.4, 126.9,
126.7, 126.4, 125.7, 124.1, 123.1, 122.4, 122.0, 121.3, 117.2, 111.6. HRMS
(ESI) m/z: calculated for C24H17N2O [MþH]þ: 349.1335, found:
349.1339.
anone (4a). (58.9 mg, 78%), white solid. Mp 40e42 ꢀC. 1H NMR
(400 MHz, CDCl3):
d 8.56e8.57 (m, 1H), 7.97e7.99 (m, 2H),
7.84e7.88 (m, 2H), 7.59e7.63 (m, 1H), 7.48e7.51 (m, 2H), 7.43
(s, 2H), 7.38 (d, J¼8.0 Hz, 1H), 7.30e7.33 (m, 1H), 7.11 (s, 1H). 13C
NMR (100 MHz, CDCl3):
d 186.7, 151.0, 149.3, 138.2, 138.0, 137.7,
4.4.17. (5-Methylfuran-2-yl)(1-(pyridin-2-yl)-1H-indol-2-yl)meth-
136.7, 132.9, 129.9, 129.3, 128.4, 128.3, 125.2, 122.5, 120.9, 114.9,
114.6, 113.1. HRMS (ESI) m/z: calculated for C20H14BrN2O [MþH]þ:
377.0284, found: 377.0281.
anone (3q). (38.6 mg, 64%), white solid. Mp 30e32 ꢀC. 1H NMR
(400 MHz, CDCl3):
d 8.57e8.58 (m, 1H), 7.84e7.88 (m, 1H), 7.76
(d, J¼7.6 Hz,1H), 7.50e7.52 (m, 2H), 7.41 (d, J¼8.0 Hz,1H), 7.33e7.37
(m,1H), 7.28e7.31 (m, 2H), 7.22e7.26 (m,1H), 6.22 (d, J¼3.2 Hz,1H),
4.4.24. (6-Chloro-1-(pyridin-2-yl)-1H-indol-2-yl)(phenyl)meth-
2.44 (s, 3H). 13C NMR (100 MHz, CDCl3):
d
172.9, 158.4, 151.5, 151.4,
anone (4b). (59.8 mg, 90%), white solid. Mp 116e118 ꢀC. 1H NMR
149.3, 139.4, 138.0, 135.3, 127.0, 126.2, 122.9, 122.2, 121.9, 121.8,
(400 MHz, CDCl3): d 8.58e8.60 (m, 1H), 7.97e7.99 (m, 2H),
121.0, 113.9, 111.5, 109.1, 14.2. HRMS (ESI) m/z: calculated for
C
7.85e7.89 (m, 1H), 7.58e7.64 (m, 2H), 7.54 (d, J¼0.8 Hz, 1H),
7.47e7.51 (m, 2H), 7.39 (d, J¼8.0 Hz, 1H), 7.31e7.35 (m, 1H),
7.18e7.21 (m, 1H), 7.16 (d, J¼0.4 Hz, 1H). 13C NMR (100 MHz, CDCl3):
19H15N2O2 [MþH]þ: 303.1128, found: 303.1125.
4.4.18. (1-(Pyridin-2-yl)-1H-indol-2-yl)(thiophen-2-yl)methanone
d 186.5, 150.9, 149.3, 139.8, 138.3, 137.8, 136.5, 132.8, 132.6, 129.8,
(3r). (45.2 mg, 74%), white solid. Mp 31e33 ꢀC. 1H NMR (400 MHz,
128.3, 125.2, 123.9, 122.9, 122.6, 121.0, 115.8, 111.6. HRMS (ESI) m/z:
CDCl3):
d 8.57e8.58 (m, 1H), 7.95e7.96 (m, 1H), 7.85e7.89 (m, 1H),
calculated for C20H14ClN2O [MþH]þ: 333.0789, found: 333.0793.
7.76 (d, J¼8.0 Hz, 1H), 7.70e7.71 (m, 1H), 7.52e7.54 (m, 1H),
7.42e7.44 (m, 2H), 7.35e7.39 (m, 1H), 7.29e7.32 (m, 1H), 7.25e7.27
4.4.25. (5-Methoxy-1-(pyridin-2-yl)-1H-indol-2-yl)(phenyl)meth-
(m, 1H), 7.18e7.21 (m, 1H). 13C NMR (100 MHz, CDCl3):
d
178.4,
anone (4c). (46.5 mg, 71%), white solid. Mp 42e44 ꢀC. 1H NMR

X.-B. Yan et al. / Tetrahedron 70 (2014) 7490e7495
7495
(400 MHz, CDCl3):
d
8.56e8.57 (m, 1H), 8.00 (d, J¼7.2 Hz, 2H),
128.5, 127.7, 126.5, 123.2, 121.0, 112.8, 112.2. HRMS (ESI) m/z: cal-
culated for C15H12NO [MþH]þ: 222.0913, found: 222.0907.
7.81e7.86 (m, 1H), 7.58e7.61 (m, 1H), 7.45e7.50 (m, 3H), 7.38
(d, J¼8.0 Hz, 1H), 7.27e7.30 (m, 1H), 7.11e7.13 (m, 2H), 7.02e7.05
(m, 1H), 3.86 (s, 3H). 13C NMR (100 MHz, CDCl3):
d 186.7, 155.4,
Acknowledgements
151.5, 149.2, 138.1, 138.0, 136.1, 135.1, 132.6, 129.8, 128.2, 127.2, 122.1,
120.9, 117.8, 115.9, 112.6, 102.9, 55.6. HRMS (ESI) m/z: calculated for
C
We thank the National Natural Science Foundation of China (No.
21072081 and 201302076) for financial support.
21H17N2O2 [MþH]þ: 329.1285, found: 329.1289.
4.4.26. Methyl 2-benzoyl-1-(pyridin-2-yl)-1H-indole-6-carboxylate
Supplementary data
(4d). (48.1 mg, 68%), white solid. Mp 120e122 ꢀC. 1H NMR
(400 MHz, CDCl3):
(m, 2H), 7.89e7.94 (m, 2H), 7.76e7.78 (m, 1H), 7.60e7.64 (m, 1H),
7.48e7.52 (m, 3H), 7.33e7.36 (m, 1H), 7.20 (s, 1H), 3.92 (s, 3H). 13
NMR (100 MHz, CDCl3): 186.9, 167.3, 150.7, 149.5, 138.6, 138.4,
d 8.56e8.58 (m, 1H), 8.23 (s, 1H), 8.00e8.02
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2014.08.025.
C
d
References and notes
138.4,137.6,133.0,130.1,129.9,128.4,127.7, 122.7,122.6,120.9,114.7,
113.7, 52.2. HRMS (ESI) m/z: calculated for C22H17N2O3 [MþH]þ:
357.1234, found: 357.1231.
1. Selected reviews, see: (a) Chen, X.; Engle, K. M.; Wang, D.-H.; Yu, J.-Q. Angew.
Chem., Int. Ed. 2009, 48, 5094e5115; (b) Daugulis, O.; Do, H.-Q.; Shabashov, D.
Acc. Chem. Res. 2009, 42, 1074e1086; (c) Lyons, T. W.; Sanford, M. S. Chem. Rev.
2010, 110, 1147e1169; (d) Ackermann, L. Chem. Rev. 2011, 111, 1315e1345; (e) Liu,
C.; Zhang, H.; Shi, W.; Lei, A. Chem. Rev. 2011, 111, 1780e1824; (f) Wencel-Delord,
4.4.27. (3-Methyl-1-(pyridin-2-yl)-1H-indol-2-yl)(phenyl)meth-
€
J.; Droge, T.; Liu, F.; Glorius, F. Chem. Soc. Rev. 2011, 40, 4740e4761; (g) Yeung, C.
anone (4e). (35.1 mg, 56%), white solid. Mp 44e46 ꢀC. 1H NMR
S.; Dong, V. M. Chem. Rev. 2011, 111, 1215e1292; (h) Colby, D. A.; Tsai, A. S.;
Bergman, R. G.; Ellman, J. A. Acc. Chem. Res. 2012, 45, 814e825; (i) Song, G.;
Wang, F.; Li, X. Chem. Soc. Rev. 2012, 41, 3651e3678; (j) Patureau, F. W.; Wencel-
Delord, J.; Glorius, F. Aldrichimica Acta 2012, 45, 31e41; (k) Pan, C.; Jia, X.;
Cheng, J. Synthesis 2012, 44, 677e685; (l) Mei, T.-S.; Kou, L.; Ma, S.; Engle, K. M.;
Yu, J.-Q. Synthesis 2012, 44, 1778e1791.
(400 MHz, CDCl3):
d 8.37e8.39 (m, 1H), 7.80e7.82 (m, 2H),
7.67e7.73 (m, 3H), 7.44e7.48 (m, 1H), 7.31e7.41 (m, 4H), 7.26e7.27
(m, 1H), 7.05e7.08 (m, 1H), 2.35 (s, 3H). 13C NMR (100 MHz, CDCl3):
d
189.6, 151.3, 149.1, 138.9, 137.9, 137.4, 133.7, 132.6, 129.5, 128.9,
2. Jia, X.; Zhang, S.; Wang, W.; Luo, F.; Cheng, J. Org. Lett. 2009, 11, 3120e3123.
128.3, 126.1, 121.5, 121.5, 121.0, 120.8, 119.4, 111.3, 10.2. HRMS (ESI)
ꢀ
m/z: calculated for C21H17N2O [MþH]þ: 313.1335, found: 313.1336.
3. (a) Basle, O.; Bidange, J.; Shuai, Q.; Li, C.-J. Adv. Synth. Catal. 2010, 352,
ꢀ
1145e1149; (b) Xiao, F.; Shuai, Q.; Zhao, F.; Basle, O.; Deng, G.; Li, C.-J. Org. Lett.
2011, 13, 1614e1617.
4.4.28. 2-Benzoyl-1-(pyridin-2-yl)-1H-indole-3-carbonitrile
4. (a) Wu, Y.; Li, B.; Mao, F.; Li, X.; Kwong, F. Y. Org. Lett. 2011, 13, 3258e3261; (b)
(4f). (29.9 mg, 46%), white solid. Mp 60e62 ꢀC. 1H NMR (400 MHz,
Li, C.; Wang, L.; Li, P.; Zhou, W. Chem.dEur. J. 2011, 17, 10208e10212; (c) Chan,
ꢀ
C.-W.; Zhou, Z.; Yu, W.-Y. Adv. Synth. Catal. 2011, 353, 2999e3006; (d) Szabo, F.;
CDCl3):
7.62e7.66 (m, 2H), 7.47e7.54 (m, 4H), 7.42e7.46 (m, 1H), 7.30e7.33
(m, 1H). 13C NMR (100 MHz, CDCl3):
186.4, 149.7, 149.3, 141.3,
d 8.45e8.47 (m, 1H), 7.95e7.97 (m, 2H), 7.87e7.91 (m, 2H),
ꢀ
ꢀ
Daru, J.; Simko, D.; Nagy, T. Z.; Stirling, A.; Novak, Z. Adv. Synth. Catal. 2013, 355,
685e691.
5. Chan, C.-W.; Zhou, Z.; Chan, A. S. C.; Yu, W.-Y. Org. Lett. 2010, 12, 3926e3929.
6. (a) Li, H.; Li, P.; Wang, L. Org. Lett. 2013, 15, 620e623; (b) Xiong, F.; Qian, C.; Lin,
D.; Zeng, W.; Lu, X. Org. Lett. 2013, 15, 5444e5447.
7. Sharma, S.; Park, J.; Park, E.; Kim, A.; Kim, M.; Kwak, J. H.; Jung, Y. H.; Kim, I. S.
Adv. Synth. Catal. 2013, 355, 332e336.
8. Selected recent examples, see: (a) Li, M.; Ge, H. Org. Lett. 2010, 12, 3464e3467;
(b) Fang, P.; Li, M.; Ge, H. J. Am. Chem. Soc. 2010, 132, 11898e11899; (c) Wang, H.;
Guo, L.-N.; Duan, X.-H. Org. Lett. 2012, 14, 4358e4361; (d) Kim, M.; Park, J.;
Sharma, S.; Kim, A.; Park, E.; Kwak, J. H.; Jung, Y. H.; Kim, I. S. Chem. Commun.
2013, 925e927; (e) Yang, Z.; Chen, X.; Liu, J.; Gui, Q.; Xie, K.; Li, M.; Tan, Z. Chem.
Commun. 2013, 1560e1562.
d
138.6, 136.5, 136.4, 134.3, 130.1, 128.7, 127.2, 127.1, 124.1, 123.3, 121.0,
120.1, 113.8, 112.0, 93.5. HRMS (ESI) m/z: calculated for C21H14N3O
[MþH]þ: 324.1131, found: 324.1127.
4.4.29. Phenyl(1-(pyrimidin-2-yl)-1H-indol-2-yl)methanone
(4g). (49.8 mg, 83%), white solid. Mp 121e123 ꢀC. 1H NMR
(400 MHz, CDCl3):
d
8.63 (d, J¼4.8 Hz, 2H), 8.39 (d, J¼8.8 Hz, 1H),
7.97 (d, J¼7.6 Hz, 2H), 7.70 (d, J¼8.0 Hz, 1H), 7.53e7.56 (m, 1H),
7.42e7.46 (m, 3H), 7.27e7.31 (m,1H), 7.13 (s, 1H), 7.04e7.06 (m,1H).
9. Zhou, W.; Li, H.; Wang, L. Org. Lett. 2012, 14, 4594e4597.
10. (a) Sundberg, R. J. Indoles; Academic: New York, NY, 1996; (b) Eicher, T.;
Hauptmann, S. The Chemistry of Heterocycles; Wiley-VCH: Weinheim, Germany,
2003; (c) Humphrey, G. R.; Kuethe, J. T. Chem. Rev. 2006, 106, 2875e2911; (d)
Higuchi, K.; Kawasaki, T. Nat. Prod. Rep. 2007, 24, 843e868; (e) Kochanowska-
Karamyan, A. J.; Hamann, M. T. Chem. Rev. 2010, 110, 4489e4497.
11. (a) Willson, T. M.; Brown, P. J.; Sternbach, D. D.; Henke, B. R. J. Med. Chem. 2000,
43, 527e550; (b) Mahboobi, S.; Teller, S.; Pongratz, H.; Hufsky, H.; Sellmer, A.;
13C NMR (100 MHz, CDCl3):
d 187.5, 157.9, 157.2, 138.2, 137.9, 137.1,
132.7, 129.5, 128.3, 127.9, 126.5, 122.8, 122.5, 117.4, 115.4, 114.1.
HRMS (ESI) m/z: calculated for C19H14N3O [MþH]þ: 300.1131,
found: 300.1127.
€
Botzki, A.; Uecker, A.; Beckers, T.; Baasner, S.; Schachtele, C.; Uberall, F.; Kassack,
€
4.4.30. (1-(Pyridin-2-yl)-1H-pyrrole-2,5-diyl)bis(phenylmethanone)
M. U.; Dove, S.; Bohmer, F. D. J. Med. Chem. 2002, 45, 1002e1018; (c) Brancale, A.;
(4h). (54.3 mg, 77%), white solid. Mp 110e112 ꢀC. 1H NMR
Silvestri, R. Med. Res. Rev. 2007, 27, 209e238; (d) Mahboobi, S.; Sellmer, A.;
Hocher, H.; Garhammer, C.; Pongratz, H.; Maier, T. T.; Ciossek, T.; Beckers, T. J.
Med. Chem. 2007, 50, 4405e4418.
(400 MHz, CDCl3):
7.79e7.84 (m, 1H), 7.57e7.60 (m, 2H), 7.44e7.49 (m, 5H), 7.32e7.36
(m, 1H), 6.83 (s, 2H). 13C NMR (100 MHz, CDCl3):
185.9, 151.8,
d 8.46e8.48 (m, 1H), 7.90e7.92 (m, 4H),
12. Zhou, B.; Yang, Y.; Li, Y. Chem. Commun. 2012, 5163e5165.
13. Pan, C.; Jin, H.; Liu, X.; Cheng, Y.; Zhu, C. Chem. Commun. 2013, 2933e2935.
14. The roles of PivOH, see: (a) Li, D.; Wang, M.; Liu, J.; Zhao, Q.; Wang, L. Chem.
Commun. 2013, 3640e3642; (b) Li, Y.; Wang, W.-H.; He, K.-H.; Shi, Z.-J. Or-
ganometallics 2012, 31, 4397e4400.
15. (a) Chu, J.-H.; Wu, C.-C.; Chang, D.-H.; Lee, Y.-M.; Wu, M.-J. Organometallics
2013, 32, 272e282; (b) Jana, C. K.; Grimme, S.; Studer, A. Chem.dEur. J. 2009, 15,
9078e9084.
16. (a) Powers, D. C.; Geibel, M. A. L.; Klein, J. E. M. N.; Ritter, T. J. Am. Chem. Soc.
2009, 131, 17050e17051; (b) Powers, D. C.; Ritter, T. Nat. Chem. 2009, 1,
302e309.
17. (a) Deprez, N. R.; Sanford, M. S. J. Am. Chem. Soc. 2009, 131, 11234e11241; (b)
Racowski, J. M.; Dick, A. R.; Sanford, M. S. J. Am. Chem. Soc. 2009, 131,
10974e10983.
d
148.5, 137.9, 137.5, 136.0, 132.8, 129.7, 128.3, 123.2, 122.4, 119.4.
HRMS (ESI) m/z: calculated for C23H17N2O2 [MþH]þ: 353.1285,
found: 353.1284.
4.4.31. (1H-Indol-2-yl)(phenyl)methanone (3a0). (29.4 mg, 67%),
white solid. Mp 151e153 ꢀC. 1H NMR (400 MHz, CDCl3):
d 9.44
(s, 1H), 7.99e8.01 (m, 2H), 7.71e7.73 (m, 1H), 7.61e7.65 (m, 1H),
7.48e7.56 (m, 3H), 7.36e7.40 (m, 1H), 7.15e7.19 (m, 2H), 7.16 (s, 1H).
13C NMR (100 MHz, CDCl3):
d 187.2, 138.0, 137.5, 134.3, 132.4, 129.2,