Palladium-catalyzed one-pot synthesis of benzo[b][1,6]naphthyridines via Sonogashira coupling and annulation reactions from 2-chloroquinoline-3- carbonitriles

Article abstract of DOI:10.1016/j.tet.2013.08.072

Palladium-catalyzed one-pot synthesis of 1,3-disubstituted benzo[b][1,6]naphthyridines and [1,6]naphthyridines has been described from easily accessible precursors, 2-chloroquinoline-3-carbonitriles and 2-chloropyrido-3-carbonitrile via sequential additions of palladium-catalyst for Sonogashira-coupling and the following annulations in good to excellent yields. A plausible mechanism for annulation is discussed.

Full text of DOI:10.1016/j.tet.2013.08.072

Tetrahedron 69 (2013) 9443e9450
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Palladium-catalyzed one-pot synthesis of benzo[b][1,6]
naphthyridines via Sonogashira coupling and annulation reactions
from 2-chloroquinoline-3-carbonitriles
*
Radhey M. Singh , Ritush Kumar, Neha Sharma, Mrityunjaya Asthana
Department of Chemistry, Centre of Advance Studies, Banaras Hindu University, Varanasi, U.P., India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 22 June 2013
Received in revised form 27 August 2013
Accepted 29 August 2013
Available online 5 September 2013
Palladium-catalyzed one-pot synthesis of 1,3-disubstituted benzo[b][1,6]naphthyridines and [1,6]naph-
thyridines has been described from easily accessible precursors, 2-chloroquinoline-3-carbonitriles and 2-
chloropyrido-3-carbonitrile via sequential additions of palladium-catalyst for Sonogashira-coupling and
the following annulations in good to excellent yields. A plausible mechanism for annulation is discussed.
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Palladium
One-pot
2-Chloroquinoline-3-carbonitrile
Intramolecular
[1,6]Naphthyridine
1. Introduction
synthesis of [1,6]naphthyridines and their benzo analogues.1,3a,6
Kozlowski and Larock et al. have reported [1,6]naphthyridines from
[1,6]Naphthyridine and their benzo-fused analogues are present
in numerous products of marine alkaloids (Fig. 1)1 and display wide
range of physiological activities, such as anti-tumour and anti-
inflammatory activities,2 HIV-1 integrase inhibitors containing
metal binding motif,3 AKt1 and AKt2 inhibitors,4 cytotoxic activity.5
Consequently, various synthetic routes have been developed for the
4-aminopyridine and allyl alcohol using palladium methodology.7
Rudys et al. have reported three component reactions to benzo[b]
[1,6]naphthyridines.8 Sakamoto et al. have reported the synthesis of
[1,6]naphthyridines from o-alkynylpyridinecarboxaldehydes with
ammonia.9 We have also reported benzo[b][1,6]naphthyridines from
the corresponding quinoline-3-carboxaldehyde analogues using
similar reaction.10
In recent years, inter- and intramolecular palladium-catalyzed
annulation reactions of internal and terminal alkynes with aryl or
heteroaryl halides possessing nucleophilic functional group next to
halide have emerged as a versatile and efficient route to the synthesis
of various heterocycles and fused-heterocycles.11 The palladium-
catalyzed annulations of N-tert-butyl o-iodobenzaldimine and N-
tert-butyl o-iodoindolealdimine with internal and terminal alkynes
have been reported to isoquinolines and pyrido-fused indoles, re-
spectively.12 However, similar Pd-catalyzed annulations with o-halo
aryl/heteroaryl carbonitriles have been less studied. Larock et al. have
reported Pd-catalyzed annulation of 2-iodobenzonitrilewith internal
alkynes to 2,3-diarylindenones (Scheme 1A).13 Wei et al. have re-
ported Pd-catalyzed intramolecular annulation of o-phenylethynyl
benzonitriles with aryl iodide to isoindoles in low yields (Scheme
1B).14 However, Pd-catalyzed intramolecular annulations of corre-
sponding hetero analogues have not been studied. Recently, we have
reported Pd-catalyzed intramolecular cyclization/annulation of
SO3
NMe3
O
R
N
N
Br
OMe
OMe
OMe
OMe
N
N
OR1
MeO
MeO
N
N
HN
H
OMe
N
N
N
H
(1) Aaptamine (R= H, R1=Me)
(2) Isoaaptamine (R=Me, R1= H)
Nakijinamine C (1)
Suberitine
(a)
(b)
(c)
Fig. 1. Significant examples of marine alkaloids containing [1,6]naphthyridine
skeletons.
* Corresponding author. Tel.: þ91 542 6702482; fax: þ91 542 2368127; e-mail
addresses: rmohan@bhu.ac.in, rmohanbhu@gmail.com (R.M. Singh).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.08.072

9444
R.M. Singh et al. / Tetrahedron 69 (2013) 9443e9450
alkene and alkyne to the synthesis of cyclopenta- and pyrano-fused
quinolines, respectively.15 Since Sonogashira coupling reaction pro-
ceeded with the aid of Pd-catalyst, we envisioned that two-step Pd-
catalyzed Sonogashira coupling and annulation process could pro-
ceed in one-pot from 2-chloroquinoline-3-carbonitriles and pyridine
analogues to afford benzo[b][1,6]naphthyridines and [1,6]naphthyr-
idines. Thus, we herein report Pd-catalyzed one-pot synthesis of
benzo[b][1,6]naphthyridines and [1,6]naphthyridines from 2-
chloroquinoline-3-carbonitriles and their pyridine-analogues with
terminal alkynes by sequential addition of palladium-catalyst in the
Sonogashira-coupling and annulation reaction, respectively.
synthesize benzo[b][1,6]naphthyridines 3 (Scheme 1). The re-
action of 1a (0.25 mmol) with phenylacetylene (0.26 mmol) using
10 mol % of Pd(OAc)2, 20 mol % of PPh3 and 2 equiv Et3N in
acetonitrile at 80 ꢀC under N2 for Sonogashira coupling and
subsequent annulation by addition of methanol as nucleophile
and solvent at same temperature in aerobic atmosphere for
overnight, failed to provide the cyclized product 3a (Table 1, entry
1). However, adding 1.5 equiv of K2CO3 along with methanol in
annulation step under similar conditions afforded the cyclized
product 3a in 75% yield. This result could be explained by con-
sidering that methoxide ion acts as nucleophile in annulation
process (entry 2). Encouraged by this observation, we further
examined the sequential reaction using 5 mol % of Pd(OAc)2,
10 mol % of PPh3 and 2 equiv of Et3N in acetonitrile at 80 ꢀC under
N2 atm for Sonogashira coupling and 5 mol % of Pd(OAc)2,
10 mol % of PPh3 and 1.5 equiv K2CO3 in methanol at same tem-
perature in aerobic conditions for annulation step. The reaction
proceeded smoothly and provided the cyclized product 3a in 80%
yield (entry 3). Thus, considering sequential additions of
palladium-catalyst as our reaction conditions, we next examined
other parameters, such as other available palladium-catalysts and
bases to find an optimal reaction conditions for annulation step
(entries 4e10). The available palladium catalysts PdCl2 and
Pd(dba)2 were found less effective (entries 4 and 5). Using PdCl2
in Sonogashira coupling and Pd(OAc)2 or PdCl2 for annulations,
adversely affected the yield as well as the rate of reaction (entries
6 and 7). Among the inorganic bases, K3PO4 and Cs2CO3 were
tested. K3PO4 afforded the product 3a in same yield (entry 8)
whereas Cs2CO3 was found ineffective (entry 9). Further on in-
creasing the amount of K2CO3 to 2 equiv did not improve the yield
of 3a (entry 10). The annulation reaction using Sonogashira
coupling product 2a did not show significant variation in the yield
of 3a (entry 11).
(A) Larock’s work
O
CN
Pd(dba)2/Et3N
Ph
+
Ph
Ph
DMF/H2O, 1300C
24 h, N2 atm
I
R
R
Ph
47-96%
(B) Wei’s work
OCH3
N
OCH3
N
CN
ArI, Pd(PPh3)4
+
CH3ONa, CH3OH
24-48 h,
R
Ar
R
R
N
2 atm
Ar
18-56%
0%
R = Ph
(C) This work
OR"
N
CN
CN
Pd(OAc)2/ Ph3P/
Et3N,CH3CN
Pd(OAc)2/ Ph3P
K2CO3, R"OH
80°C, 2-7 h
air
N
Cl
N
R'
R
N
R
R
80oC,
R'
R'
3
2
1
2.5-12 h, N2 atm
72-85%
Scheme 1. Reactions on carbonitriles.
2. Results and discussion
Based on the sequential additions using 5 mol % of Pd(OAc)2,
10 mol % of PPh3 and 2 equiv of Et3N in acetonitrile at 80 ꢀC under
N2 atm for Sonogashira coupling followed by further addition of
5 mol % of Pd(OAc)2, 10 mol % of PPh3 and 1.5 equiv K2CO3 in
methanol under aerobic conditions for 0.25 mmol of 1a with
Initially, we examined the reaction of 2-chloroquinoline-3-
carbonitriles 1 with terminal alkynes using our earlier reported
palladium-catalyzed annulation conditions15b with a view to
Table 1
Optimization table for one-pot sequential Sonogashira coupling and intramolecular cyclization of 2-chloroquinoline-3-carbonitrile
OMe
N
CN
CN
Cl
Pd(OAc)2/ Ph3P/
Et3N,CH3CN
Pd(OAc)2/ Ph3P
Base, MeOH
80.°C, air
N
N
N
Ph
80 °C,
N2 atm
3 hr
Ph
Ph
Entry
Sonogashira couplinga
Catalyst (mol %)
Annulation reaction
Catalyst (mol %)
Time (h)b
Yieldc (%) (4a)
Ligand (mol %)
Base (equiv)
Ligand (mol %)
Base (equiv)
1
2
3
4
5
6
7
8
Pd(OAc)2 (10)
Pd(OAc)2 (10)
Pd(OAc)2 (5)
Pd(OAc)2 (10)
Pd(OAc)2 (5)
PdCl2 (5)
Ph3P (20)
Ph3P (20)
Ph3P (10)
Ph3P (20)
Ph3P (10)
Ph3P (10)
Ph3P (10)
Ph3P (10)
Ph3P (10)
Ph3P (10)
d
Et3N (2)
Et3N (2)
Et3N (2)
Et3N (2)
Et3N (2)
Et3N (2)
Et3N (2)
Et3N (2)
Et3N (2)
Et3N (2)
d
d
d
d
Overnight
3.5
3
5
7
3.5
6
3
21
3
3.5
Nrd
75
80
65
45
80
60
80
Trace
79
d
d
K2CO3 (1.5)
K2CO3 (1.5)
K2CO3 (1.5)
K2CO3 (1.5)
K2CO3 (1.5)
K2CO3 (1.5)
K3PO4 (1.5)
Cs2CO3 (1.5)
K2CO3 (2)
K2CO3 (1.5)
Pd(OAc)2 (5)
PdCl2 (5)
Pd(dba)2 (5)
Pd(OAc)2 (5)
PdCl2 (5)
Pd(OAc)2 (5)
Pd(OAc)2 (5)
Pd(OAc)2 (5)
Pd(OAc)2 (5)
Ph3P (10)
Ph3P (10)
Ph3P (10)
Ph3P (10)
Ph3P (10)
Ph3P (10)
Ph3P (10)
Ph3P (10)
Ph3P (10)
PdCl2 (5)
Pd(OAc)2 (5)
Pd(OAc)2 (5)
Pd(OAc)2 (5)
d
9
10
11
82
The bold value signifies the optimized condition in the reaction.
a
Time for Sonogashira coupling is 3 h.
Annulation time.
Isolated yields.
Nr¼no reaction.
b
c
d

R.M. Singh et al. / Tetrahedron 69 (2013) 9443e9450
9445
0.26 mmol of phenylacetylene gave the best yield of the annulated
product 3a and this is used as our optimized reaction conditions
(entry 3).
4. Experimental section
4.1. General
To explore the generality and scope of this coupling-
annulation processes, the reactions of 1a with phenylacetylenes
bearing different substituents on phenyl ring were examined
under optimized reaction conditions. The reactions proceeded
smoothly and afforded the annulated products 3(abeae) in good
yields. Results are summarized in Table 2 (entries 1e5). No sig-
nificant variations in the yields were found with phenylacetylene
ring bearing electron donating (entries 2e4) or electron with-
drawing group (entry 5). However, rate was higher with phe-
nylacetylene bearing electron withdrawing group (as monitored
by TLC at regular intervals of 30 min). Further annulation with
acetylene bearing alkyl group afforded the lower yield in less
time (entry 6). To further explore the scope of annulations, the
Unless otherwise stated, all reactions were performed under
nitrogen and air successively. Solvents were purified following
standard literature procedures. Melting points were measured in
an open capillary tube and are uncorrected. 1H (300 MHz) and 13
C
(75 MHz) NMR spectra were recorded 300 MHz spectrometer.
Multiplicities are given as: s (singlet), br s (broad singlet), d (dou-
blet), t (triplet), dd (doublet of doublets) or m (multiplet). The
chemical shifts (d parts per million) and coupling constants (J
Hertz) are reported in the standard fashion with reference to either
internal tetramethylsilane (for 1H) or the central line (77.0 ppm) of
CDCl3 (for 13C). Moisture and residual peak of CDCl3 appear at
d 1.5
and 7.2, respectively, in 1H NMR. High resolution mass spectra
(HRMS) were obtained on micro TOF QII high-resolution mass
spectrometer (ESI) and 6200 series TOF/6500 SRIES QTOF B.05.00
(B5042.0). 2-chloroquinoline-3-carbonitrile 1(aeg) was synthe-
sized by our previously reported method.17 Single-crystal X-ray
data was collected for compound 3ac.
reaction of compound
4 with phenylacetylene and phenyl-
acetylene bearing electron donating and withdrawing groups
were examined under optimized conditions and afforded [1,6]
naphthyridines 5(aec) in good yields (Table 2, entries 7e9). The
effects of electron donating and electron withdrawing groups on
the rate and yields were similar to quinoline analogues (entries 8
and 9).
4.2. General procedure for synthesis of benzo[b][1,6]
To further explore the generality and scope of the annulation
reactions, we examined the reaction of various substituted 2-
chloroquinoline-3-carbonitriles 1(beh) with phenylacetylene. The
reactions proceeded smoothly and afforded the annulated prod-
ucts, 1-methoxy-3-phenylbenzo[b][1,6]naphthyridines 3(beh) in
good yields (Table 2, entries 10e16). An electron-donating groups
on phenyl ring in quinolines are less reactive than electron with-
drawing groups, however no significant variations are found in the
yields of the annulated products (entries 10e16).
To further explore the generality and scope of this annulation,
various alcohols as nucleophiles and solvents were tested with
substrate 1a using optimized conditions. Primary alcohols, such as
EtOH and n-BuOH, reacted well and provided good yields of desired
benzo[b][1,6]naphthyridines (entries 17 and 18). It is noteworthy
that annulation of 2a failed with i-PrOH and t-BuOH, which could
be attributed to steric hindrance or dehydration of alcohols (entries
19 and 20). Further, phenol was also tested for annulation, the rate
of reaction was slower and afforded cyclized product 3ai in 72%
(entry 21) and could be attributed to weak nucleophilicity of
phenoxide ion.
naphthyridines
A
mixture of substituted 2-chloroquinoline-3-carbonitriles
1(aeh) (0.25 mmol), phenylacetylene (0.26 mmol), Pd(OAc)2
(5 mol %) and PPh3 (10 mol %) in CH3CN (2 mL) and TEA (2 equiv)
were stirred under N2 at 80 ꢀC, after completion of reaction (as
monitored by TLC), solvent was evaporated and further Pd(OAc)2
(5 mol %), PPh3 (10 mol %), K2CO3 (1.5 equiv) and 4 mL of methanol
were added under aerobic condition at 80 ꢀC upto completion. The
mixture was concentrated in vacuo and residue was purified by
column chromatography on silica gel using EtOAc/hexane as eluent.
4.2.1. 1-Methoxy-3-phenyl-benzo[b][1,6]naphthyridine (3a). Light
green solid; yield: 57.2 mg (80%); mp 106e107 ꢀC; Rf¼0.35 (05:95
EtOAc/hexane); 1H NMR (300 MHz, CDCl3):
d
¼4.33 (s, 3H),
7.43e7.59 (m, 3H), 7.86 (t, J¼7.5 Hz, 1H), 8.04 (d, J¼7.8 Hz, 2H),
8.18e8.32 (m, 3H), 9.18 (s, 1H); 13C NMR (75 MHz, CDCl3):
d¼54.1,
110.9, 113.9, 125.8, 126.6, 126.8, 128.5, 128.7, 129.0, 129.2, 132.2,
134.3, 138.7, 151.1, 151.5, 152.8, 161.1; IR (KBr, cmꢁ1): 2926; HRMS
calcd for C19H15N2O [MþH]þ 287.1184, found 287.1174.
A single X-ray crystallographic analysis of 3ac was performed to
establish the structure of annulated products.16 An ORTEP repre-
sentation of the molecule 3ac is given in Fig. 2.
A plausible mechanism for Pd-catalyzed cyclization is illus-
trated in Scheme 2. In this reaction Pd(OAc)2 plays dual role:11d (1)
as a Lewis acid, which forms complex A with the nitrogen atom of
the cyano group, facilitating the nucleophilic attack of methoxide
ion on carbon atom of cyano group and (2) as a transition metal
4.2.2. 1-Methoxy-3-(3-methylphenyl)benzo[b][1,6]naphthyridine
(3ab). White solid; isolated yield: 61.5 mg (82%); mp 111e112 ꢀC;
Rf¼0.28 (05:95 EtOAc/hexane); 1H NMR (300 MHz, CDCl3):
d 2.41 (s,
3H), 4.32 (s, 3H), 7.32 (d, J¼8.1 Hz,1H), 7.52e7.58 (m, 2H), 7.79e7.87
(m, 2H), 8.01 (d, J¼8.4 Hz, 2H), 8.14e8.20 (m, 3H), 9.15 (s, 1H); 13C
NMR (75 MHz, CDCl3):
d 21.6, 55.9, 120.1, 121.4, 126.4, 126.8, 127.9,
128.4, 128.7, 129.4, 129.7, 130.7, 132.2, 135.5, 137.9, 143.5, 148.9,
160.3; IR (KBr cmꢁ1): 2928, 3450. HRMS calcd for C20H17N2O
[MþH]þ 301.1341, found 301.1335.
catalyst, which forms complex B with
p-electrons of alkyne.
Complex B undergoes cyclization to give organopalladium in-
termediate C, which on protonation with AcOH gives cyclized
product 3a.
4.2.3. 1-Methoxy-3-(4-methylphenyl)-benzo[b][1,6]naphthyridine
(3ac). White solid; isolated yield: 61.5 mg 82%; mp 114e115 ꢀC;
3. Conclusions
Rf¼0.28 (05:95 EtOAc/hexane); 1H NMR (300 MHz, CDCl3):
d 2.43 (s,
3H), 4.32 (s, 3H), 7.32 (d, J¼7.5 Hz, 1H), 7.56 (d, J¼6.6 Hz, 1H), 7.85 (t,
In conclusion, we have developed a novel Pd-catalyzed one-pot
synthesis of benzo[b][1,6]naphthyridines and [1,6]naphthyridines
via CeC, CeN and CeO bonds formation from 2-chloroquinoline-3-
carbonitriles and 2-chloro-5-phenylpyrido-3-carbonitrile, re-
spectively. Further, the annulations are facile with the acetylene
bearing either alkyl group or phenyl ring with electron withdraw-
ing group. The reaction conditions avoided purification of in-
termediates, which saves time and solvents.
J¼8.1 Hz, 2H), 8.01 (d, J¼9.6 Hz, 2H), 8.14e8.20 (m, 3H), 9.15 (s, 1H);
13C NMR (75 MHz, CDCl3):
d 21.3, 54.2, 109.5, 113.9, 125.9, 126.4,
126.9, 128.5, 129.2, 129.4, 132.3, 132.6, 135.0, 135.8, 139.4, 142.5,
150.8, 161; IR (KBr cmꢁ1): 3437, 2924; HRMS calcd for C20H17N2O
[MþH]þ 301.1341, found 301.1335.
4.2.4. 1-Methoxy-3-(4-methoxyphenyl)benzo[b][1,6]naphthyridine
(3ad). Yellow solid; isolated yield: 67.0 mg (85%); mp 119e120 ꢀC;

9446
R.M. Singh et al. / Tetrahedron 69 (2013) 9443e9450
Table 2
Palladium-catalyzed one-pot synthesis of 1,3-disubstituted benzo[b][1,6]naphthyridinesa
Entry
Substrate
Intermediate
Sonogashira
coupling time (h)
Nucleo-/solvent
Product
Annulation
time (h)
Yieldb (%)
CN
Cl
CN
R
R
N
N
R'
(2)
(1)
OCH3
N
1
R¼H
3
MeOH
3
80
R' =
1a
N
3a
3ab
3ac
OCH3
N
2
3
4
5
R¼H
3.5
3.5
4
MeOH
MeOH
MeOH
MeOH
4
82
82
85
80
R' =
1a
N
OCH3
N
R¼H
4
R' =
N
1a
OCH3
N
R¼H
4
R' =
O
N
1a
O
3ad
OCH3
N
R¼H
2.5
2.5
R' =
F
N
1a
F
3ae
OCH3
N
H2
C
H2
C
6
7
R¼H
12
MeOH
MeOH
2
4
72c
CH3
R' =
C
C
C
1a
H2
H2
H2
N
3af
OCH3
CN
N
CN
3
76
N
N
N
Cl
R'
4
R' =
5a
OCH3
N
CN
Cl
8
9
4
MeOH
MeOH
5
2
80
76
R' =
O
N
N
4
O
5b
OCH3
N
CN
Cl
2.5
R' =
F
N
N
F
4
5c

R.M. Singh et al. / Tetrahedron 69 (2013) 9443e9450
9447
Table 2 (continued )
Entry
Substrate
Intermediate
Sonogashira
coupling time (h)
Nucleo-/solvent
Product
Annulation
time (h)
Yieldb (%)
CN
Cl
CN
R
R
N
N
R'
(2)
(1)
OCH3
N
10
11
12
R¼6-Me
3
MeOH
MeOH
MeOH
4
77
79
78
R' =
N
1b
3b
OCH3
N
O
R¼6-OMe
4
4.5
R' =
N
1c
3c
OCH3
N
R¼7-Me
4.5
4
R' =
1d
N
3d
OCH3
N
13
R¼7-OMe
5
MeOH
4
80
R' =
1e
O
N
3e
OCH3
N
14
15
16
R¼8-Me
5
3
3
MeOH
MeOH
MeOH
5
2
2
74
75
75
R' =
1f
N
3f
OCH3
N
R¼7-Cl
R' =
1g
Cl
N
3g
OCH3
N
Br
R¼6-Br
R' =
1h
N
3h
OC2H5
N
17
18
R¼H
3
3
EtOH
5
7
78
75
R' =
N
1a
3ag
OC4H9
N
R¼H
n-BuOH
1a
R' =
N
(continued on next page)
3ah

9448
R.M. Singh et al. / Tetrahedron 69 (2013) 9443e9450
Table 2 (continued )
Entry
Substrate
Intermediate
Sonogashira
coupling time (h)
Nucleo-/solvent
Product
Annulation
time (h)
Yieldb (%)
CN
Cl
CN
R
R
N
N
R'
(2)
(1)
19
20
R¼H
3
3
i-PrOH
t-BuOH
S.M.
S.M.
21
21
S.M.d
S.M.
R' =
1a
R¼H
R' =
R' =
1a
O
21
R¼H
3
12
72
N
HO
1a
N
Conditions:
a
(i) 5 mol % Pd(OAc)2, 10 mol % Ph3P, 2 equiv Et3N, CH3CN, 80 ꢀC, N2 atm; (ii) 5 mol % Pd(OAc)2, 10 mol % Ph3P, 1.5 equiv K2CO3, 4 mL MeOH, 80 ꢀC, air.
Isolated yields.
b
c
5 mol % Pd(OAc)2, 10 mol % Ph3P, 15 mol % CuI, 2 equiv Et3N, CH3CN, 80 ꢀC, N2 atmosphere for Sonogashira coupling and cyclization was performed on isolated product.
d
S.M.¼starting material.
160.9; IR (KBr cmꢁ1): 2925; HRMS calcd for C20H17N2O2 [MþH]þ
317.1290, found 317.1285.
4.2.5. 3-(4-Fluorophenyl)-1-methoxy-benzo[b][1,6]naphthyridine
(3ae). Yellow solid; isolated yield: 61.0 mg (80%); mp 118e119 ꢀC;
Rf¼0.25 (05:95 EtOAc/hexane); 1H NMR (300 MHz, CDCl3):
d 4.32 (s,
3H), 7.18 (d, J¼8.7 Hz, 1H), 7.58 (d, J¼8.1 Hz, 1H), 7.87 (t, J¼8.1 Hz,
1H), 7.98 (s, 1H), 8.04 (d, J¼8.1 Hz, 1H), 8.18e8.24 (m, 3H), 9.18 (s,
1H); 13C NMR (75 MHz, CDCl3):
d 54.3, 109.2, 109.5, 113.8, 115.5,
Fig. 2. ORTEP drawing of the X-ray structure of 3ac.
115.8, 126.1, 126.5, 128.2, 128.7, 128.8, 129.2, 132.8, 132.7, 135.3,
139.1, 161.1; IR (KBr cmꢁ1): 2961, 3056; HRMS calcd for C19H14FN2O
[MþH]þ 305.1090, found 305.1085.
N
C
4.2.6. 3-Hexyl-1-methoxy-benzo[b][1,6]naphthyridine (3af). Yellow
liquid; isolated yield: 53.0 mg (72%); Rf¼0.40 (05:95 EtOAc/hex-
OMe
N
N
Ph
2a
ane); 1H NMR (300 MHz, CDCl3):
d
0.89 (t, J¼6.3 Hz, 3H), 1.34e1.42
N
Ph
(m, 6H), 1.84 (t, 2H), 2.84 (t, J¼7.5 Hz, 2H), 4.20 (s, 3H), 7.34 (s, 1H),
7.52 (t, J¼7.2 Hz, 1H), 7.83 (t, J¼7.5 Hz, 1H), 8.01 (d, J¼8.1 Hz, 1H),
3a
Pd(OAc)2
8.16 (d, J¼8.7 Hz, 1H), 9.12 (s, 1H); 13C NMR (75 MHz, CDCl3):
d
14.0,
MeO
AcOH
22.6, 28.6, 28.9, 31.7, 38.2, 53.9, 112.3, 113.2, 125.3, 126.2, 128.9,
129.1, 131.8, 134.2, 151.1, 152.6, 157.0, 160.8; IR (KBr cmꢁ1): 2927;
HRMS calcd for C19H23N2O [MþH]þ 295.1810, found 295.1805.
N
C
OMe
N
Pd(OAc)2
N
Ph
A
N
Ph
Pd(OAc)
C
4.2.7. 5-Methoxy-3,7-diphenyl-[1,6]naphthyridine
(5a). White
solid; isolated yield: 59.2 mg (76%); mp 101e102 ꢀC; Rf¼0.30 (05:95
EtOAc/hexane); 101 ꢀC 1H NMR (300 MHz, CDCl3):
d 4.28 (s, 3H),
OMe
C
AcOH
NH
7.42e7.56 (m, 6H), 7.73 (d, J¼7.2 Hz, 2H), 7.98 (s, 1H), 8.22 (d,
J¼7.5 Hz, 2H), 8.68 (s, 1H), 9.27 (s, 1H); 13C NMR (75 MHz, CDCl3):
N
Ph
Pd(OAc)2
d 54.0, 111.3, 114.0, 126.8, 127.2, 128.2, 128.5, 128.6, 129.0, 129.2,
B
129.7, 134.1, 137.3, 138.7, 151.4, 153.7, 160.6; IR (KBr cmꢁ1): 2923;
HRMS calcd for C21H17N2O [MþH]þ 313.1341, found 313.1335.
Scheme 2. Plausible mechanism.
4.2.8. 5-Methoxy-7-(4-methoxy-phenyl)-3-phenyl[1,6]naphthyridine
(5b). White solid; isolated yield: 68.5 mg (80%); mp 129e130 ꢀC;
Rf¼0.15 (05:95 EtOAc/hexane); 1H NMR (300 MHz, CDCl3):
d
3.89 (s,
Rf¼0.30 (05:95 EtOAc/hexane); 1H NMR (300 MHz, CDCl3):
d 3.89 (s,
3H), 4.32 (s, 3H), 7.04 (d, J¼8.7 Hz, 2H), 7.54 (t, 1H), 7.85 (t, 1H), 7.95
3H), 4.26 (s, 3H), 7.03 (d, J¼9.0 Hz, 2H), 7.43e7.55 (m, 3H), 7.72 (d,
J¼7.5 Hz, 2H), 7.89 (s, 1H), 8.18 (d, J¼9.0 Hz, 2H), 8.66 (s, 1H), 9.25 (s,
(s, 1H), 8.03 (d, J¼8.4 Hz, 1H), 8.16e8.24 (m, 3H), 9.15 (s, 1H); 13C
NMR (75 MHz, CDCl3):
d
54.0, 55.3, 109.3, 113.6, 114.0, 125.5, 126.3,
1H); 13C NMR (75 MHz, CDCl3):
d 53.8, 55.2, 110.0, 113.6, 114.0, 127.1,
128.2, 128.9, 129.2, 131.3, 132.0, 134.2, 150.8, 151.4, 152.9, 160.5,
127.2, 128.1, 129.1, 129.6, 131.3, 133.4, 133.7, 137.4, 151.2, 152.8, 153.6,

R.M. Singh et al. / Tetrahedron 69 (2013) 9443e9450
9449
160.5; IR (KBr cmꢁ1): 2925; HRMS calcd for C22H19N2O2 [MþH]þ
3H), 7.42e7.54 (m, 2H), 7.69 (d, J¼8.4 Hz, 1H), 7.88 (d, J¼8.4 Hz, 1H),
7.96e8.32 (m, 3H), 8.37 (s, 1H), 9.15 (s, 1H); 13C NMR (75 MHz,
343.1447, found 343.1420.
CDCl3):
d 54.6, 110.6, 120.5, 121.5, 126.5, 126.9, 127.2, 127.7, 128.5,
4.2.9. 7-(4-Fluoro-phenyl)-5-methoxy-3-phenyl-[1,6]naphthyridine
128.7, 129.0, 130.4, 131.6, 134.4, 144.8, 148.0, 160.4; IR (KBr cmꢁ1):
2925; HRMS calcd for C19H14ClN2O [MþH]þ 321.0795, found
321.0789.
(5c). White solid; isolated yield: 62.7 mg (76%); mp 121e122 ꢀC;
Rf¼0.40 (05:95 EtOAc/hexane); 1H NMR (300 MHz, CDCl3):
d 4.27 (s,
3H), 7.19 (d, J¼8.7 Hz, 1H), 7.51e7.58 (m, 4H), 7.73 (d, J¼7.2 Hz, 2H),
7.91 (s, 1H), 8.19 (d, J¼8.1 Hz, 2H), 8.68 (s, 1H), 9.26 (s, 1H); 13C NMR
4.2.16. 8-Bromo-1-methoxy-3-phenyl-benzo[b][1,6]naphthyridine
(3h). Yellow solid; isolated yield: 68.0 mg (75%); mp 92e93 ꢀC;
(75 MHz, CDCl3):
d
54.09, 111.01, 113.98, 115.74, 127.24, 128.64,
129.23, 129.74, 134.23, 137.30, 150.41, 151.30, 152.73, 153.80, 160.68,
161.85, 165.74; IR (KBr cmꢁ1): 2923; HRMS calcd for C21H16FN2O
[MþH]þ 331.1247, found 331.1221.
Rf¼0.22 (05:95 EtOAc/hexane); 1H NMR (300 MHz, CDCl3):
d 4.33 (s,
3H), 7.43e7.58 (m, 4H), 7.86 (t, J¼7.8 Hz, 1H), 8.03 (d, J¼8.4 Hz, 2H),
8.20 (d, J¼8.7 Hz, 1H), 8.26 (d, J¼7.5 Hz, 2H), 9.17 (s, 1H); 13C NMR
(75 MHz, CDCl3): d 54.1, 110.8, 113.9, 125.8, 126.8, 128.5, 128.7, 129.1,
4.2.10. 1-Methoxy-8-methyl-3-phenyl-benzo[b][1,6]naphthyridine
129.2, 132.2, 132.6, 134.4, 138.7, 142.0, 142.4, 152.7, 161.1; IR (KBr
cmꢁ1): 2924. HRMS calcd for C19H14BrN2O [MþH]þ 365.0289,
found 365.0263.
(3b). Yellow solid; isolated yield: 57.7 mg (77%); mp 95e96 ꢀC;
Rf¼0.30 (05:95 EtOAc/hexane); 1H NMR (300 MHz, CDCl3):
d 2.59 (s,
3H), 4.32 (s, 3H), 7.43 (d, J¼6.9 Hz, 1H), 7.48e7.56 (m, 2H), 7.69 (d,
J¼8.7 Hz, 1H), 7.77 (s, 1H), 8.03e8.11 (m, 2H), 8.26 (d, J¼7.2 Hz, 2H),
4.2.17. 1-Ethoxy-3-phenyl-benzo[b][1,6]naphthyridine (3ag). Yellow
solid; isolated yield: 58.5 mg (78%); mp 90e91 ꢀC; Rf¼0.33 (05:95
9.05 (s, 1H); 13C NMR (75 MHz, CDCl3):
d 21.7, 54.1, 110.7, 114.0,
126.8, 127.3, 128.6, 129.8, 132.3, 133.2, 135.1, 135.7, 138.8, 145.6,
146.0, 148.0, 160.3, 164.0; IR (KBr cmꢁ1): 2924; HRMS calcd for
C20H17N2O [MþH]þ 301.1341, found 301.1335.
EtOAc/hexane); 1H NMR (300 MHz, CDCl3):
d
1.62 (t, J¼6.9 Hz, 3H),
4.81 (q, 2H), 7.40e7.58 (m, 4H), 7.85 (t, J¼7.5 Hz, 1H), 8.05 (d,
J¼7.8 Hz, 2H), 8.18e8.26 (m, 3H), 9.18 (s, 1H); 13C NMR (75 MHz,
CDCl3):
d
¼14.5, 62.6, 110.5, 114.3, 125.7, 126.5, 126.8, 128.4, 128.6,
4.2.11. 1,8-Dimethoxy-3-phenyl-benzo[b][1,6]naphthyridine
129.0, 129.1, 132.0, 134.2, 138.8, 151.1, 151.4, 152.8, 160.7; IR (KBr
cmꢁ1): 2926, 3432; HRMS calcd for C20H17N2O [MþH]þ 301.1341,
found 301.1322.
(3c). Yellow solid; isolated yield: 62.50 mg (79%); mp 108e109 ꢀC;
Rf¼0.28 (05:95 EtOAc/hexane); 1H NMR (300 MHz, CDCl3):
d 3.98 (s,
3H), 4.32 (s, 3H), 7.41 (d, J¼6.9 Hz, 1H), 7.48e7.56 (m, 3H), 8.02 (s,
1H), 8.08 (d, J¼9.6 Hz, 1H), 8.25 (d, J¼7.5 Hz, 3H), 9.02 (s, 1H); 13C
4.2.18. 1-Butoxy-3-phenyl-benzo[b][1,6]naphthyridine
NMR (75 MHz, CDCl3):
d
54.0, 55.5, 104.4, 110.8, 114.0, 126.7, 126.9,
(3ah). Yellow solid; isolated yield: 61.5 mg (75%); mp 74e75 ꢀC;
127.5, 128.6, 128.8, 130.4, 131.7, 138.8, 148.4, 149.8, 151.1, 157.1, 160.6;
IR (KBr cmꢁ1): 2924; HRMS calcd for C20H17N2O2 [MþH]þ 317.1290,
found 317.1285.
Rf¼0.30 (05:95 EtOAc/hexane); 1H NMR (300 MHz, CDCl3):
d 1.08 (t,
J¼7.5 Hz, 3H), 1.53e1.69 (m, 2H), 2.00 (t, J¼7.8 Hz, 2H), 4.75 (t,
J¼6.3 Hz, 2H), 7.42e7.58 (m, 4H), 7.85 (t, J¼7.8 Hz, 1H), 8.03 (d,
J¼9.6 Hz, 2H), 8.18e8.26 (m, 3H), 9.16 (s, 1H); 13C NMR (75 MHz,
4.2.12. 1-Methoxy-7-methyl-3-phenyl-benzo[b][1,6]naphthyridine
(3d). Light yellow solid; isolated yield: 58.5 mg (78%);
mp 98e99 ꢀC; Rf¼0.30 (05:95 EtOAc/hexane); 1H NMR (300 MHz,
CDCl3): d 13.9, 19.5, 31.0, 66.6, 110.6, 114.1, 125.7, 126.5, 126.8, 128.3,
128.6, 129.0, 129.1, 132.0, 134.2, 138.8, 151.1, 151.4, 152.8, 160.9; IR
(KBr cmꢁ1): 2927; HRMS calcd for C22H21N2O [MþH]þ 329.1654,
found 329.1648.
CDCl3):
d 2.66 (s, 3H), 4.32 (s, 3H), 7.38e7.45 (m, 2H), 7.51 (t,
J¼7.5 Hz, 2H), 7.92 (m, 2H), 8.02 (s, 1H), 8.26 (d, J¼7.5 Hz, 2H), 9.11
(s, 1H); 13C NMR (75 MHz, CDCl3):
d
22.5, 54.2, 106.4, 127.0, 127.3,
4.2.19. 1-Phenoxy-3-phenyl-benzo[b][1,6]naphthyridine
127.5, 127.8, 128.1, 128.5, 128.7, 128.9, 129.1, 129.3, 129.7, 142.0,
143.5, 154.5, 162.8; IR (KBr cmꢁ1): 2924; HRMS calcd for C20H17N2O
[MþH]þ 301.1341, found 301.1335.
(4ai). Yellow liquid; isolated yield: 62.5 mg (72%); Rf¼0.10 (05:95
EtOAc/hexane); 1H NMR (300 MHz, CDCl3):
d
6.84 (t, J¼8.7 Hz, 1H),
6.94 (t, J¼7.2 Hz, 1H), 7.41e7.52 (m, 6H), 7.83 (t, J¼8.1 Hz, 1H), 7.97
(t, J¼7.8 Hz, 3H), 8.15 (d, J¼8.7 Hz, 1H), 8.25 (d, J¼6.9 Hz, 2H), 9.00
4.2.13. 1,7-Dimethoxy-3-phenyl-benzo[b][1,6]naphthyridine(3e). -
Light green solid; isolated yield: 63.5 mg (80%); mp 115e116 ꢀC;
(s, 1H); 13C NMR (75 MHz, CDCl3):
d 109.3, 114.5, 125.4, 125.5, 126.4,
126.9, 128.5, 128.6, 128.9, 129.0, 129.5, 136.0, 139.2, 150.6, 151.5,
153.7, 154.4, 161.4; IR (KBr cmꢁ1): 2927; HRMS calcd for C24H17N2O
[MþH]þ 349.1341, found 349.1335.
Rf¼0.28 (05:95 EtOAc/hexane); 1H NMR (300 MHz, CDCl3):
d 3.98 (s,
3H), 4.32 (s, 3H), 7.41e7.55 (m, 5H), 8.02 (s, 1H), 8.07 (d, J¼9.6 Hz,
1H), 8.24 (d, J¼7.5 Hz, 2H), 9.02 (s, 1H); 13C NMR (75 MHz, CDCl3):
d
54.0, 55.5, 104.3, 110.8, 113.9, 126.6, 126.9, 127.4, 128.6, 128.8,
Acknowledgements
130.4, 131.7, 138.8, 148.3, 149.8, 151.0, 157.0, 160.5; IR (KBr cmꢁ1):
2925; HRMS calcd for C20H17N2O2 [MþH]þ 317.1290, found
317.1278.
We are thankful to UGC, New Delhi for fellowships to R.K., N.S.
(SRF), M.A. (RFSMS). We are also thankful to Prof. V. K. Singh, Di-
rector, IISER Bhopal, India and Dr. G. Pandey, Director, CBMR,
Lucknow, India for providing HRMS data. Dr. Suryabhan Singh,
Banaras Hindu University for his kind help in solving X-ray crys-
tallographic data.
4.2.14. 1-Methoxy-6-methyl-3-phenyl-benzo[b][1,6]naphthyridine
(3f). Light yellow solid; isolated yield: 55.5 mg 74%;
mp 123e124 ꢀC; Rf¼0.40 (05:95 EtOAc/hexane); 1H NMR (300 MHz,
CDCl3): d 2.93 (s, 3H), 4.33 (s, 3H), 7.42e7.51 (m, 3H), 7.57e7.68 (m,
2H), 7.77e7.89 (m, 1H), 8.10 (s, 1H), 8.26e8.30 (m, 2H), 9.12 (s, 1H);
References and notes
13C NMR (75 MHz, CDCl3):
d
18.3, 54.0, 111.4, 119.3, 125.5, 126.8,
1. (a) Larghi, E. L.; Obrist, B. V.; Kaufman, T. S. Tetrahedron 2008, 64, 5236; (b)
Larghi, E. L.; Bohn, M. L.; Kaufman, T. S. Tetrahedron 2009, 65, 4257; (c) Taka-
hashi, Y.; Kubota, T.; Shibazaki, A.; Gonoi, T.; Fromont, J.; Kobayashi, J. Org. Lett.
2011, 13, 3016; (d) Caixia, L.; Xuli, T.; Pinglin, L.; Guoqiang, L. Org. Lett. 2012, 14,
1994.
127.1, 127.8, 128.6, 128.8, 131.4, 132.9, 134.0, 138.8, 142.7, 145.4,
152.0, 160.9; IR (KBr cmꢁ1): 2919; HRMS calcd for C20H17N2O
[MþH]þ 301.1341, found 301.1335.
2. (a) Tsuzuki, Y.; Tomita, K.; Sato, Y.; Kashimoto, S.; Chiba, K. Bioorg. Med. Chem.
Lett. 2004, 14, 3189; (b) Srivastava, S. K.; Jaggi, M.; Singh, A. T.; Madan, A.; Rani,
N.; Vishnoi, M.; Agarwal, S. K.; Mukherjee, R.; Burman, A. C. Bioorg. Med. Chem.
Lett. 2007, 17, 6660.
4.2.15. 7-Chloro-1-methoxy-3-phenyl-benzo[b][1,6]naphthyridine
(3g). Green solid; isolated yield: 60.0 mg (75%); mp 79e80 ꢀC;
Rf¼0.25 (05:95 EtOAc/hexane); 1H NMR (300 MHz, CDCl3):
d 4.33 (s,

9450
R.M. Singh et al. / Tetrahedron 69 (2013) 9443e9450
3. (a) Zhuang, L.; Wai, S. J.; Embrey, M. W.; Fisher, T. E.; Egbertson, M. S.; Payne, L.
S.; Guare, J. P., Jr.; Vacca, J. P.; Hazuda, D. J.; Felock, P. J.; Wolfe, A. L.; Stillmock,
K. A.; Witmer, M. V.; Moyer, G.; Schleif, W. A.; Gabryelski, L. J.; Leonard, Y. M.;
Lynch, J. J.; Michelson, S. R.; Young, S. D. J. Med. Chem. 2003, 46, 453; (b) Embrey,
M. W.; Wai, J. S.; Funk, T. W.; Homnick, C. F.; Perlow, D. S.; Young, S. D.; Vacca, J.
P.; Hazuda, D. J.; Felock, P. J.; Stillmock, K. A.; Witmer, M. V.; Moyer, G.; Schleif,
W. A.; Gabryelski, L. J.; Jin, L.; Chen, I. W.; Ellis, J. D.; Wong, B. K.; Lin, J. H.;
Leonard, Y. M.; Tsou, N. N.; Zhuang, L. Bioorg. Med. Chem. Lett. 2005, 15, 4550; (c)
Johns, B. A.; Weatherhead, J. G.; Allen, S. H.; Thompson, J. B.; Garvey, E. P.;
Foster, S. A.; Jeffrey, J. L.; Miller, W. H. Bioorg. Med. Chem. Lett. 2009, 19, 1802.
4. Li, Y.; Liang, J.; Siu, T.; Hu, E.; Rossi, M. A.; Barnett, S. F.; Defoe-Jones, D.; Jones,
R. E.; Robinson, R. G.; Leander, K.; Huber, H. E.; Mittal, S.; Cosford, N.; Prasit, P.
Bioorg. Med. Chem. Lett. 2009, 19, 834.
5. Deady, L. W.; Rogers, M. L.; Zhuang, L.; Baguley, B. C.; Denny, W. A. Bioorg. Med.
Chem. 2005, 13, 1341.
6. (a) Deady, L. W.; Rodemann, T.; Zhuang, L.; Baguley, B. C.; Denny, W. A. J. Med.
Chem. 2003, 46, 1049; (b) Suresh, T.; Dhanabal, T.; Kumar, R. N.; Mohan, P. S.
Indian J. Chem., Sect. B 2005, 44, 2375; (c) Mukhopadhyay, C.; Das, P.; Butcher, R.
J. Org. Lett. 2011, 13, 4664.
C.; Burch, J. D. Org. Lett. 2008, 10, 4211; (j) Wang, J. R.; Manabe, K. J. Org. Chem.
2010, 75, 5340; (k) Fernandes, T. A.; Vaz, B. G.; Eberlin, M. N.; Silva, A. J. M.;
Costa, P. R. R. J. Org. Chem. 2010, 75, 7085; (l) Maimone, T. J.; Buchwald, S. L. J.
Am. Chem. Soc. 2010, 132, 9990; (m) Wang, S.; Li, P.; Yu, L.; Wang, L. Org. Lett.
2011, 13, 5968; (n) Ward, A. F.; Xu, Y.; Wolfe, J. P. Chem. Commun. 2012, 609; (o)
Li, Y.; Qi, Z.; Wang, H.; Fu, X.; Duan, C. J. Org. Chem. 2012, 77, 2053.
12. (a) Zhang, H.; Larock, R. C. Org. Lett. 2001, 3, 3083; (b) Roesch, K. R.; Zhang, H.;
Larock, R. C. J. Org. Chem. 2001, 66, 8042; (c) Roesch, K. R.; Larock, R. C. J. Org.
Chem. 2002, 67, 86; (d) Zhang, H.; Larock, R. C. J. Org. Chem. 2002, 67, 9318; (e)
Zhang, H.; Larock, R. C. Tetrahedron Lett. 2002, 43, 1359; (f) Huang, Q.; Larock, R.
C. Tetrahedron Lett. 2002, 43, 3557; (g) Gabriele, B.; Veltri, L.; Maltese, V.; Spina,
R.; Mancuso, R.; Salerno, G. Eur. J. Org. Chem. 2011, 5626.
13. Larock, R. C.; Tian, Q.; Pletnev, A. A. J. Am. Chem. Soc. 1999, 121, 3238.
14. Wei, L. M.; Lin, C. F.; Wu, M. J. Tetrahedron Lett. 2000, 41, 1215.
15. (a) Singh, R. M.; Chandra, A.; Sharma, N.; Singh, B.; Kumar, R. Tetrahedron 2012,
68, 9206; (b) Chandra, A.; Singh, B.; Khanna, R. S.; Singh, R. M. J. Org. Chem.
2009, 74, 5664.
16. Crystal data for 3ac: empirical formula, C20H16N2O; formula weight, 300.
35; crystal colour, habit: light yellow, block; crystal system, triclinic; lattice
7. (a) Larock, R. C.; Kuo, M. Y. Tetrahedron Lett. 1991, 32, 569; (b) Phuan, P. W.;
parameters, a¼8.9724(12), b¼9.7978(14), c¼10.2831(13),
a
¼89.148ꢀ (11),
Kozlowski, M. C. Tetrahedron Lett. 2001, 42, 3963.
8. Rudys, S.; Rios-Luci, C.; Perez-Roth, E.; Cikotiene, I.; Padron, J. M. Bioorg. Med.
b
¼67.507ꢀ (13),
g
¼68.453ꢀ (13), space group Pꢁ1; Z¼2; Dcalcd¼1.293 g/cm3;
ꢀ
R
(int.)¼0.0178; reflections collected/unique 5525/4109; refinement
Chem. Lett. 2010, 20, 1504.
9. Numata, A.; Kondo, Y.; Sakamoto, T. Synthesis 1999, 306.
method full-matrix least-squares on F2; melting point 114e115 ꢀC; R in-
dices (index ranges) ꢁ11ꢂhꢂ11, ꢁ12ꢂkꢂ13, ꢁ12ꢂlꢂ12; GoF 1.024; R1 0.
10. Chandra, A.; Singh, B.; Upadhyay, S.; Singh, R. M. Tetrahedron 2008, 64, 11680.
11. (a) Spencer, J.; Pfeffer, M. J. Org. Chem. 1995, 60, 1005; (b) Larock, R. C.; Wei, L.;
Hightower, T. R. Synlett 1998, 522; (c) Kadnikov, D. V.; Larock, R. C. Org. Lett.
2000, 2, 3643; (d) Asao, N.; Nogami, T.; Takahashi, K.; Yamamoto, Y. J. Am. Chem.
Soc. 2002, 124, 764; (e) Kamino, T.; Kuramochi, K.; Kobayashi, S. Tetrahedron Lett.
2003, 44, 7349; (f) Trost, B. M.; Toste, F. D.; Greenman, K. J. Am. Chem. Soc. 2003,
125, 4518; (g) Nakamura, I.; Yamamoto, Y. Chem. Rev. 2004, 104, 2127; (h)
Alonso, F.; Beletskaya, I. P.; Yus, M. Chem. Rev. 2004, 104, 3079; (i) Eidamshaus,
0649; wR2 0.1896; largest diff. peak and hole (e Aꢁ3
)
0.27 and ꢁ0.22.
Crystallographic data (excluding structure factors) for the structures in this
Letter have been deposited with the Cambridge Crystallographic Data
Centre as supplementary publication number CCDC 908156. Copies of the
data can be obtained free of charge on an application to CCDC, 12 Union
Road, Cambridge CB2 1EZ, UK [fax: þ44 1223336033 or e-mail: deposit@
ccdc.cam.ac.uk].
17. Upadhyay, S.; Chandra, A.; Singh, R. M. Indian J. Chem., Sect. B 2009, 48, 152.