A general and efficient method for the synthesis of benzo-(iso)quinoline derivatives

Article abstract of DOI:10.1016/j.tet.2008.09.015

A new, short and efficient synthesis of substituted benzo-(iso)quinoline derivatives is reported. The methodology is based on a Suzuki or Negishi cross-coupling followed by a cyclization reaction induced by t-BuOK in DMF to form the central ring. This approach allowed the synthesis of all four benzo-(iso)quinoline isomers and the substitution of each ring of the benzo-(iso)quinoline core.

Full text of DOI:10.1016/j.tet.2008.09.015

Tetrahedron 64 (2008) 10699–10705
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
A general and efficient method for the synthesis of benzo-(iso)quinoline
derivatives
*
´ ´
¨
Victor Mamane , Frederic Louerat, Julien Iehl, Mohamed Abboud, Yves Fort
Equipe Synthe`se Organome´tallique et R´eactivite´ (SOR), Laboratoire SRSMC, UMR CNRS-UHP 7565, Nancy Universite´, BP 239, Bd des Aiguillettes, 54506 Vandoeuvre-les-Nancy, France
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 10 July 2008
Received in revised form 28 August 2008
Accepted 1 September 2008
Available online 17 September 2008
A new, short and efficient synthesis of substituted benzo-(iso)quinoline derivatives is reported. The
methodology is based on a Suzuki or Negishi cross-coupling followed by a cyclization reaction induced
by t-BuOK in DMF to form the central ring. This approach allowed the synthesis of all four benzo-
(iso)quinoline isomers and the substitution of each ring of the benzo-(iso)quinoline core.
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
ring. This convergent strategy facilitates the introduction of sub-
stituents on each cycle of the benzoquinoline core including the
Benzoquinoline derivatives are very useful compounds in vari-
ous fields of chemistry, including biological and pharmacological
chemistry.1 Moreover, some derivatives exhibit very interesting
photophysical properties2 and a recent work showed their utility as
ligands for the preparation of helical complexes.3
central ring due to the facile deprotonation of the methyl group of
picolines (Fig. 1).12
The base-promoted cyclization step has been previously used in
the benzene series by de Koning and co-workers.13 They found that
t-BuOK in DMF at 80 ꢀC in presence of light could allow the intra-
molecular condensation between a methyl group attached to
a benzene ring and an aldehyde. The same base was used with
success in our work and we noted that irradiation and heating were
not necessary due to the higher reactivity of the methyl group in
picolines.
In view of the importance of benzoquinoline derivatives, several
methods have been developed for their synthesis. Most of them are
based on the construction of the pyridine ring implying starting
from substituted naphthalenes, which are not always easily avala-
ible.4 An alternative approach starting from a quinoline derivative
was also proposed by using a Diels–Alder reaction.5 In contrast,
methods based on the construction of the central ring are quite
limited. This approach allowed an efficient synthesis of toddaqui-
noline by an intramolecular radical cyclization.6 Analogously to the
phenanthrene synthesis, benzoquinoline derivatives were pro-
duced efficiently through a photocyclization–oxidation process.7
Both methods were recently used to prepare monoazahelicenes.8
As model reaction products of azacorannulenes, benzoquinolines
2. Results and discussion
Our initial efforts were focused on the synthesis of benzo-
(iso)quinoline derivatives possessing an unsubstituted central ring.
Among the palladium-catalyzed cross-coupling methods available
to generate the aryl–heteroaryl bond, the Suzuki reaction14 was
were obtained by flash vacuum pyrolysis of ethynylpyridines.9
A
nice entry to benzoquinolines and other aza-polycyclic aromatic
compounds was recently described via superelectrophilic
cyclizations.10
Herein we described a general method to synthesize all four
benzo-(iso)quinoline isomers. Our approach, which has proven to
be efficient for the preparation of ferroceno-(iso)quinolines11 in-
volves a two-step process including: (i) a palladium-catalyzed
cross-coupling reaction to bring together the pyridine and the aryl
moieties and (ii) a base-promoted cyclization to build the central
Me
R1
R1
B(OH)2
CHO
R2
CHO
R2
N
N
R2
R1
Me
Br
N
R3
R1
R1
O
Me
ZnCl
R2
N
O
N
O
O
R2
R2
* Corresponding author. Tel.: þ33 3 83 68 47 84; fax: þ33 3 83 68 47 85.
E-mail address: victor.mamane@sor.uhp-nancy.fr (V. Mamane).
Figure 1. General approach to substituted benzo-(iso)quinolines.
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.09.015

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V. Mamane et al. / Tetrahedron 64 (2008) 10699–10705
Table 1
Scope of the two-step sequence leading to the benzo-(iso)quinoline derivatives
Entry
1
Pyridines 1
Boronic acids 2
Coupling products 3a
Cyclization products 4b
Yield of 3 (%)
Yield of 4 (%)
CHO
OTf
80
75
(HO)2B
N
CHO
N
3a
1a
N
2a
4a
2
3
4
5
6
2a
94
90
78
60
51
44
42
Br
N
N
CHO
N
1b
3b
4b
2a
2a
2a
2a
Br
N
CHO
CHO
N
N
4c
1c
3c
3d
3e
93
Br
N
1d
N
N
4d
53c
Br
Br
Br
Br
CHO
N
1e
N
N
4e
42
Br
CHO
Me2N
N
Me2N
N
Me2N
N
1f
3f
4f
O
O
7
1a
72d
65
O
CHO
O
O
O
O
O
(HO)2B
O
CHO
O
N
N
4g
2b
3g
8
1b
2b
98d
88
CHO
N
N
3h
4h
9e
2a
d
43
N
N
1g
Br
O
5
a
General conditions: 1 (1 mmol), 2 (1.1 mmol, 1 M in MeOH), 5 mol % Pd(PPh3)4, Na2CO3 (2 mmol, 1 M in H2O), toluene, 90 ꢀC.
General conditions: 3 (0.5 mmol, 1 M in DMF), t-BuOK (1 mmol, 1 M in DMF), rt.
Compound 2a (2.2 equiv) was used.
Boronic acid (1.5 equiv) was used.
Compound 5 was formed during the Suzuki reaction.
b
c
d
e

V. Mamane et al. / Tetrahedron 64 (2008) 10699–10705
10701
chosen for its high efficiency and because aldehyde protection was
not necessary. Standard conditions (5 mol % Pd(PPh3)4, 1 M Na2CO3,
toluene/methanol, 90 ꢀC) were used in all cases and no optimization
of the catalyst was necessary. For the cyclization step, a two-fold
excess of t-BuOK in DMF was used to achieve complete conversions.
The scope of this two-step methodology is presented in Table 1.
The Suzuki protocol was very efficient for coupling picolines 1a–
c15 with boronic acid 2a thus producing aldehydes 3a–c, which
upon treatment with t-BuOK delivered the desired benzo[f]quino-
line 4a, benzo[h]isoquinoline 4b, and benzo[f]isoquinoline 4c
(entries 1–3). This two-step sequence allowed a rapid access to
several substituted benzo-(iso)quinoline derivatives only by
adjusting the two reaction components, i.e., the boronic acid and
the pyridine ring. Easily available polysubstituted bromopyridines
1d–f16 have been successfully used in this sequence with boronic
acid 2a to generate highly substituted benzo[h]isoquinolines 4d–f
(entries 4–6). In the first step, 1,10,2-trisubstituted biaryl systems
were produced with moderate to good yields using standard con-
ditions. Note that the double Suzuki coupling with substrate 1e did
not work and only the mono-coupling product 3e was formed. In
the second step we observed that the cyclization reaction occurred
selectively with the methyl group para to the nitrogen.17 Although
the yields are moderate, the syntheses remain very attractive for
these three compounds because they bear several functional
groups as the methyl group,18 the bromine atom or the dimethyl-
amino group. The substitution of the external aromatic ring was
obtained by employing boronic acid 2b. Benzo-(iso)quinoline de-
rivatives 4g and 4h were formed with good to excellent yields
(entries 7 and 8). With picoline 1g, the expected aldehyde was not
observed and instead the cyclized product 5 was produced through
a cascade process (entry 9).19
1) t-BuLi
Br
O
N
2) ZnCl2
N
O
p-TSA
O
-O
3) 1g, Pdcat
H
65%
8
O
6
7
NaHCO3
37%
1) t-BuLi; 2) ZnCl2
3) Pdcat
50%
overall
,
5
Cl
N
9
Br
Cl
N
t-BuOK
DMF
67%
p-TSA
81%
Cl
N
O
Cl
N
OHC
11
O
10
12
Scheme 1. Synthesis of 2-chlorobenzo[h]quinoline 12.
The presence of a chlorine in 2-position of compound 12 allows
a range of functional groups to be incorporated. It was already
shown that piperidine or piperazine derivatives can be used to
displace the chlorine atom by nucleophilic substitution.1e,f,23 We
then wanted to expand the potential synthetic utility of benzo-
quinoline 12 by introducing aromatic rings in 2-position. The
Suzuki cross-coupling of 12 with different arylboronic acids fur-
nished 2-arylbenzo[h]quinolines 13–15 with good yields. It is in-
teresting to note that compound 14 did not cyclize during the
Suzuki reaction in contrast to 2-chloroquinoline19a showing again
the extreme sensitivity of this reaction to structural changes
(Scheme 2).
It is noteworthy that our method presents only one limitation
because benzo[h]quinoline derivatives are not accessible due to
a parasite reaction between pyridine 1g and boronic acid 2a. To
avoid the intramolecular attack of the aldehyde by the pyridine
nitrogen, we decided to protect the aldehyde function and in that
case we found more convenient to use the Negishi reaction20 to
perform the cross-coupling. This strategy was proven successful in
the case of ferrocenyl analogues since the aldehyde intermediate
could be isolated to give ferroceno[h]quinoline after a t-BuOK-
promoted cyclization (Fig. 2).11
The same methodology applied to bromoacetal 6 furnished the
cross-coupling product 7, which upon treatment with p-TSA did not
yield the desired compound aldehyde. Quenching the reaction
mixture with NaHCO3 furnished again derivative 5 with 37% yield.
When the mixture was treated with pH7 buffer, 1H and 13C NMR
analyses showed that no aldehyde nor cyclization product was
formed but probably the cyclized product 8 as previously proposed
by Igeta and co-workers.21 It seems that this reaction is very sen-
sitive to structural changes22 and we anticipated that introducing
an electron-withdrawing substituent ortho to the nitrogen could
lower its nucleophilicity. Thus, repeating the Negishi coupling with
pyridine 911 bearing a chlorine in 2-position delivered acetal 10 and
after hydrolysis in presence of p-TSA we could isolate aldehyde 11 in
good yield. Finally, treating 11 with 2 equiv of t-BuOK in DMF fur-
nished 2-chlorobenzo[h]quinoline 12 (Scheme 1).
Ar
1.5 equiv. ArB(OH)2
5% Pd(PPh3)4
Ar
13 (67%)
N
2 equiv. NaHCO3
CHO
12
Toluene, MeOH, H2O
90 °C, 12h
14 (76%)
15 (79%)
MeS
Scheme 2. Preparation of 2-arylbenzo[h]quinoline derivative.
Finally, we turned our attention to the elaboration of the central
ring of benzo-(iso)quinolines (Scheme 3). Acetals 16a,b were
obtained by protecting aldehydes 3a,b in benzene. This solvent was
preferred to toluene because we observed partial acid-promoted
cyclization of 3a to 4a caused by the use of a more elevated tem-
perature during the azeotropic distillation. Alternatively, these
compounds could be obtained directly from 6 by using a Negishi
cross-coupling reaction. Starting from 16a,b we developed a ‘one-
pot’ procedure to access directly benzo-(iso)quinoline derivatives
17 and 18 bearing an electron-withdrawing group on the central
ring.24 We found that the methyl functionalization step was very
substrate- and electrophile-dependant. Acetal 16a could be
deprotonated on the methyl group by n-BuLi but the lithiated in-
termediate reacted with DMA (dimethylacetamide) while being
unreactive with dimethylcarbonate. In this last case, prior metal-
ation with NDA (sodium diisopropylamide) was necessary to ach-
ieve good conversion.15a,18 When using acetal 16b, n-BuLi was not
effective even with DMA as the electrophile and again NDA was
necessary to give good conversions. It is worth noting that with
NDA as the base, DMA did not react and the use of EtOAc was
necessary in that case. After the end of the metalation-electrophilic
O
O
1g
O
ZnCl
Pdcat
N
t-BuOK
DMF
Fe
Fe
N
Fe
then
p-TSA
Figure 2. Synthesis of ferroceno[h]quinoline through Negishi coupling.

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V. Mamane et al. / Tetrahedron 64 (2008) 10699–10705
Acetal
Base
EX
APTS
Product
Yield
(%)
(n equiv.)
(n equiv.)
O
1) Base
2) EX
Ethylene glycol
Benzene
DMA
16a
16a
16b
16b
n-BuLi (2)
NDA (3.5)
NDA (3.5)
NDA (3.5)
10
20
20
20
17a
18a
17b
55
73
44
40
O
N
3) APTS
p-TSAcat
(MeO)2CO
EtOAc
3a,b
N
3a : 83%
3b : 86%
"one-pot"
E
a
16a,b
17,18
(MeO)2CO
18b
a A transesterification step (K2CO3, EtOH) was necessary to separate the product
from the starting aldehyde 3b
1) t-BuLi
2) ZnCl2
3) 1a or 1b, Pdcat
R = Me 17b
R = OEt 18b
N
R = Me 17a
R = OMe 18a
6
1a : 67%
1b : 68%
N
COR
COR
Scheme 3. Fonctionnalization of the central ring of benzo-(iso)quinolines.
trapping step, excess p-TSA was added causing deprotection of the
aldehyde and subsequent cyclization to give compounds 17b and
18a,b with moderate to good yields.
reaction mixture was cooled to room temperature, extracted with
ethyl acetate (30 mL) and dried over MgSO4. After concentration,
the residue was purified by chromatography (hexanes/ethyl ace-
tate/triethylamine 8:1:1) to give compound 3b as a yellow solid
3. Summary
(930 mg, 94%). Mp: 77 ꢀC; 1H NMR (200 MHz, CDCl3)
d 9.78 (s, 1H),
8.54 (d, J¼5 Hz, 1H), 8.42 (s, 1H), 8.06 (d, J¼8.2 Hz, 1H), 7.70 (t,
We have developed a short and efficient synthesis of substituted
benzo-(iso)quinolines. Our approach based on the construction of
the central ring by a base-promoted cyclization allowed the in-
troduction of substituents on each cycle of the benzo-(iso)quinoline
core. All four isomers depending on the nitrogen position on the
pyridine ring were accessible by this methodology, which make it
very attractive for biological studies.
J¼7.4 Hz, 1H), 7.58 (t, J¼7.4 Hz, 1H), 7.31 (d, J¼7.6 Hz, 1H), 7.26 (d,
J¼5 Hz, 1H), 2.14 (s, 3H); 13C NMR (50 MHz, CDCl3)
d 191.0, 149.5,
149.1, 145.4, 140.8, 133.9, 133.8, 130.9, 128.5, 128.1, 124.7, 19.6. MS
(EI) m/z 197 (Mþ, 95%), 196 ([Mꢁ1]þ, 100), 182 (40), 168 (39), 167
(42), 115 (29). HRMS m/z calcd for C13H11NO: 197.0841, found:
198.0913 (MHþ).
4.2.2. 2-(2-Methyl-pyridin-3-yl)-benzaldehyde (3a)
4. Experimental part
4.1. General
Yellow solid. Yield: 80%. Mp: 62 ꢀC; 1H NMR (200 MHz, CDCl3)
d
9.75 (s, 1H), 8.55 (d, J¼4.6 Hz, 1H), 7.99 (d, J¼7.8 Hz, 1H), 7.65 (t,
J¼7.4 Hz, 1H), 7.51 (m, 2H), 7.21 (m, 2H), 2.32 (s, 3H); 13C NMR
(50 MHz, CDCl3) d 190.4,155.5,148.2,142.2,137.0,133.4,133.1,130.2,
Melting points were measured on a Totoli apparatus. 1H NMR
spectra were recorded on a Brucker AC200 (200 MHz) and data are
reported as follows: chemical shifts in parts per million from TMS
as an internal standard, multiplicity (s¼singlet, d¼doublet,
t¼triplet, q¼quartet, m¼multiplet or overlap of non-equivalent
resonances), integration. 13C NMR spectra were recorded at 50 MHz
and data are reported as follows: chemical shifts in parts per mil-
127.9, 127.7, 120.2, 22.6. MS (EI) m/z 197 (Mþ, 95%), 196 ([Mꢁ1]þ,
100), 182 (75), 168 (65), 167 (58), 128 (48). HRMS m/z calcd for
C13H11NO: 197.0841, found: 198.0913 (MHþ).
4.2.3. 2-(3-Methyl-pyridin-3-yl)-benzaldehyde (3c)
Yellow solid. Yield: 90%. Mp: 65 ꢀC; 1H NMR (200 MHz, CDCl3)
d
9.75 (s, 1H), 8.56 (s, 1H), 8.53 (d, J¼4.8 Hz, 1H), 8.06 (d, J¼7.6 Hz,
lion from TMS as an internal indicator (CDCl3,
d
77.0 ppm). Mass
1H), 7.71 (t, J¼7.2 Hz, 1H), 7.59 (t, J¼7.4 Hz, 1H), 7.27 (d, J¼7.6 Hz,
spectra with electronic impact (MS-EI) were recorded from a Shi-
madzu QP 2010 apparatus. High resolution mass spectra were
recorded from a Brucker micrOTOF-Q. THF was distilled from so-
dium/benzophenone and stored on sodium wire before use. Dii-
sopropylamine, toluene, benzene, DMA (dimethylacetamide), ethyl
acetate, and dimethylcarbonate were distilled over CaH2. Methanol,
DMF, and ethylene glycol were used as received. All reagents were
used as received. TLC was performed on silica gel plates and visu-
alized with a UV lamp (254 nm). Chromatography was performed
on silica gel (70–230 mesh).
1H), 7.15 (d, J¼4.8 Hz, 1H), 2.11 (s, 3H); 13C NMR (50 MHz, CDCl3)
d
190.9, 150.7, 147.0, 145.9, 136.1, 134.0, 133.0, 131.5, 129.8, 128.7,
128.1, 124.3, 17.0. MS (EI) m/z 197 (Mþ, 100%), 182 (37), 167 (25), 127
(14), 115 (22). HRMS m/z calcd for C13H11NO: 197.0841, found:
198.0913 (MHþ).
4.2.4. 2-(2,4,6-Trimethyl-pyridin-3-yl)-benzaldehyde (3d)
White solid. Yield: 93%. Mp: 58 ꢀC; 1H NMR (200 MHz, CDCl3)
d
9.70 (s, 1H), 8.03 (d, J¼7.6 Hz, 1H), 7.68 (t, J¼7.4 Hz, 1H), 7.53 (t,
J¼7.6 Hz, 1H), 7.19 (d, J¼7.6 Hz, 1H), 6.96 (s, 1H), 2.54 (s, 3H), 2.18 (s,
3H), 1.93 (s, 3H); 13C NMR (50 MHz, CDCl3)
191.3, 157.0, 155.1,
d
4.2. Preparation of aldehydes 3
145.8, 142.4, 134.4, 133.6, 130.1, 129.7, 128.2, 128.1, 122.0, 24.0, 23.5,
20.1. MS (EI) m/z 225 (Mþ, 100%), 210 (50), 196 (83), 115 (22). HRMS
m/z calcd for C15H15NO: 225.1154, found: 226.1226 (MHþ).
4.2.1. A representative procedure for the Suzuki coupling of pyridine
1 with boronic acid 2: preparation of 2-(4-methyl-pyridin-3-yl)-
benzaldehyde (3b)
3-Bromo-4-methyl-pyridine 1b (860 mg, 5 mmol) was added to
a degazed toluene solution (20 mL) containing Pd(PPh3)4 (290 mg,
0.25 mmol). To the mixture under N2 were added successively
a degazed solution of boronic acid 2a (825 mg, 5.5 mmol) in
methanol (10 mL) and a degazed solution of Na2CO3 (1.06 g,
10 mmol) in water (10 mL). After heating for 15 h at 90 ꢀC, the
4.2.5. 2-(5-Bromo-2,4,6-trimethyl-pyridin-3-yl)-benzaldehyde (3e)
White solid. Yield: 53%. Mp: 108 ꢀC; 1H NMR (200 MHz, CDCl3)
d
9.74 (s, 1H), 8.06 (d, J¼7 Hz, 1H), 7.72 (t, J¼7 Hz, 1H), 7.60 (t,
J¼6.8 Hz, 1H), 7.20 (d, J¼7 Hz, 1H), 2.73 (s, 3H), 2.14 (s, 3H), 2.09 (s,
3H); 13C NMR (50 MHz, CDCl3)
190.7, 156.1, 153.4, 145.4, 141.6,
134.5, 133.5, 131.5, 130.5, 128.7, 128.6, 122.0, 25.7, 23.2, 21.4. MS (EI)
m/z 305 (Mþ 81Br], 97%), 303 (Mþ 79Br], 100), 290 (50), 288 (55),
d
[
[

V. Mamane et al. / Tetrahedron 64 (2008) 10699–10705
10703
276 (92), 274 (95), 224 (32), 209 (30), 194 (35), 181 (27), 152 (38),
115 (26), 76 (36). HRMS m/z calcd for C15H14BrNO: 303.0259, found:
304.0332 (MHþ).
124.5, 123.0, 115.9. MS (EI) m/z 179 (Mþ, 100%), 151 (16), 89 (13),
76 (18).
4.3.4. 1,3-Dimethylbenzo[h]isoquinoline (4d)
4.2.6. 2-(6-Dimethylamino-2,4-dimethyl-pyridin-3-yl)-
White solid. Yield: 51%. Mp: 112 ꢀC; 1H NMR (200 MHz, CDCl3)
benzaldehyde (3f)
d
8.71 (d, J¼8.2 Hz, 1H), 8.81 (d, J¼7 Hz, 1H), 7.72 (d, J¼8.8 Hz, 1H),
7.57 (t, J¼7.6 Hz, 1H), 7.43 (d, J¼8.8 Hz, 1H), 7.28 (s, 1H), 3.23 (s, 3H),
2.64 (s, 3H); 13C NMR (50 MHz, CDCl3)
156.2, 151.6, 138.3, 133.0,
Yellow oil. Yield: 42%. 1H NMR (200 MHz, CDCl3)
d 9.78 (s, 1H),
8.01 (d, J¼7.6 Hz, 1H), 7.63 (t, J¼7.4 Hz, 1H), 7.47 (t, J¼7.4 Hz, 1H),
d
7.20 (d, J¼7.4 Hz, 1H), 6.31 (s, 1H), 3.11 (s, 6H), 2.09 (s, 3H), 1.90 (s,
131.3,130.4,128.9,128.4,126.8,126.7,126.0,125.6,125.2,125.1,118.6,
30.2, 23.8. MS (EI) m/z 206 ([Mꢁ1]þ,100%),191 (10). HRMS m/z calcd
for C15H13N: 207.1048, found: 208.1121 (MHþ).
3H); 13C NMR (50 MHz, CDCl3)
d 192.2, 158.5, 153.9, 146.5, 143.9,
134.4, 134.1, 131.6, 127.6, 127.2, 120.2, 103.7, 37.7, 23.7, 20.9. MS (EI)
m/z 254 (Mþ, 100%), 239 (74), 225 (100), 211 (36), 182 (22). HRMS
m/z calcd for C16H18N2O: 254.1419, found: 255.1492 (MHþ).
4.3.5. 4-Bromo-1,3-dimethylbenzo[h]isoquinoline (4e)
White solid. Yield: 44%. Mp: 98 ꢀC; 1H NMR (200 MHz, CDCl3)
4.2.7. 6-(2-Methyl-pyridin-3-yl)-benzo[1,3]dioxole-5-
d
8.68 (d, J¼8 Hz, 1H), 8.06 (d, J¼9 Hz, 1H), 7.83 (m, 2H), 7.61 (m,
carbaldehyde (3g)
2H), 3.17 (s, 3H), 2.81 (s, 3H); 13C NMR (50 MHz, CDCl3)
d
154.6,
Colorless oil. Yield: 72%. 1H NMR (200 MHz, CDCl3)
d
9.47 (s, 1H),
150.9, 132.7, 132.5, 129.9, 128.9, 127.1, 126.7, 126.6, 124.5, 122.8,
118.2, 29.9, 25.5. MS (EI) m/z 285 (Mþ, 100%), 205 (42), 190 (20), 163
(20), 103 (27), 82 (25). HRMS m/z calcd for C15H12BrN: 285.0153,
found: 286.0226 (MHþ).
8.53 (d, J¼4.2 Hz, 1H), 7.48 (d, J¼7.6 Hz, 1H), 7.41 (s, 1H), 7.21 (t,
J¼5 Hz, 1H), 6.67 (s, 1H), 6.10 (s, 2H), 2.33 (s, 3H); 13C NMR (50 MHz,
CDCl3)
d 189.0, 156.3, 152.3, 148.7, 148.0, 137.7, 132.4, 128.6, 120.5,
109.8, 106.1, 102.1, 22.9. MS (EI) m/z 241 (Mþ, 75%), 226 (100), 154
(17). HRMS m/z calcd for C14H11NO3: 241.0739, found: 242.0812
(MHþ).
4.3.6. 3-Dimethylamino-1-methylbenzo[h]isoquinoline (4f)
Greenish solid. Yield: 42%. Mp: 80 ꢀC; 1H NMR (200 MHz, CDCl3)
d
8.59 (d, J¼8.6 Hz, 1H), 7.72 (d, J¼7.4 Hz, 1H), 7.58 (d, J¼9 Hz, 1H),
4.2.8. 6-(4-Methyl-pyridin-3-yl)-benzo[1,3]dioxole-5-
carbaldehyde (3h)
7.52 (d, J¼8.6 Hz, 1H), 7.37 (t, J¼8.2 Hz, 2H), 3.15 (s, 3H), 3.13 (s, 6H);
13C NMR (50 MHz, CDCl3)
d 156.6, 156.5, 140.8, 131.5, 130.9, 128.8,
White solid. Yield: 98%. Mp: 134 ꢀC; 1H NMR (200 MHz, CDCl3)
126.7,126.2,126.1,125.9,124.4, 98.4, 37.9, 30.2. MS (EI) m/z 236 (Mþ,
100%), 221 (66), 207 (100), 193 (29), 165 (45), 118 (23). HRMS m/z
calcd for C16H16N2: 236.1313, found: 237.1386 (MHþ).
d
948 (s, 1H), 8.51 (d, J¼4.8 Hz, 1H), 8.39 (s, 1H), 7.44 (s, 1H), 7.24 (d,
J¼4.8 Hz, 1H), 6.69 (s, 1H), 6.12 (s, 2H), 2.15 (s, 3H); 13C NMR
(50 MHz, CDCl3)
d 189.0, 152.3, 149.5, 148.8, 148.2, 145.9, 138.0,
133.5, 129.0, 124.7, 110.1, 106.2, 102.2. MS (EI) m/z 241 (Mþ, 100%),
226 (55), 212 (15), 154 (17). HRMS m/z calcd for C14H11NO3:
241.0739, found: 242.0812 (MHþ).
4.3.7. [1,3]Benzodioxolo[5,6-f]quinoline (4g)6a
White solid. Yield: 65%. Mp: 193 ꢀC; 1H NMR (200 MHz, CDCl3)
d
8.90 (d, J¼3.8 Hz,1H), 8.68 (d, J¼8.4 Hz,1H), 7.84 (m, 3H), 7.47 (dd,
J¼8.2 4.2 Hz, 1H), 7.21 (s, 1H), 6.10 (s, 2H); 13C NMR (50 MHz, CDCl3)
4.3. Preparation of benzo-(iso)quinolines 4
d 148.9, 148.5, 148.1, 147.1, 130.3, 130.1, 128.0, 126.3, 125.8, 125.0,
120.8, 105.7, 101.5, 100.5. MS (EI) m/z 223 (Mþ, 100%), 164 (16), 138
4.3.1. A representative procedure for the t-BuOK-promoted
cyclization of aldehydes 3: preparation of
(14), 111 (17).
benzo[h]isoquinoline (4b)9
4.3.8. [1,3]Benzodioxolo[5,6-h]isoquinoline (4h)6a
To a solution of compound 3b (788 mg, 4 mmol) in DMF (4 mL)
was slowly added at room temperature a solution of t-BuOK
(896 mg, 8 mmol) in DMF (8 mL) and the mixture was stirred
overnight. The reaction mixture was quenched by addition of water
(1 mL) and extracted with dichloromethane (4ꢂ20 mL). After dry-
ing over MgSO4 and concentration, the residue was purified by
chromatography (hexanes/ethyl acetate/triethylamine 8:1:1) to
afford 4b as a white solid (560 mg, 78%). Mp: 50 ꢀC; 1H NMR
White solid. Yield: 88%. Mp: 178 ꢀC; 1H NMR (200 MHz, CDCl3)
d
9.75 (s, 1H), 8.56 (d, J¼5.2 Hz, 1H), 7.99 (s, 1H), 7.70 (d, J¼8.8 Hz,
1H), 7.58 (d, J¼5.2 Hz, 1H), 7.48 (d, J¼8.8 Hz, 1H), 7.14 (s, 1H), 6.07 (s,
2H); 13C NMR (50 MHz, CDCl3)
148.9, 148.1, 146.5, 143.7, 134.8,
d
130.9, 128.7, 126.3, 124.8, 123.0, 121.0, 105.9, 101.6, 99.9. MS (EI) m/z
223 (Mþ, 100%), 164 (18), 138 (15), 111 (17).
4.4. Preparation of 2-chlorobenzo[h]quinoline 12
(200 MHz, CDCl3)
d
10.07 (s, 1H), 8.82 (d, J¼8.4 Hz, 1H), 8.72 (d,
J¼5.2 Hz, 1H), 7.96 (d, J¼8.8 Hz, 2H), 7.73 (m, 4H); 13C NMR
4.4.1. A representative procedure for the Negishi reaction of 6 with
bromopyridines. Preparation of 2-(2-[1,3]dioxolan-2-yl-phenyl)-3-
methyl-pyridine (7)
(50 MHz, CDCl3) d 146.5,144.8,135.5,131.8,131.3,128.9,128.6,127.5,
127.1, 124.5, 124.7, 121.6, 120.9. MS (EI) m/z 179 (Mþ, 100%), 151 (19),
76 (15).
A solution of 6 (486 mg, 2 mmol) in dry THF (1 mL) was added to
a cooled solution of t-BuLi (1.7 M in pentane, 2.35 mL, 4 mmol) in
dry THF (4 mL) at ꢁ78 ꢀC under nitrogen. After 30 min at ꢁ78 ꢀC,
a solution of freshly dried ZnCl2 in THF (0.5 M, 4.3 mL, 4.28 mmol)
was added slowly and the temperature was raised to room tem-
perature and stirred for 2 h. To the clear solution were successively
added pyridine 1g (287 mg, 1.67 mmol) and Pd(PPh3)4 (77 mg,
0.067 mmol) and the mixture was stirred at reflux overnight. Brine
was added, the mixture was extracted with ethyl acetate (15 mL),
dried over MgSO4, and concentrated. The residue was purified by
chromatography (hexanes/ethyl acetate 4:1) to afford 7 as a color-
4.3.2. Benzo[f]quinoline (4a)9
White solid. Yield: 80%. Mp: 93 ꢀC; 1H NMR (200 MHz, CDCl3)
d
8.97 (s, 1H), 8.94 (d, J¼6.2 Hz, 1H), 8.62 (m, 1H), 7.99 (s, 1H), 7.96
(dd, J¼6.6, 2.2 Hz, 1H), 7.92 (d, J¼2.2 Hz, 1H), 7.67 (m, 2H), 7.55 (dd,
J¼8.4, 4.6 Hz, 1H); 13C NMR (50 MHz, CDCl3)
d 149.9, 149.4, 131.8,
131.0, 130.8, 129.8, 128.8, 128.3, 127.5, 127.2, 125.6, 122.7, 121.4. MS
(EI) m/z 179 (Mþ, 100%), 151 (22), 76 (18).
4.3.3. Benzo[f]isoquinoline (4c)9
White solid. Yield: 60%. Mp: 90 ꢀC; 1H NMR (200 MHz, CDCl3)
less oil (262 mg, 65%). 1H NMR (200 MHz, CDCl3)
d
8.43 (d, J¼4.2 Hz,
d
9.18 (s, 1H), 8.69 (d, J¼5.6 Hz, 1H), 8.53 (t, J¼4.6 Hz, 1H), 8.27 (d,
1H), 7.67 (m, 1H), 7.47 (d, J¼7.6 Hz, 1H), 7.34 (m, 2H), 7.11 (m, 2H),
J¼5.4 Hz, 1H), 7.84 (m, 1H), 7.80–7.55 (m, 4H); 13C NMR (50 MHz,
5.56 (s, 1H), 3.89 (m, 2H), 3.68 (m, 2H), 2.07 (s, 3H); 13C NMR
CDCl3)
d
151.5, 145.0, 134.6, 133.3, 128.6, 128.5, 128.2, 127.0, 126.8,
(50 MHz, CDCl3) d 157.5, 145.5, 139.5, 136.9, 134.9, 131.4, 128.1, 128.0,

10704
V. Mamane et al. / Tetrahedron 64 (2008) 10699–10705
127.3, 125.9, 121.7, 100.4, 64.4, 18.6. MS (EI) m/z 240 ([MꢁH]þ, 5%),
3H); 13C NMR (50 MHz, CDCl3)
d 154.9, 146.3, 140.3, 136.5, 133.9,
182 (15), 168 (100).
133.0, 131.9, 128.6, 128.3, 127.7, 127.1, 127.0, 126.4, 126.2, 125.1, 124.6,
118.4, 14.2. MS (EI) m/z 301 (Mþ, 100%), 253 (12), 226 (15), 142 (22),
127 (21). HRMS m/z calcd for C20H15NS: 301.0925, found: 302.0998
(MHþ).
4.4.2. 6-Chloro-2-(2-[1,3]dioxolan-2-yl-phenyl)-3-
methyl-pyridine (10)
Yellow solid. Yield: 50%. Mp: 107 ꢀC; 1H NMR (200 MHz, CDCl3)
d
7.63 (m, 1H), 7.48 (d, J¼8 Hz, 1H), 7.37 (d, J¼5 Hz, 1H), 7.36 (d,
J¼4.6 Hz, 1H), 7.14 (m, 2H), 5.61 (s, 1H), 3.90 (m, 2H), 3.78 (m, 2H),
2.05 (s, 3H); 13C NMR (50 MHz, CDCl3)
158.5, 147.2, 140.3, 138.5,
4.6. Preparation of acetals 16
d
4.6.1. 3-(2-[1,3]Dioxolan-2-yl-phenyl)-2-methyl-pyridine (16a)
Aldehyde 3a (320 mg, 1.624 mmol) was dissolved in benzene
(60 mL). Ethylene glycol (15 mL) and p-TSA (15.6 mg, 0.08 mmol)
were added and the mixture was heated at 100 ꢀC with a Dean–
Stark apparatus overnight. After cooling the reaction, a saturated
solution of NaHCO3 (30 mL) was added and the organic phase was
separated and dried over MgSO4. After filtration and concentration,
the crude was purified by chromatography on silica gel (hexane/
ethyl acetate 1:1) to give 16a as a colorless oil (323 mg, 83%). 1H
135.5, 131.1, 128.7, 128.6, 128.2, 126.5, 122.6, 101.1, 65.0, 18.4. MS (EI)
m/z 202 ([MꢁC3H6O2]þ, 100%), 166 (20). HRMS m/z calcd for
C15H14ClNO2: 275.0713, found: 276.0786 (MHþ).
4.4.3. 2-(6-Chloro-3-methyl-pyridin-2-yl)-benzaldehyde (11)
Compound 10 (100 mg, 0.344 mmol) was dissolved in THF
(2 mL), water (0.2 mL) and p-TSA (130 mg, 0.688 mmol) were
added and the mixture was stirred at room temperature for 2 h. A
saturated solution of NaHCO3 was added and the mixture was
extracted with ethyl acetate (10 mL), dried over MgSO4 and con-
centrated. The residue was purified by chromatography (hexanes/
ethyl acetate 4:1) to afford aldehyde 11 (70 mg, 81%), which was
used directly in the cyclization step. 1H NMR (200 MHz, CDCl3)
NMR (200 MHz, CDCl3)
d
8.46 (d, J¼3.8 Hz,1H), 7.64 (m,1H), 7.44 (d,
J¼7.8 Hz, 1H), 7.40 (d, J¼7.4 Hz, 1H), 7.36 (d, J¼3.6 Hz, 1H), 7.10 (m,
2H), 5.38 (s, 1H), 3.90–3.70 (m, 4H), 2.30 (s, 3H); 13C NMR (50 MHz,
CDCl3)
d 156.4, 148.1, 139.1, 137.5, 135.1, 134.7, 129.5, 129.0, 128.0,
126.9, 120.2, 101.5, 65.2, 65.1, 23.2. MS (EI) m/z 240 ([Mꢁ1]þ, 35%),
226 (100), 196 (64), 180 (92), 167 (54), 148 (96), 139 (20), 104 (26),
73 (36). HRMS m/z calcd for C15H15NO2: 241.1103, found: 242.1176
(MHþ).
d
9.78 (s, 1H), 7.98 (d, J¼7.4 Hz), 7.70–7.50 (m, 3H), 7.35 (d, J¼7.2 Hz,
1H), 7.27 (d, J¼8 Hz, 1H), 2.10 (s, 3H).
4.4.4. 2-Chlorobenzo[h]quinole (12)1f
This compound was obtained using the same procedure as for 4.
4.6.2. 3-(2-[1,3]Dioxolan-2-yl-phenyl)-4-methyl-pyridine (16b)
Yellow solid. Yield: 67%. Mp: 105 ꢀC; 1H NMR (200 MHz, CDCl3)
Colorless oil. Yield: 86%. 1H NMR (200 MHz, CDCl3)
d 8.43 (d,
d
9.17 (d, J¼8.3 Hz, 1H), 8.02 (d, J¼8.3 Hz, 1H), 7.67–7.79 (m, 4H),
J¼5 Hz, 1H), 8.38 (s, 1H), 7.67 (m, 1H), 7.40 (m, 2H), 7.15 (d, J¼5 Hz,
7.57 (d, J¼8.7 Hz, 1H), 7.43 (d, J¼8.3 Hz, 1H); 13C NMR (50 MHz,
1H), 7.09 (m, 1H), 5.41 (s, 1H), 3.90–3.75 (m, 4H), 2.08 (s, 3H); 13C
CDCl3)
d
156.6, 149.8, 138.5, 133.9, 130.4, 128.8, 128.1, 127.8, 127.3,
NMR (50 MHz, CDCl3) d 149.7, 148.3, 145.5, 137.1, 135.6, 135.5, 129.8,
124.9, 124.7, 124.5, 122.6. MS (EI) m/z 214 (Mþ, 100%), 178 (72).
128.8, 128.0, 126.8, 124.4, 101.4, 65.1, 19.5. MS (EI) m/z 240 ([Mꢁ1]þ,
100%), 196 (38), 168 (31), 148 (62), 104 (14), 73 (17). HRMS m/z calcd
for C15H15NO2: 241.1103, found: 242.1176 (MHþ).
4.5. Suzuki coupling of 12
Compounds 16a and 16b were also obtained using the same
procedure as for 7 and 10; 16a (67%) and 16b (68%).
4.5.1. Representative procedure. Preparation of 2-
phenylbenzo[h]quinole (13)4f
2-Chlorobenzo[h]quinole 12 (100 mg, 0.47 mmol) was added to
a degazed toluene solution (2 mL) containing Pd(PPh3)4 (27 mg,
0.024 mmol). To the mixture under N2 were added successively
a degazed solution of boronic acid 2a (110 mg, 0.7 mmol) in
methanol (1 mL) and a degazed solution of NaHCO3 (80 mg,
0.94 mmol) in water (1 mL). After heating for 15 h at 90 ꢀC, the
reaction mixture was cooled to room temperature, extracted with
ethyl acetate (10 mL) and dried over MgSO4. After concentration,
the residue was purified by chromatography (hexanes/ethyl acetate
4:1) to give compound 13 as a white solid (76 mg, 67%). Mp: 65 ꢀC;
4.7. Preparation of benzo-(iso)quinolines 17 and 18
4.7.1. 1-Benzo[f]quinolin-5-yl-ethanone (17a)
Acetal 16a (100 mg, 0.415 mmol) was dissolved in THF (2 mL)
and the solution was cooled to ꢁ30 ꢀC. n-BuLi (1.6 M in hexanes,
0.52 mL, 0.83 mmol) was added slowly and the mixture was stirred
at ꢁ20 ꢀC for 1 h. After cooling to ꢁ78 ꢀC, DMA (85
mL, 0.913 mmol)
was added and the solution was stirred for 1 h. Hydrolysis was
performed at ꢁ78 ꢀC then the temperature was raised to ambiant.
p-TSA (800 mg, 4.2 mmol) was added and the mixture was stirred
at room temperature overnight. NaHCO3 satd (5 mL) was added and
the mixture was extracted with ethyl acetate (20 mL), dried over
MgSO4 and concentrated. The crude was purified by chromato-
graphy (hexanes/ethyl acetate 4:1) to give 17a as a yellow solid
1H NMR (200 MHz, CDCl3)
1H), 8.04 (d, J¼8.4 Hz, 1H), 7.86 (d, J¼8.2 Hz, 1H), 7.83 (d, J¼8.2 Hz,
1H), 7.42–7.70 (m, 7H); 13C NMR (50 MHz, CDCl3)
155.4, 146.2,
d
9.48 (d, J¼7.9 Hz, 1H), 8.29 (d, J¼7.2 Hz,
d
139.7, 136.5, 133.9, 131.9, 129.3, 128.9, 128.2, 127.8, 127.5, 127.4,
126.9,125.2,125.1,124.8,118.8. MS (EI) m/z 255 (Mþ,100%),127 (18).
(50 mg, 55%). Mp: 110 ꢀC; 1H NMR (200 MHz, CDCl3)
d 8.96 (d,
J¼4.2 Hz, 1H), 8.91 (d, J¼8.6 Hz, 1H), 8.55 (d, J¼8 Hz, 1H), 8.17 (s,
4.5.2. 2-Benzo[h]quinolin-2-yl-benzaldehyde (14)
1H), 7.96 (d, J¼7 Hz, 1H), 7.72 (m, 2H), 7.56 (dd, J¼8.4, 4.4 Hz, 1H);
White solid. Yield: 76%. Mp: 115 ꢀC; 1H NMR (200 MHz, CDCl3)
13C NMR (50 MHz, CDCl3)
d 190.9, 156.4, 149.1, 138.5, 132.4, 130.7,
d
10.36 (s, 1H), 9.20 (d, J¼8.3 Hz, 1H), 8.29 (d, J¼8.4 Hz, 1H), 8.06 (d,
130.2, 129.8, 129.2, 128.5, 127.7, 125.4, 122.4, 121.5, 32.4. MS (EI) m/z
221 (Mþ,100%), 206 (94),178 (60),151 (46), 75 (16). HRMS m/z calcd
for C15H11NO: 221.0841, found: 222.0913 (MHþ).
J¼7.6 Hz, 1H), 7.50–8.00 (m, 9H); 13C NMR (50 MHz, CDCl3)
d 193.2,
154.2,143.0,137.0,136.3,133.9,133.5,132.8,131.6,129.9,129.1,128.9,
128.6, 128.5, 128.4, 127.9, 127.6, 125.0, 124.9, 121.9. MS (EI) m/z 255
([MꢁCO]þ,100%),127 (18). HRMS m/z calcd for C20H13NO: 283.0997,
found: 284.1070 (MHþ).
4.7.2. A representative procedure for the reaction of acetals 16 with
NDA. Preparation of benzo[f]quinoline-5-carboxylic acid
methyl ester (18a)
4.5.3. 2-(4-Thiomethyl-phenyl)benzo[h]quinoline (15)
t-BuONa (140 mg, 1.45 mmol) was dried for 2 h at 100 ꢀC in
White solid. Yield: 79%. Mp: 128 ꢀC; 1H NMR (200 MHz, CDCl3)
9.46 (d, 7.9 Hz, 1H), 8.24 (d, J¼7.7 Hz, 1H), 8.12 (d, J¼8.4 Hz, 1H),
vacuo. THF (3 mL) and diisopropylamine (187 mL, 1.45 mmol) were
d
added and the mixture was cooled to ꢁ78 ꢀC. n-BuLi (1.6 M in
7.85–7.95 (m, 2H), 7.60–7.80 (m, 4H), 7.38 (d, J¼8.7 Hz, 2H), 2.53 (s,
hexane, 0.9 mL, 1.45 mmol) was added dropwise and the mixture

V. Mamane et al. / Tetrahedron 64 (2008) 10699–10705
10705
Trans. 1 1999, 2315–2321; (f) Cappelli, A.; Anzini, M.; Vomero, S.; Mennuni, L.;
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was stirred for 15 min at the same temperature. Acetal 16b
(100 mg, 0.415 mmol) dissolved in THF (2 mL) was added dropwise
and the resulting solution was stirred for 30 min at ꢁ78 ꢀC.
Dimethylcarbonate (200 mL,1.66 mmol) was added and the mixture
was stirred for 1 h. Water (1 mL) was added at ꢁ78 ꢀC and the
temperature was raised to ambient temperature before addition of
p-TSA (1.6 g, 8.4 mmol) and stirring was maintained overnight.
NaHCO3 satd (10 mL) was added and the mixture was extracted
with ethyl acetate (30 mL), dried over MgSO4 and concentrated. The
crude was purified by chromatography (hexanes/ethyl acetate 4:1)
to give 18a as a yellow oil (72 mg, 73%). 1H NMR (200 MHz, CDCl3)
4. (a) Wang, X.-S.; Li, Q.; Yao, C.-S.; Tu, S.-J. Eur. J. Org. Chem. 2008, 3513–3515; (b)
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Ahmed, E.; Chen, X.; Cox, M.; Crew, A. P.; Dong, H.-Q.; Jin, M.; Ma, L.; Panicker,
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d
9.02 (d, J¼4.2 Hz,1H), 8.83 (d, J¼8.4 Hz, 1H), 8.47 (d, J¼8.2 Hz, 1H),
8.26 (s, 1H), 7.88 (d, J¼7.2 Hz, 1H), 7.63 (m, 2H), 7.51 (dd, J¼8.4,
4.4 Hz, 1H), 4.08 (s, 3H); 13C NMR (50 MHz, CDCl3)
168.0, 149.8,
d
132.1, 130.6, 130.4, 130.0, 129.6, 129.1, 128.5, 127.5, 125.3, 122.3,
121.5, 52.5. MS (EI) m/z 237 (Mþ, 40%), 206 (46), 179 (100), 151 (28),
89 (13), 75 (17). HRMS m/z calcd for C15H11NO2: 237.0790, found:
238.0863 (MHþ).
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Yellow solid. Yield: 44%. Mp: 135 ꢀC; 1H NMR (200 MHz, CDCl3)
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d
9.94 (s,1H), 8.68 (m, 3H), 8.36 (s,1H), 7.93 (d, J¼7.4 Hz,1H), 7.78 (t,
J¼7.2 Hz, 1H), 7.66 (t, J¼7 Hz, 1H), 2.79 (s, 3H); 13C NMR (50 MHz,
CDCl3)
d 199.8, 146.5, 145.9, 135.8, 132.6, 131.3, 130.9, 130.2, 130.1,
129.8, 128.6, 127.9, 125.0, 121.7, 119.5, 29.1. MS (EI) m/z 221 (Mþ,
60%), 206 (100), 178 (49), 151 (30). HRMS m/z calcd for C15H11NO:
221.0841, found: 222.0913 (MHþ).
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12. Cassity, R. P.; Taylor, L. T.; Wolfe, J. F. J. Org. Chem. 1978, 43, 2286–2288.
13. (a) Pathak, R.; Vandayar, K.; van Otterlo, W. A. L.; Michael, J. P.; Fernandes, M. A.;
de Koning, C. B. Org. Biomol. Chem. 2004, 2, 3504–3509; (b) de Koning, C. B.;
Michael, J. P.; Nhlapo, J. M.; Pathak, R.; van Otterlo, W. A. L. Synlett 2003, 705–
707; (c) de Koning, C. B.; Michael, J. P.; Rousseau, A. J. Chem. Soc., Perkin Trans. 1
2000, 1705–1713; (d) de Koning, C. B.; Michael, J. P.; Rousseau, A. J. Chem. Soc.,
Perkin Trans. 1 2000, 787–797.
4.7.4. Benzo[h]isoquinoline-5-carboxylic acid ethyl ester (18b)
White solid. Yield: 40%. Mp: 95 ꢀC; 1H NMR (200 MHz, CDCl3)
d
10.05 (s,1H), 8.78 (m, 3H), 8.69 (s,1H), 7.99 (d, J¼7.8 Hz, 1H), 7.82 (t,
J¼7.2 Hz,1H), 7.68 (t, J¼7 Hz,1H), 4.51 (q, J¼7 Hz, 2H),1.50 (t, J¼7.2 Hz,
3H); 13C NMR (50 MHz, CDCl3)
166.3,146.8,145.8,137.0,131.2,130.4,
d
14. Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457–2483.
130.2, 128.7, 128.5,127.9, 125.1, 124.2, 121.9,119.3, 61.4,14.4. MS (EI) m/z
251 (Mþ, 83%), 223 (22), 206 (100), 178 (42), 151 (28). HRMS m/z calcd
for C16H13NO2: 251.0946, found: 252.1019 (MHþ).
15. (a) For the synthesis of compound 1a see: Pasquinet, E.; Rocca, P.; Richalot, S.;
Gue´ritte, F.; Gue´nard, D.; Godard, A.; Marsais, F.; Que´guiner, G. J. Org. Chem.
2001, 66, 2654–2661; (b) For the synthesis of compound 1c see: Spivey, A. C.;
Shukla, L.; Hayler, J. F. Org. Lett. 2007, 9, 891–894.
16. (a) For compounds 1d and 1e see: Mal, P.; Lourderaj, U.; Parveen, P.; Ven-
ugopalan, P.; Narasimba Moorthy, J.; Sathyamurthy, N. J. Org. Chem. 2003, 68,
3446–3453; (b) For compound 1f see: Wijtmans, M.; Pratt, D. A.; Brinkhorst, J.;
Serwa, R.; Valgimigli, L.; Pedulli, G. F.; Porter, N. A. J. Org. Chem. 2004, 69, 9215–
9223.
Acknowledgements
We gratefully acknowledge the CNRS and the University of
Nancy for financial support. F. Dupire and S. Adach (Service Com-
mun d’Analyse of the Jean Barriol Institut) are acknowledged for
their technical assistance.
17. The connectivity information was unambiguously established by analysis of
NMR data using HMBC technique.
18. Mamane, V.; Aubert, E.; Fort, Y. J. Org. Chem. 2007, 72, 7294–7300.
19. (a) Mamane, V.; Fort, Y. Tetrahedron Lett. 2006, 47, 2337–2340; (b) Mamane,
V. Targets in Heterocyclic Systems. In Chemistry and Properties. Attanasi, O.,
Spinelli, D., Eds.; Societa` Chimica Italiana (SCI): Urbino, Italy, 2006; Vol. 10,
pp 197–231.
References and notes
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23. For metal-catalyzed amination of similar structures see: Desmarets, C.;
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24. For a recent related work in phenanthrene synthesis see: Kim, Y. H.; Lee, H.;
Kim, Y. J.; Kim, B. T.; Heo, J.-N. J. Org. Chem. 2008, 73, 495–501.
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