Regioselective synthesis of amino- and nitroarenes based on [3+3] cyclocondensations of 1,3-bis(silyloxy)-1,3-butadienes

Article abstract of DOI:10.1016/j.tet.2009.09.014

Functionalized amino- and nitro-substituted biaryls and dibenzo[b,d]pyrid-6-ones (6(5H)-phenanthridinones) were prepared by [3+3]cyclocondensation of 1,3-bis(trimethylsilyloxy)-1,3-butadienes with nitro-substituted 1-aryl-1-silyloxy-1-en-3-ones and subsequent hydrogenation. 4-Nitro- and 4-aminophenols were prepared based on formal [3+3] cyclizations of 1,3-bis(trimethylsilyloxy)-1,3-butadienes with 3-ethoxy-2-nitro-2-en-1-ones.

Full text of DOI:10.1016/j.tet.2009.09.014

Tetrahedron 65 (2009) 9300–9315
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Regioselective synthesis of amino- and nitroarenes based on [3þ3]
cyclocondensations of 1,3-bis(silyloxy)-1,3-butadienes
,
Abdolmajid Riahi a b, Mohanad Shkoor a, Olumide Fatunsin a, Mirza A. Yawer a,
,b,
Ibrar Hussain a, Christine Fischer b, Peter Langer a
*
a
¨
Institut fu¨r Chemie, Universitat Rostock, Albert-Einstein-Str. 3a, 18059 Rostock, Germany
b Leibniz-Institut fu¨r Katalyse e. V. an der Universita¨t Rostock, Albert-Einstein-Str. 29a, 18059 Rostock, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 30 April 2009
Received in revised form 25 August 2009
Accepted 3 September 2009
Available online 9 September 2009
Functionalized amino- and nitro-substituted biaryls and dibenzo[b,d]pyrid-6-ones (6(5H)-phenan-
thridinones) were prepared by [3þ3]cyclocondensation of 1,3-bis(trimethylsilyloxy)-1,3-butadienes with
nitro-substituted 1-aryl-1-silyloxy-1-en-3-ones and subsequent hydrogenation. 4-Nitro- and 4-amino-
phenols were prepared based on formal [3þ3] cyclizations of 1,3-bis(trimethylsilyloxy)-1,3-butadienes
with 3-ethoxy-2-nitro-2-en-1-ones.
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
Arenes
Cyclizations
Nitro compounds
Regioselectivity
Silyl enol ethers
1. Introduction
chelirubinone, oxychelirubine, arolycoricidine, pratosine, tur-
raeanthin B, or kalbretorine, are known.12
Functionalized 4-nitro- and 4-aminophenols are of considerable
pharmacological relevance and occur in several natural products.1
4-Nitrophenols show antiandrogenetic,2a vasodilative,2b and es-
trogenic activity.2c A wide range of pharmacological activities has
been reported for functionalized 4-aminophenols and related
molecules.3–8 Amino- and nitro-substituted biaryl derivatives are
also of considerable current interest, due to their anti-hepatitis and
antimalarial activity, binding affinity to C5a receptor (human
monocyte cell line U937), inhibition of cyclic nucleotide phos-
phorodiesterases (PDEs), and activity for topoisomerases I and
II-mediated DNA cleavage.8 Dibenzo[b,d]pyrid-6-ones (6(5H)-phe-
nanthridinones) can be regarded as lactams derived from amino-
substituted biaryls. Similar to amino-substituted biaryls, they are of
considerable pharmacological relevance and occur in a variety of
natural products. For example, sanguinarinone shows anti-pro-
liferative activity against leukemia HL-60 cells, antiparasitic activ-
ity, and anticoagulant activity.9 Anti-proliferative activity against
P-388 and human colon carcinoma HT-29 cells have been reported
for oxotoddaline.10 Oxynitidine possesses cytotoxic activity.11 Sev-
eral other biologically active natural products, such as narciprimine,
O
O
OH
O
O
Me
H
O
O
N
N
OH
O
O
Sanguinarinone
Narciprimine
The synthesis of nitro- and amino-substituted arenes and biar-
yls by nitration13 of arenes and biphenyls suffers from the low
regioselectivity. The classical synthesis of parent p-nitrophenol
relies on the nitration of phenol with nitric acid and subsequent
steam distillation (15% yield). The competing formation of
o-nitrophenol is a severe problem.14 Various studies to increase the
yield of pure 4-nitrophenol and related derivatives have been car-
ried out.15 Recently, p-nitrophenol has been prepared in 80% yield
by nitration of phenol with Fe(NO3)3$9H2O in the ionic liquid
[bbim][BF4].16 An additional problem arises from the fact that, due
to the harsh reaction conditions, several side-reactions are possible
for more complex substrates. Nitro-substituted biaryls are available
by Ullmann-type reactions and by nucleophilic aromatic sub-
stitutions.17 However, the scope of these reactions is limited by
steric and electronic effects (low conversion, formation of regio-
isomeric mixtures). The synthesis of amino-substituted biaryls by
* Corresponding author. Fax: þ49 381 4986412.
E-mail address: peter.langer@uni-rostock.de (P. Langer).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.09.014

A. Riahi et al. / Tetrahedron 65 (2009) 9300–9315
9301
palladium(0)-catalyzed coupling reactions18 suffers from the fact
that electron-rich arenes, in particular sterically encumbered sub-
strates, often react sluggishly or not at all. Last but not the least, the
synthesis of the required starting materials, highly functionalized
or sterically encumbered aryl halides or triflates (the latter derived
from the corresponding phenols), can be a difficult and tedious
task. 6(5H)-Phenanthridinones have been prepared from 2-alkoxy-
carbonyl-2-nitrobiaryls by reduction of the nitro into an amino
group (using Fe/AcOH, Fe/THF, Zn/HOAc, Raney-Ni, or H2-Pd/C) and
subsequent cyclization.19 Whereas this process is straightforward,
problems are, as described above, associated to the synthesis of
functionalized biaryl systems.
All syntheses of nitro- and amino-substituted arenes and biaryls,
which were outlined above, rely on the functionalization of a suit-
able arene. An interesting alternative is based on the use of synthetic
building blocks in cyclocondensation reactions. Davies et al. repor-
ted the regioselective synthesis of anilines by addition of ketones to
vinamidinium salts.20 Carter and co-workers reported the synthesis
of nitro-substituted biaryls based on Diels–Alder reactions.21 Chan
and co-workers were the first to report22 a convenient synthesis of
functionalized phenols by TiCl4-mediated [3þ3] cyclization23 of 1,3-
bis(trimethylsilyloxy)-1,3-butadienes24 with 3-silyloxy-2-en-1-
ones. Recently, we have reported25 the application of this reaction to
the synthesis of nitro- and amino-substituted biaryls and of 6(5H)-
phenanthridinones. We have also reported the synthesis of 4-nitro-
and 4-aminophenols based on formal [3þ3] cyclizations of
1,3-bis(trimethylsilyloxy)-1,3-butadienes with 3-ethoxy-2-nitro-2-
en-1-ones.26 Herein, we report full details of both studies. All
products reported herein are not readily available by other methods.
The TiCl4-mediated cyclization of 4a with 1,3-bis(trimethyl-
silyloxy)-1,3-butadiene 5a, prepared in two steps from methyl
3-oxopentanoate,22 afforded the nitro-substituted biaryl 6a. The for-
mation of the product can be explained by themechanism depicted in
Scheme 2. During optimization, it proved to be important to carry out
the reactions in a highly concentrated solution. We have observed
earlier that employment of other Lewis acids results in a decrease of
the yield of [3þ3] cyclocondensation reactions. It is important to be
noted that the cyclization proceeded with very good regioselectivity.
Me3SiO
OSiMe3
OMe
O
OH
O
OSiMe3
Ar
OMe
5a
Me
Me
Ar
i
4a
6a
Ar = 2-(NO2)C6H4
_
TiCl3OH
O
_
Cl4Ti
O
SiMe3
Ar
O
O
OMe
OTiCl3
+
Me
Me
Ar
A
E
4a
Me3SiCl
Me3SiO
O
O
Me3SiO
Me
OMe
OMe
Ar
Ar
OSiMe3
O
TiCl4
+
Me
OTiCl3
2. Results and discussion
Me3Si
_
Cl
D
B
The novel nitro-substituted benzoylacetones 3a–e,g,h were
prepared in 34–85% yields by LDA-mediated reaction of ketones
1a–e with benzoyl chlorides 2a–c (Scheme 1, Table 1). The reaction
of 3c with N-chlorosuccinimide (NCS) gave the chlorinated ben-
zoylacetone 3f. The silylation of 3a–h afforded the 1-aryl-1-silyl-
oxy-1-en-3-ones 4a–h in high yields.
O
Me3SiO
Me
OMe
(Me3Si)2O
TiCl4
TiCl4
Ar
OSiMe3
OSiMe3
C
O
O
OH
O
Scheme 2. Possible mechanism of the formation of 6a; i: TiCl4, CH2Cl2, ꢁ78/20 ꢀC,
R2
Cl
i
R2
R1
18 h.
+
R3
R5
R3
R5
R1
R4
2a-c
R4
The TiCl4-mediated cyclization of 4a–f with 1,3-bis(trimethyl-
silyloxy)-1,3-butadienes 5a–f, readily available in two steps from the
3a-h
1a-f
corresponding b
-ketoesters,22 afforded the nitro-substituted biaryls
ii
OSiMe3
O
6a–s (Scheme 3, Table 2). All cyclizations proceeded with very good
regioselectivity. The moderate yields can be explained by competing,
TiCl4-mediated oxidative dimerization of the 1,3-bis(silyloxy)-1,3-
R2
R1
R3
R5
R4
4a-h
Me3SiO OSiMe3
R2
Scheme 1. Synthesis of 3a–h and 4a–h; i: LDA (1.5 equiv), THF; ii: 1) NEt3 (1.6 equiv),
Me3SiCl (1.8 equiv), C6H6, 20 ꢀC, 3 d. Products 4 exist as mixtures of E/Z isomers.
O
OH
OR1
R2
R3
5a-f
OR1
i
OSiMe3
O
Table 1
Synthesis of 3a–h and 4a–h
R4
R3
O2N
R4
O2N
3,4
R1
R2
R3
R4
R5
% (3)a
% (4)a
6a-s
a
b
c
d
e
f
H
H
H
H
Me
Cl
H
Me
Et
nPr
nBu
Et
nPr
Me
Me
NO2
NO2
NO2
NO2
NO2
NO2
H
H
H
H
H
H
H
NO2
H
H
H
H
H
H
H
H
NO2
54
45
45
40
48
85b
34
43
91
95
88
93
94
92
90
92
4a-f
ii
OH
R4
O
R2
R3
H
N
g
h
H
H
7a-s
a
Yields of isolated products.
b
3f was prepared by chlorination of 3c, conditions: NCS (1.0 equiv), CCl4, 8 h, 75–
80 ꢀC.
Scheme 3. Synthesis of 6a–s and 7a–s; i: TiCl4, CH2Cl2, ꢁ78/20 ꢀC, 18 h ii: H2, Pd/C
(10 mol %), 20 ꢀC, 48 h.

9302
A. Riahi et al. / Tetrahedron 65 (2009) 9300–9315
Table 2
Synthesis of 6a–s and 7a–s
Me3SiO OSiMe3
R2
OR1
OSiMe3
O
OH
4
5
6,7
R1
R2
R3
R4
% (6)a
% (7)a
R2
5a-c
OR1
i
a
a
a
a
b
b
b
b
b
b
c
c
c
c
d
d
d
e
f
a
b
c
a
b
c
d
e
f
g
h
i
j
k
l
m
n
o
p
q
r
Me
Me
Et
Me
Me
Me
Et
Me
Me
Me
Me
Me
Et
Me
Me
Me
Me
Me
Me
H
Me
Et
nOct
H
Me
Et
nHex
nHept
nOct
H
Me
Et
nHex
H
Me
nHex
nHex
H
Me
Me
Me
Me
Et
Et
Et
Et
Et
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Me
Cl
36
41
35
40
43
42
38
41
39
38
48
38
37
25
42
39
38
38
55
64
52
70
69
75
53
52
51
49
50
56
50
63
74
70
54
50
50
49
O
Me
Me
f
NO2
NO2
6v-x
4h
a
b
c
d
e
f
a
b
c
d
a
b
d
d
a
Scheme 5. Synthesis of 6v–x; i: TiCl4, CH2Cl2, ꢁ78/20 ꢀC, 18 h ii: H2, Pd/C (10 mol %),
20 ꢀC, 48 h.
Et
nPr
nPr
nPr
nPr
nBu
nBu
nBu
Et
Table 4
Synthesis of 6v–x
5
6
R1
R2
% (6)a
a
b
c
v
w
x
Me
Me
Et
H
Me
Et
36
46
33
a
Yields of isolated products.
s
nPr
a
Yields of isolated products.
O
O
butadiene and by partial hydrolysis of the starting materials during
the reaction. No clear trend is observed for the yield with respect to
the influence of the substitution pattern. The Pd/C-catalyzed hydro-
genation of 6a–s directly afforded the 6(5H)-phenanthridinones 7a–s
in good yields (Scheme 3, Table 2). The configuration of all products
was established by spectroscopic methods.
The TiCl4-mediated cyclization of 4g with 1,3-bis(trimethyl-
silyloxy)-1,3-butadienes 5b,c afforded the 3-nitro-30-hydroxy-
biaryls 6t,u (Scheme 4, Table 3). The hydrogenation of 6t and 6u
afforded the 3-amino-30-hydroxy-biphenyls 8a and 8b.
i
Cl
Ar
Ar
PhO
Ar
9a-c
10a-c
ii
O
O
O2N
iii
O2N
Ar
OEt
12a-c
11a-c
Scheme 6. Synthesis of 12a–c; i: PhOH (1.0 equiv), 9a–c (1.03 equiv), 60 ꢀC; ii: CH3NO2
(1.0 equiv), 10a–c (0.33 equiv), t-BuOK (1.0 equiv), urea (equiv) DMSO, 12 h, 0–10 ꢀC;
iii: 11a–c (1.0 equiv), Ac2O (1.0 equiv), HC(OEt)3 (1.2 equiv), 120 ꢀC, 6 h.
Me3SiO OSiMe3
O
OH
R2
R2
OR1
OR1
NO2
5b,c
i
Me
OSiMe3
O
Me3SiO
R2
OSiMe3
R1
Me
O
OH
6t,u
R2
O
O
R1
5
4g
i
ii
NO2
+
O
Ar
O
OH
O2N
NO2
R2
Ar
OR1
13a-i
OEt
12a-c
Me
ii
O
OH
NH2
8a,b
R2
O
R1
Scheme 4. Synthesis of 6t,u and 8a,b; i: TiCl4, CH2Cl2, ꢁ78/20 ꢀC, 18 h ii: H2, Pd/C
(10 mol %), 20 ꢀC, 48 h.
Ar
NH2
14a-i
Table 3
Synthesis of 6t,u and 8a,b
Scheme 7. Synthesis of 14a–i; i: TiCl4, CH2Cl2, ꢁ78/20 ꢀC, 18 h, ii: H2, Pd/C (10 mol %),
R1
R2
% (6)a
% (8)a
20 ꢀC, 48 h.
5
6
8
b
c
t
u
a
b
Me
Et
Me
Et
50
37
81
78
Table 5
Synthesis of 14a–i
a
Yields of isolated products.
12
5
13,14
Ar
R1
R2
% (13)a
% (14)a
The TiCl4-mediated cyclization of 4h with 1,3-bis
a
a
a
a
a
b
b
c
a
b
c
k
f
a
b
a
b
a
b
c
d
e
f
g
h
i
Ph
Ph
Ph
Ph
Me
Me
Et
Me
Me
Me
Me
Me
Me
H
Me
Et
nBu
nOct
H
Me
H
56
57
65
58
62
68
72
56
70
86
85
95
92
90
91
89
88
90
(trimethylsilyloxy)-1,3-butadienes 5a–c afforded the 4-nitro-30-
hydroxy-biaryls 6v–x (Scheme 5, Table 4).
Aryl phenolates 12a–c were prepared from aroyl chlorides 9a–c
Ph
according to the literature.27 The reaction of 10a–c with nitrometh-
2-MeC6H4
2-MeC6H4
2-ClC6H4
2-ClC6H4
ane, following a known procedure,28 gave the
a-nitroacetophenones
11a–c (Scheme 6). The reaction of the latter with triethyl ortho-
formate and acetic anhydride afforded the 3-ethoxy-2-nitro-2-en-1-
ones 12a–c.
c
Me
a
Yields of isolated products.

A. Riahi et al. / Tetrahedron 65 (2009) 9300–9315
9303
The TiCl4-mediated cyclization of 3-ethoxy-2-nitro-2-en-1-ones
12a–c with 1,3-bis(trimethylsilyloxy)-1,3-butadienes 5a–c,k,f affor-
ded the 4-nitrophenols 13a–i in 56–72% yield (Scheme 7, Table 5).
The yields of the products derived from dienes 5b,c,k,f, containing
a substituent located at carbon atom C-4 of the diene, were higher
than those derived from 5a. The hydrogenation of 4-nitrophenols
13a–i, in the presence of catalytic amounts of Pd/C (10 mol %),
afforded the 4-aminophenols 14a–i in excellent yields.
124.4,129.1,130.8,132.8 (CHAr),134.2,148.1 (CAr),186.6 (COH),194.5
(CO). MS (EI 70 eV): m/z (%)¼221 ([M]þ, 2), 151 (11), 150 (100), 136
(24), 135 (24), 134 (11), 104 (16), 92 (17), 79 (10), 77 (14), 76 (18), 57
(43), 51 (16), 43 (300). HRMS (EI): Calcd for C11H11O4N: 221.06826;
found: 221.068437.
4.2.3. 1-Hydroxy-1-(2-nitrophenyl)hex-1-en-3-one (3c). Starting with
LDA (1.5 equiv) in THF (62 mL), 1c (5.3 mL, 50.0 mmol), and 2a
(7.9 mL, 60.0 mmol), 3c was isolated as a yellowish oil (5.98 g, 46%).
3. Conclusions
1H NMR (250 MHz, CDCl3):
d
¼1.12 (t, 3J¼7.6 Hz, 3H, CH2CH2CH3),
1.40–1.45 (m, 2H, CH2CH2CH3), 2.40 (t, 3J¼7.4 Hz, 2H, CH2CH2CH3),
In conclusion, we have reported a regioselective approach to
functionalized nitro- and amino-substituted biaryls and of 6(5H)-
phenanthridinones by [3þ3]cyclocondensation of 1,3-bis-
(trimethylsilyloxy)-1,3-butadienes with nitro-substituted 1-aryl-1-
silyloxy-1-en-3-ones and subsequent hydrogenation. We have also
reported the synthesis of 4-nitro- and 4-aminophenols based on
formal [3þ3] cyclizations of 1,3-bis(trimethylsilyloxy)-1,3-butadi-
enes with 3-ethoxy-2-nitro-2-en-1-ones. The products are not
readily available by other methods.
5.70 (s, 1H, CH), 7.46–7.56 (m, 3H, CHAr), 7.83–7.86 (m, 1H, CHAr),
15.12 (br s, 1H, OH). 13C NMR (75 MHz, CDCl3):
d¼13.5 (CH3), 18.5,
32.5 (CH2), 98.4 (CH), 124.4, 129.2, 130.9, 132.9 (CHAr), 134.1, 148.1
(CAr), 186.5 (COH), 194.6 (CO).
4.2.4. 1-Hydroxy-1-(2-nitrophenyl)hept-1-en-3-one (3d). Starting
with LDA (1.5 equiv) in THF (62 mL), 1d (6.2 mL, 50.0 mmol), and 2a
(7.9 mL, 60.0 mmol), 3d was isolated as a red to yellow oil (5.98 g,
40%). 1H NMR (250 MHz, CDCl3):
CH2CH2CH2CH3), 1.35–1.44 (m, 2H, CH2), 1.59–1.70 (m, 2H, CH2),
2.38 (t, 3J¼7.8 Hz, 2H, CH2CH2CH2CH3), 5.79 (s, 1H, CH), 7.54–7.64
(m, 3H, CHAr), 7.90–7.93 (m, 1H, CHAr), 15.24 (br s, 1H, OH). 13C NMR
d
¼0.95 (t, 3J¼7.4 Hz, 3H,
4. Experimental section
4.1. General comments
(75 MHz, CDCl3):
124.4, 129.1, 131.0, 132.8 (CHAr), 134.6, 147.8 (CAr), 186.9 (COH), 193.2
(CO).
d
¼13.7 (CH3), 22.2, 27.8, 37.5 (CH2), 99.1 (CH),
All solvents were dried by standard methods and all reactions
were carried out under an Argon atmosphere. For 1H and 13C NMR
spectra the deuterated solvents indicated were used. Mass spec-
trometric data (MS) were obtained by electron ionization (EI,
70 eV), chemical ionization (CI, isobutane) or electrospray ioniza-
tion (ESI). For preparative scale chromatography silica gel 60
(0.063–0.200 mm, 70–230 mesh) was used.
4.2.5. 2-Methyl-1-(2-nitrophenyl)pentane-1,3-dione (3e). Starting
with LDA (1.5 equiv) in THF (24 mL), 1e (2.1 mL, 20.0 mmol), and
2a (3.2 mL, 24.0 mmol), 3e was isolated as a red to yellow oil
(2.70 g, 48%). 1H NMR (250 MHz, CDCl3):
d
¼1.12 (t, 3J¼7.0 Hz, 3H,
CH2CH3), 1.41 (d, 3J¼6.7 Hz, 3H, CH3CHCOC2H5), 2.46 (q,
3J¼7.3 Hz, 2H, CH2CH3), 4.04 (q, 3J¼7.1 Hz, 1H, CHCH3), 7.34–7.67
(m, 3H, CHAr), 8.05–8.08 (m, 1H, CHAr). 13C NMR (75 MHz, CDCl3):
4.2. General procedure for the synthesis of 1,3-dicarbonyl
compounds 3a–h
d
¼7.5, 13.6 (CH3), 34.9 (CH2), 60.0 (CH), 124.3, 128.4, 130.6, 134.6
(CHAr), 137.0, 145.4 (CAr), 196.3, 207.6 (CO). MS (EI 70 eV): m/z
(%)¼235 ([M]þ, 2), 151 (10), 150 (78), 136 (15), 135 (13), 104 (13),
92 (12), 79 (13), 77 (16), 76 (31), 57 (100), 51 (22), 50 (14), 43 (9),
29 (25). HRMS (EI): Calcd for C12H13NO4: 235.08391; found:
235.083664.
To a stirred solution of LDA (75.0 mmol) in THF (1.2 mL/
1.0 mmol of LDA) was added ketone 1a–e (50.0 mmol) at ꢁ78 ꢀC.
After stirring of the solution for 1 h, 2a–c (60.0 mmol) was added.
The temperature of the solution was allowed to rise to 20 ꢀC during
12 h. A saturated aqueous solution of NH4Cl was added, the layers
were separated, and the aqueous layer was extracted with EtOAc
(3ꢂ50 mL). The combined organic layers were dried (Na2SO4)
and filtered, and the solvent was removed in vacuo. The residue was
purified by chromatography (silica gel, n-heptane/EtOAc ¼ 30:1
/20:1) to give 3. Compounds 1a–e and 2a–c are commercially
available.
4.2.6. 2-Chloro-1-(2-nitrophenyl)hexane-1,3-dione (3f). A mixture
of 3c (2.00 g, 8.5 mmol) and of NCS (1.04 g, 7.8 mmol) in CCl4
(18 mL) was heated under reflux for 8 h. After cooling, the pre-
cipitate of succinimide was filtered off and water was added, the
layers were separated, and the aqueous layer was extracted with
CH2Cl2 (3ꢂ150 mL). The combined organic layers were dried
(Na2SO4) and filtered, and the solvent was removed in vacuo. The
residue was purified by chromatography (silica gel, n-heptane/
EtOAc, 30:1/20:1) to give 3f as a yellowish oil (1.95 g, 85%). 1H
4.2.1. 4-Hydroxy-4-(2-nitrophenyl)but-3-en-2-one (3a). Starting with
LDA (1.5 equiv) in THF (62 mL), 1a (2.9 mL, 50.0 mmol), and 2a
(7.9 mL, 60.0 mmol), 3a was isolated as a red to yellow oil (5.405 g,
NMR (CDCl3, 250 MHz):
d
¼0.96 (t, 3J¼7.1 Hz, 3H, CH2CH2CH3),
54%). 1H NMR (250 MHz, CDCl3):
d
¼2.19 (s, 3H, CH3), 6.16 (s, 1H,
CH), 7.45–7.60 (m, 3H, CHAr), 7.82 (m, 1H, CHAr), 15.12 (s, 1H, OH).
13C NMR (75 MHz, CDCl3):
1.61–1.73 (m, 2H, CH2CH2CH3), 2.55 (t, 3J¼7.4 Hz, 2H, CH2CH2CH3),
5.23 (s, 1H, CH), 7.53–7.78 (m, 3H, CHAr), 8.23–8.27 (m, 1H, CHAr).
d
¼24.2 (CH3), 99.9 (CH), 124.3, 129.3,
13C NMR (CDCl3, 75 MHz):
d
¼13.7 (CH3), 18.6, 37.3 (CH2), 69.6
130.0, 133.0 (CHAr), 134.7, 147.8, (CAr), 187.1 (COH), 190.2 (C]O).
MS (EI 70 eV): m/z (%)¼207 ([M]þ, 38), 192 (100), 160 (19), 150
(36), 120 (8), 89 (9), 85 (27), 76 (18), 43 (45). HRMS (EI): Calcd for
C10H9O4N: 207.05261; found: 207.05232.
(CH), 124.4, 130.0, 131.7, 134.9 (CHAr), 139.5, 145.4 (CAr), 189.5,
199.8 (CO).
4.2.7. 4-Hydroxy-4-(4-nitrophenyl)but-3-en-2-one (3h). Starting with
LDA (1.5 equiv) in THF (62 mL), 1a (2.9 mL, 50.0 mmol), and 2c
(11.130 g, 60.0 mmol), 3h was isolated as a yellow solid (4.405 g, 43%),
4.2.2. 1-Hydroxy-1-(2-nitrophenyl)pent-1-en-3-one (3b). Starting
with LDA (1.5 equiv) in THF (62 mL), 1b (4.5 mL, 50.0 mmol), and 2a
(7.9 mL, 60.0 mmol), 3b was isolated as a yellowish solid (11.93 g,
mp¼54–56 ꢀC.1H NMR (300 MHz, CDCl3):
¼2.11 (s, 3H, CH3), 5.74 (s,
d
1H, CH), 7.95 (d, 3J¼8.7 Hz, 2H, CHAr), 8.21 (d, 3J¼9.0 Hz, 2H, CHAr),
45%), mp¼58–60 ꢀC. 1H NMR (250 MHz, CDCl3):
d
¼1.10 (t,
15.80 (s, 1H, OH). 13C NMR (75 MHz, CDCl3):
124.3 (2CHAr), 128.6 (2CHAr), 140.9, 149.9 (CAr), 179.8 (COH), 196.6
(C]O). GC–MS (EI 70 eV): m/z (%)¼207 ([M]þ, 38),192 (100), 165 (8),
160 (19), 150 (36), 120 (8), 104 (18), 89 (9), 85 (27), 76 (18), 63 (7), 50
d
¼27.0 (CH3), 98.5 (CH),
3J¼7.7 Hz, 3H, CH2CH3), 2.58 (q, 3J¼7.1 Hz, 2H, CH2CH3), 5.73 (s, 1H,
CH), 7.45–7.55 (m, 3H, CHAr), 7.80–7.83 (m, 1H, CHAr), 15.10 (br s, 1H,
OH).13C NMR (75 MHz, CDCl3):
d¼9.6 (CH3), 31.5 (CH2), 98.5 (CH),

9304
A. Riahi et al. / Tetrahedron 65 (2009) 9300–9315
(12), 43 (45). HRMS (EI): Calcd for C10H9NO4: 207.05261; found:
207.05232.
CH2CH3), 7.28–7.54 (m, 3H, CHAr), 8.00–8.03 (m, 1H, CHAr). 13C NMR
(75 MHz, CDCl3):
(C), 123.6, 128.9, 130.5, 132.6 (CHAr), 145.6, 152.9 (CAr), 168.5 (C–
OSiMe3), 202.8 (CO).
d
¼0.2 (Si(CH3)3), 7.1, 12.5 (CH3), 34.0 (CH2), 118.2
4.3. General procedure for the synthesis of silyl enol ethers
4a–h and 10
4.3.6. 2-Chloro-1-(2-nitrophenyl)-1-(trimethylsilyloxy)hex-1-en-3-
one (4f). Starting with benzene (52.0 mL), 3f (1.95 g, 7.22 mmol),
triethylamine (1.6 mL, 11.6 mmol) and trimethylchlorosilane
(1.6 mL, 13.0 mmol), 4f was isolated as a yellowish oil (2.27 g, 92%).
To a stirred benzene solution (2.5 mL/1.0 mmol of 3 or 9) of 3 or
9 (10.0 mmol) was added triethylamine (16.0 mmol). After stirring
of the solution for 2 h, trimethylchlorosilane (18.0 mmol) was
added. After stirring of the solution for 72 h, the solvent was re-
moved in vacuo and hexane (25 mL) was added to the residue to
give a suspension. The latter was filtered under argon atmosphere.
The filtrate was concentrated in vacuo to give silyl enol ethers 4a–h
or 10. Due to the unstable nature of the silyl enol ethers, they were
characterized only by NMR spectroscopy. All products exist as
mixtures of E/Z isomers.
1H NMR (250 MHz, CDCl3):
d
¼0.10–0.23 (m, 9H, Si(CH3)3), 0.93 (t,
3J¼7.4 Hz, 3H, CH2CH2CH3), 1.58–1.69 (m, 2H, CH2), 2.53 (t,
3J¼7.6 Hz, 2H, CH2CH2CH3), 7.42–7.63 (m, 3H, CHAr), 8.13–8.23 (m,
1H, CHAr). 13C NMR (75 MHz, CDCl3):
d
¼0.1 (Si(CH3)3), 13.4 (CH3),
18.2, 37.0 (CH2), 108.9 (CCl), 124.2, 129.9, 131.2, 132.8 (CHAr), 143.2,
147.6 (CAr), 165.1 (C–OSiMe3), 189.1 (CO).
4.3.7. 4-(4-Nitrophenyl)-4-(trimethylsilyloxy)but-3-en-2-one
(4h). Starting with benzene (52.0 mL), 3h (4.405 g, 21.3 mmol),
triethylamine (4.7 mL, 33.0 mmol) and trimethylchlorosilane
(5.1 mL, 37.8 mmol), 4h was isolated as a yellow solid (5.350 g,
4.3.1. 4-(2-Nitrophenyl)-4-(trimethylsilyloxy)but-3-en-2-one
(4a). Starting with benzene (90.0 mL), 3a (6.121 g, 29.5 mmol),
triethylamine (6.6 mL, 47.2 mmol) and trimethylchlorosilane
(6.7 mL, 53.2 mmol), 4a was isolated as a reddish oil (7.30 g, 91%).1H
92%), mp¼55–57 ꢀC. 1H NMR (300 MHz, CDCl3):
¼0.02–0.22 (m,
d
NMR (300 MHz, CDCl3):
CH3), 6.06 (s,1H, CH), 7.45–7.60 (m, 3H, CHAr), 7.82 (m,1H, CHAr), 13
NMR (75 MHz, CDCl3):
d
¼0.05–0.30 (m, 9H, Si(CH3)3), 2.15 (s, 3H,
9H, Si(CH3)3), 2.10 (s, 3H, CH3), 6.08 (s, 1H, CH), 7.80–7.89 (m, 2H,
C
CHAr), 8.09–8.17 (m, 2H, CHAr). 13C NMR (75 MHz, CDCl3):
(Si(CH3)3), 24.6 (CH3), 96.8 (CH), 121.5 (2CHAr), 125.9 (2CHAr), 138.4,
d
¼0.6
d
¼0.2 (Si(CH3)3), 24.5 (CH3), 98.9 (CH),124.9,
129.6, 130.5, 133.5 (CHAr),134.9, 148.8, (CAr),180.1 (C–OSiMe3),191.2
147.0 (CAr), 177.2 (C–OSiMe3), 194.1 (C]O).
(C]O).
4.4. General procedure for the synthesis of salicylates 6a–x
4.3.2. 1-(2-Nitrophenyl)-1-(trimethylsilyloxy)pent-1-en-3-one
(4b). Starting with benzene (52.0 mL), 3b (4.62 g, 20.9 mmol), tri-
ethylamine (4.6 mL, 33.4 mmol) and trimethylchlorosilane (4.7 mL,
37.6 mmol), 4b was isolated as a reddish oil (5.80 g, 95%). 1H NMR
To a CH2Cl2 solution of silyl enol ether 4 (1.0 equiv) and 1,3-bis-
(silyl enol ether) 5 (1.1 equiv) was dropwise added TiCl4 (1.1 equiv) at
ꢁ78 ꢀC under argon atmosphere. The solution was stirred at ꢁ78 ꢀC
for 30 min and then allowed to warm to 20 ꢀC during 18 h. To the
solution was added an aqueous solution of HCl (10%). The organic
layer was separated and the aqueous layer was repeatedly extracted
with CH2Cl2. The combined organic extracts were dried (Na2SO4) and
filtered. The filtrate was concentrated in vacuo and the residue was
purified by chromatography (silica gel, n-hexane/EtOAc) to give
salicylates 6.
(250 MHz, CDCl3):
d
¼0.21–0.31 (m, 9H, Si(CH3)3), 0.98 (t, 3J¼7.6 Hz,
3H, CH2CH3), 2.58 (q, 3J¼7.1 Hz, 2H, CH2CH3), 5.81 (s, 1H, CH), 7.44–
7.53 (m, 3H, CHAr), 7.80–7.83 (m,1H, CHAr).13C NMR (75 MHz, CDCl3):
d
¼0.3 (Si(CH3)3), 7.8 (CH3), 36.8 (CH2), 98.4 (CH), 123.6, 127.9, 129.4,
131.9 (CHAr), 134.6, 145.0 (CAr), 177.4 (C–OSiMe3), 198.5 (CO).
4.3.3. 1-(2-Nitrophenyl)-1-(trimethylsilyloxy)hex-1-en-3-one
(4c). Starting with benzene (63.0 mL), 3c (4.83 g, 20.2 mmol),
triethylamine (4.5 mL, 43.0 mmol) and trimethylchlorosilane
(4.6 mL, 33.1 mmol), 4c was isolated as a reddish oil (5.60 g, 88%).
4.4.1. Methyl 3-hydroxy-5-methyl-20-nitro[1,10-biphenyl]-2-carboxy-
late (6a). Starting with 5a (1.145 g, 4.4 mmol), TiCl4 (0.835 g,
4.4 mmol), CH2Cl2 (6 mL) and 4a (1.117 g, 4.0 mmol), 6a was isolated
1H NMR (250 MHz, CDCl3):
d
¼0.21–0.43 (m, 9H, Si(CH3)3), 1.06–1.14
(m, 3H, CH3),1.69–1.85 (m, 2H, CH2), 2.43–2.53 (m, 2H, CH2), 5.85 (s,
(0.420 g, 36%) as a yellowish oil. 1H NMR (CDCl3, 250 MHz):
d¼2.21
1H, CH), 7.50–8.00 (m, 3H, CHAr), 8.07–8.19 (m, 1H, CHAr), 13C NMR
(s, 3H, CH3), 3.33 (s, 3H, OCH3), 6.35 (d, 4J¼1.9 Hz, 1H, CHAr), 6.74 (d,
4J¼1.4 Hz, 1H, CHAr), 7.10–7.13 (m, 1H, CHAr), 7.36 (ddd, 3J¼7.4 Hz,
3J¼7.2 Hz, 4J¼1.4 Hz, 1H, CHAr), 7.47 (ddd, 3J¼7.5 Hz, 3J¼7.4 Hz,
4J¼1.5 Hz, 1H, CHAr), 7.92 (dd, 3J¼8.0 Hz, 4J¼1.5 Hz, 1H, Ar), 11.10 (s,
1H, OH).13C NMR (CDCl3, 75 MHz): dC¼21.6 (CH3), 51.9 (OCH3),108.4
(CAr),118.0,122.5,123.6,127.8,131.1.132.4 (CHAr),138.2,140.2,145.6,
147.8, 162.4 (CAr), 170.4 (C]O). GC–MS (EI, 70 eV): m/z (%)¼287
([M]þ, 26), 255 (100), 227 (27), 197 (5), 181 (11), 152 (30), 115 (5), 76
(7). HRMS (EI): Calcd for C15H13NO5: 287.07882; found: 287.07873.
(75 MHz, CDCl3):
(CH), 124.1, 128.1, 129.3, 131.6 (CHAr), 139.4, 148.3, (CAr), 178.0 (C–
d
¼0.2 (Si(CH3)3), 13.8 (CH3), 36.4, 39.5 (CH2), 98.9
OSiMe3), 193.2 (C]O).
4.3.4. 1-(2-Nitrophenyl)-1-(trimethylsilyloxy)hept-1-en-3-one
(4d). Starting with benzene (22.5 mL), 3d (2.20 g, 8.9 mmol), tri-
ethylamine (2.0 mL, 14.2 mmol) and trimethylchlorosilane (2.0 mL,
16.0 mmol), 4d was isolated as a reddish oil (2.66 g, 93%). 1H NMR
(250 MHz, CDCl3):
d
¼0.24–0.27 (m, 9H, Si(CH3)3), 0.89 (t, 3J¼7.6 Hz,
3H, CH2CH2CH2CH3), 1.31–1.38 (m, 2H, CH2), 1.51–1.60 (m, 2H, CH2),
2.34 (t, 3J¼6.8 Hz, 2H, CH2CH2CH2CH3), 5.79 (s, 1H, CH), 7.53–7.65
(m, 3H, CHAr), 7.91–7.94 (m, 1H, CHAr). 13C NMR (75 MHz, CDCl3):
4.4.2. Methyl 3-hydroxy-4,5-dimethyl-20-nitrobiphenyl-2-carboxy-
late (6b). Starting with 5b (1.207 g, 4.4 mmol), TiCl4 (0.834 g,
4.4 mmol), CH2Cl2 (8 mL), and 4a (1.117 g, 4.0 mmol), 6b was iso-
lated (0.500 g, 41%) as a yellow oil. 1H NMR (CDCl3, 250 MHz):
d
¼0.3 (Si(CH3)3), 13.6 (CH3), 22.1, 27.7, 37.4 (CH2), 99.0 (CH), 124.1,
129.0, 131.1, 132.8 (CHAr), 133.4, 139.1 (CAr), 176.5 (C–OSiMe3), 193.3
(CO).
d
¼2.10 (s, 3H, CH3), 2.16 (s, 3H, CH3), 3.32 (s, 3H, OCH3), 6.35 (s, 1H,
CHAr), 7.11 (dd, 3J¼7.5 Hz, 4J¼1.6 Hz, 1H, CHAr), 7.33 (ddd, 3J¼7.7 Hz,
3J¼7.6 Hz, 4J¼1.5 Hz, 1H, CHAr), 7.46 (ddd, 3J¼7.6 Hz, 3J¼7.5 Hz,
4J¼1.3 Hz, 1H, CHAr), 7.88 (dd, 3J¼8.3 Hz, 4J¼1.4 Hz, 1H, CHAr), 11.47
(s, 1H, OH). 13C NMR (CDCl3, 75 MHz): dC¼11.5, 20.5 (CH3), 51.9
(OCH3), 108.0 (CAr), 122.6, 123.5, (CHAr), 125.0 (CAr), 127.6, 131.2,
132.3 (CHAr), 136.9, 138.5, 143.6, 148.0, 160.5 (CAr), 171.4 (C]O). GC–
MS (EI, 70 eV): m/z (%)¼301 ([M]þ, 64), 269 (100), 255 (24), 224
(27), 208 (48), 195 (13), 180 (49), 165 (29), 152 (28), 128 (11), 115
4.3.5. 2-Methyl-1-(2-nitrophenyl)-1-(trimethylsilyloxy)pent-1-en-3-
one (4e). Starting with benzene (29.0 mL), 3e (2.70 g, 11.5 mmol),
triethylamine (2.6 mL, 18.4 mmol) and trimethylchlorosilane
(2.6 mL, 20.7 mmol), 4e was isolated as a yellowish oil (3.31 g, 94%).
1H NMR (250 MHz, CDCl3):
d
¼0.1–0.29 (m, 9H, Si(CH3)3), 0.88 (t,
3J¼6.8 Hz, 3H, CH2CH3), 2.02 (s, 3H, CH3), 2.36 (q, 3J¼8.7 Hz, 2H,

A. Riahi et al. / Tetrahedron 65 (2009) 9300–9315
9305
(16), 77 (7). HRMS (EI): Calcd for C16H15NO5: 301.09447; found:
301.09434.
CHAr), 7.46 (ddd, 3J¼7.3 Hz, 3J¼7.3 Hz, 4J¼1.6 Hz, 1H, CHAr), 7.90 (dd,
3J¼8.3 Hz, 4J¼1.4 Hz, 1H, CHAr), 11.48 (s, 1H, OH). 13C NMR (CDCl3,
75 MHz):
d¼11.0, 14.1 (CH3), 27.0 (CH2), 51.9 (OCH3), 108.0
4.4.3. Ethyl 4-ethyl-3-hydroxy-5-methyl-20-nitrobiphenyl-2-carboxy-
late (6c). Starting with 5c (0.998 g, 3.3 mmol), TiCl4 (0.625 g,
3.3 mmol), CH2Cl2 (6 mL), and 4a (0.789 g, 3.0 mmol), 6c was iso-
lated (0.350 g, 35%) as a yellow solid, mp¼80–82 ꢀC. 1H NMR (CDCl3,
(CCOOCH3), 121.0, 123.5, 124.4, 127.6, 131.3, 132.6 (CHAr), 137.1, 138.7,
143.3, 149.2, 160.8 (CAr), 170.4 (CO). IR (neat, cmꢁ1):
~
n
¼3065 (w),
2967 (w), 2874 (w), 1659 (s), 1606 (m), 1567 (m), 1522 (s), 1437 (m),
1397 (m), 1345 (s), 1269 (s), 1214 (m), 1173 (m), 1144 (m), 1108 (w),
1044 (w), 927 (w), 867 (w), 809 (m), 730 (s), 683 (m), 632 (w), 605
(w). GC–MS (EI, 70 eV): m/z (%)¼315 ([M]þ, 59), 284 (19), 283 (100),
269 (21), 254 (12), 238 (28), 224 (22), 222 (20), 195 (10), 194 (38),
193 (10), 181 (10), 178 (10), 168 (10), 167 (16), 166 (12), 165 (32), 153
(10), 152 (20), 151 (9), 139 (10), 128 (9), 127 (8), 115 (12), 77 (8), 76
(7). HRMS (EI): Calcd for C17H17NO5: 315.11012; found: 315.110575.
250 MHz):
d
¼0.59 (t, 3J¼7.4 Hz, 3H, CH3), 1.04 (t, 3J¼7.5 Hz, 3H, CH3),
2.19 (s, 3H, CH3), 2.61 (m, 2H, CH2), 3.82 (q, 3J¼7.5 Hz, 2H, OCH2), 6.32
(s, 1H, CHAr), 7.12 (dd, 3J¼7.5 Hz, 4J¼1.5 Hz, 1H, CHAr), 7.34 (ddd,
3J¼8.0 Hz, 3J¼7.5 Hz, 4J¼1.5 Hz, 1H, CHAr), 7.45 (ddd, 3J¼7.5 Hz,
3J¼7.5 Hz, 4J¼1.5 Hz, 1H, CHAr), 7.88 (dd, 3J¼7.6 Hz, 4J¼1.6 Hz, 1H,
CHAr), 11.58 (s, 1H, OH). 13C NMR (CDCl3, 62 MHz): dC¼4.8, 14.8, 21.3
(CH3), 21.5 (CH2), 62.8 (OCH2), 110.0 (CAr), 124.6, 125.5, 129.4 (CHAr),
132.8 (CAr), 133.1, 134.1 (CHAr), 138.8, 140.8, 144.5, 149.9, 162.5 (CAr),
172.5 (C]O). GC–MS (EI, 70 eV): m/z (%)¼329 ([M]þ, 100), 283 (80),
255 (24), 238 (32), 222 (78), 207 (40),194 (99),165 (64),152 (29),139
(13), 115 (18), 77 (13). HRMS (EI): Calcd for C18H19NO5: 329.12577;
found: 329.12546.
4.4.7. Ethyl
4,5-diethyl-3-hydroxy-20-nitrobiphenyl-2-carboxylate
(6g). Starting with 5c (1.996 g, 6.6 mmol), TiCl4 (1.251 g, 6.6 mmol),
CH2Cl2 (12 mL) and 4b (1.760 g, 6.0 mmol), 6g was isolated (0.782 g,
38%) as a yellowish oil. 1H NMR (CDCl3, 250 MHz):
d
¼0.54–0.62 (m,
6H, 2ꢂCH2CH3), 1.10 (t, 3J¼6.9 Hz, 3H, OCH2CH3), 2.52 (q, J¼7.7 Hz,
2H, CH2CH3), 2.65 (q, 3J¼7.7 Hz, 2H, CH2CH3), 3.76 (q, 3J¼7.5 Hz, 2H,
OCH2CH3), 6.34 (s,1H, CHAr), 6.99 (dd, 3J¼7.4 Hz, 4J¼1.3 Hz,1H, CHAr),
7.34 (ddd, 3J¼7.3 Hz, 3J¼7.2 Hz, 4J¼1.4 Hz, 1H, CHAr), 7.42 (ddd,
3J¼7.5 Hz, 3J¼7.5 Hz, 4J¼1.5 Hz, 1H, CHAr), 7.94 (dd, 3J¼7.9 Hz,
4J¼1.4 Hz, 1H, CHAr), 11.43 (s, 1H, OH). 13C NMR (CDCl3, 62 MHz):
3
4.4.4. Methyl 3-hydroxy-5-methyl-20-nitro-4-octylbiphenyl-2-carboxy-
late (6d). Starting with 5f (1.100 g, 3.3 mmol), TiCl4 (0.625 g,
3.3 mmol), CH2Cl2 (6 mL) and 4a (0.789 g, 3.0 mmol), 6d was iso-
lated (0.476 g, 40%) as a yellow viscous oil. 1H NMR (CDCl3,
250 MHz):
d
¼0.73–0.79 (m, 3H, CH3), 1.13–1.30 (m, 12H, CH2), 2.18
d
¼13.3, 13.8, 17.2 (CH3), 19.0, 19.8 (CH2), 60.9 (OCH2), 108.0
(s, 3H, CH3), 2.52–2.60 (m, 2H, CH2), 3.31 (s, 3H, OCH3), 6.32 (s, 1H,
CHAr), 7.11 (dd, 3J¼7.5 Hz, 4J¼1.2 Hz, 1H, CHAr), 7.33 (ddd, 3J¼8.0 Hz,
3J¼7.7 Hz, 4J¼1.3 Hz, 1H, CHAr), 7.45 (ddd, 3J¼7.4 Hz, 3J¼7.1 Hz,
4J¼1.6 Hz, 1H, CHAr), 7.88 (dd, 3J¼7.5 Hz, 4J¼1.5 Hz, 1H, CHAr), 11.43
(s,1H, OH).13C NMR (CDCl3, 62 MHz): dC¼16.0, 21.8 (CH3), 24.6, 28.3,
30.6, 31.2, 31.4, 32.0, 33.8 (CH2), 53.8 (OCH3),110.0 (CAr),124.8,125.4,
129.5 (CHAr), 131.8 (CAr), 133.2, 134.1 (CHAr), 138.9, 140.5, 144.5,
150.0, 162.5 (CAr), 172.9 (C]O). GC–MS (EI, 70 eV): m/z (%)¼399
([M]þ,100), 353 (49), 340 (13), 306 (17), 268 (69), 225 (84), 208 (80),
194 (58), 180 (27), 165 (65), 152 (21), 115 (10), 77 (5), 43 (18). HRMS
(EI): Calcd for C23H29NO5: 399.20402; found: 399.20336.
(CCOOC2H5), 124.1, 123.8, 127.4, 131.2, 132.6 (CHAr), 125.8, 135.4,137.1,
142.6, 148.5, 158.4 (CAr),170.7 (CO). IR (neat, cmꢁ1):
¼3066 (w), 2965
~
n
(w), 2873 (w), 1656 (m), 1606 (m), 1563 (w), 1525 (s), 1463 (w), 1396
(m), 1347 (m), 1276 (s), 1212 (m), 1177 (m), 1111 (w), 1056 (w), 906
(w), 838 (s), 784 (m), 680 (m), 649 (w), 632 (w). GC–MS (EI, 70 eV):
m/z (%)¼344 ([M]þþ1, 25), 343 ([M]þ, 100), 298 (11), 297 (52), 280
(10), 270 (11), 269 (20), 253 (16), 252 (35), 250 (11), 238 (16), 237 (16),
235 (16), 234 (18), 224 (17), 222 (11), 221 (24), 220 (49), 218 (11), 210
(11), 208 (56), 207 (63), 206 (26),196 (11),194 (18),193 (25),192 (15),
181 (21), 180 (29), 178 (25), 168 (12), 167 (20), 166 (14), 165 (47), 153
(12), 152 (25), 151 (10), 139 (11), 128 (12), 115 (14), 77 (11), 29 (20).
HRMS (EI): Calcd for C19H21NO5: 343.14142; found: 343.141422.
4.4.5. Methyl 5-ethyl-3-hydroxy-20-nitrobiphenyl-2-carboxylate (6e).
Starting with 5a (1.720 g, 6.6 mmol), TiCl4 (1.251 g, 6.6 mmol),
CH2Cl2 (12 mL) and 4b (1.760 g, 6.0 mmol), 6e was isolated (0.780 g,
4.4.8. Methyl 5-ethyl-4-hexyl-3-hydroxy-20-nitrobiphenyl-2-carboxy-
late (6h). Starting with 5d (1.516 g, 4.4 mmol), TiCl4 (0.834 g,
4.4 mmol), CH2Cl2 (8 mL) and 4b (1.170 g, 4.0 mmol), 6h was iso-
lated (0.631 g, 41%) as a yellowish oil. 1H NMR (CDCl3, 250 MHz):
43%) as a yellowish oil. 1H NMR (CDCl3, 250 MHz):
d¼1.05 (t,
3J¼7.5 Hz, 3H, CH2CH3), 2.45 (q, 3J¼7.5 Hz, 2H, CH2CH3), 3.27 (s, 3H,
OCH3), 6.31 (d, 4J¼2.0 Hz, 1H, CHAr), 6.70 (d, 4J¼1.7 Hz, 1H, CHAr),
7.07 (dd, 3J¼7.7 Hz, 4J¼1.3 Hz, 1H, CHAr), 7.31 (ddd, 3J¼7.0 Hz,
3J¼7.0 Hz, 4J¼1.5 Hz, 1H, CHAr), 7.43 (ddd, 3J¼7.5 Hz, 3J¼7.5 Hz,
4J¼1.5 Hz, 1H, CHAr), 7.87 (dd, 3J¼8.4 Hz, 4J¼1.3 Hz, 1H, CHAr), 11.05
d
¼0.78 (t, 3J¼7.3 Hz, 3H, (CH2)5CH3), 1.06 (t, 3J¼7.6 Hz, 3H, CH2CH3),
1.08–1.14 (m, 8H, 4ꢂCH2), 2.46 (q, 3J¼7.2 Hz, 2H, CH2CH3), 2.48–2.52
(m, 2H, CH2), 3.32 (s, 3H, OCH3), 6.35 (s, 1H, CHAr), 6.99 (dd,
3J¼7.6 Hz, 4J¼1.3 Hz, 1H, CHAr), 7.35 (ddd, 3J¼7.0 Hz, 3J¼7.0 Hz,
4J¼1.5 Hz, 1H, CHAr), 7.45 (ddd, 3J¼7.5 Hz, 3J¼7.5 Hz, 4J¼1.5 Hz, 1H,
(s,1H, OH). 13C NMR (CDCl3, 75 MHz):
(OCH3), 108.8 (CCOOCH3), 117.2, 121.5, 123.8, 127.8, 131.3, 132.5
d
¼14.6 (CH3), 28.9 (CH2), 52.4
CHAr), 7.88 (dd, 3J¼8.5 Hz, 4J¼1.3 Hz, 1H, CHAr), 11.43 (s, 1H, OH). 13
C
(CHAr), 138.5, 140.4, 148.1, 151.8, 162.8 (CAr), 170.4 (CO). IR (neat,
NMR (CDCl3, 62 MHz):
d¼14.9, 17.3 (CH3), 22.6, 25.9, 26.1, 29.4, 29.8,
cmꢁ1):
31.7 (CH2), 51.8 (OCH3), 108.1 (CCOOCH3), 121.2, 123.5, 127.5, 131.2,
~
n
¼3022 (w), 2949 (w), 2872 (w),1659 (s),1607 (m),1571 (m),
1522 (s), 1436 (m), 1417 (w), 1386 (w), 1344 (s), 1272 (m), 1211 (s),
1160 (m), 1145 (m), 1102 (m), 1039 (w), 947 (w), 870 (w), 804 (m),
743 (s), 688 (s), 635 (m), 544 (w). GC–MS (EI, 70 eV): m/z (%)¼301
([M]þ, 45), 270 (15), 269 (86), 256 (17), 255 (100), 242 (14), 241 (16),
240 (18), 213 (18), 198 (10), 197 (17), 196 (14), 195 (21), 181 (14), 180
(12),170 (16),168 (16),167 (16),166 (10),165 (26),153 (12),152 (36),
151 (14), 139 (15), 128 (12), 127 (11), 115 (24), 77 (11), 76 (10). HRMS
(EI): Calcd for C16H15NO5: 301.09447; found: 301.094496.
132.1 (CHAr), 129.3, 137.0, 138.7, 142.9, 148.9, 160.7 (CAr), 170.0 (CO).
IR (neat, cmꢁ1):
n
¼3066 (w), 2954 (w), 2856 (w), 1661 (s), 1606 (w),
~
1564 (w), 1526 (s), 1439 (m), 1399 (m), 1349 (m), 1273 (m), 1213 (m),
1175 (m), 1118 (w), 1035 (w), 908 (m), 854 (w), 786 (w), 732 (s), 708
(w), 633 (w). GC–MS (EI, 70 eV): m/z (%)¼386 ([M]þþ1, 25), 385
([M]þ, 100), 339 (21), 338 (64), 336 (23), 292 (29), 290 (10), 282 (47),
268 (20), 253 (10), 252 (10), 250 (15), 249 (36), 248 (27), 240 (11),
239 (50), 238 (21), 237 (30), 235 (18), 234 (12), 224 (14), 223 (19),
222 (53), 221 (13), 210 (20), 208 (39), 207 (38),195 (13),194 (42),193
(22), 181 (10), 180 (12), 179 (19), 178 (37), 167 (14), 166 (13), 153 (11),
152 (20), 115 (12), 43 (20), 41 (15), 29 (12). HRMS (EI): Calcd for
C22H27NO5: 385.18837; found: 385.187845.
4.4.6. Methyl5-ethyl-3-hydroxy-4-methyl-20-nitrobiphenyl-2-carboxy-
late (6f). Starting with 5b (1.207 g, 4.4 mmol), TiCl4 (0.834 g,
4.4 mmol), CH2Cl2 (8 mL) and 4b (1.170 g, 4.0 mmol), 6f was isolated
(0.530 g, 42%) as a yellowish oil. 1H NMR (CDCl3, 250 MHz):
d
¼1.05
(t, 3J¼7.4 Hz, 3H, CH2CH3), 2.12 (s, 3H, CH3), 2.52 (q, 3J¼7.5 Hz, 2H,
CH2CH3), 3.32 (s, 3H, OCH3), 6.35 (s, 1H, CHAr), 7.12 (dd, 3J¼7.3 Hz,
4J¼1.4 Hz, 1H, CHAr), 7.34 (ddd, 3J¼7.6 Hz, 3J¼7.6 Hz, 4J¼1.8 Hz, 1H,
4.4.9. Methyl 5-ethyl-4-heptyl-3-hydroxy-20-nitrobiphenyl-2-carboxy-
late (6i). Starting with 5e (2.367 g, 6.6 mmol), TiCl4 (1.251 g,
6.6 mmol), CH2Cl2 (12 mL) and 4b (1.760 g, 6.0 mmol), 6i was isolated

9306
A. Riahi et al. / Tetrahedron 65 (2009) 9300–9315
(0.934 g, 39%) as a yellowish oil. 1H NMR (CDCl3, 250 MHz):
d
¼0.79–
(0.835 g, 4.4 mmol), CH2Cl2 (8 mL) and 4c (1.229 g, 4.0 mmol), 6l
0.80 (m, 3H, (CH2)6CH3), 1.12 (t, 3J¼7.6 Hz, 3H, CH2CH3),1.21–1.26 (m,
10H, 5ꢂCH2), 2.57 (q, 3J¼7.3 Hz, 2H, CH2CH3), 2.61–2.66 (m, 2H, CH2),
3.37 (s, 3H, OCH3), 6.40 (s,1H, CHAr), 7.17 (dd, 3J¼7.4 Hz, 4J¼1.4 Hz,1H,
CHAr), 7.38 (ddd, 3J¼7.1 Hz, 3J¼7.2 Hz, 4J¼1.5 Hz, 1H, CHAr), 7.51 (ddd,
3J¼7.6 Hz, 3J¼7.5 Hz, 4J¼1.5 Hz, 1H, CHAr), 7.92 (dd, 3J¼7.9 Hz,
4J¼1.3 Hz, 1H, CHAr), 11.48 (s, 1H, OH). 13C NMR (CDCl3, 62 MHz):
was isolated (0.500 g, 38%) as a yellowish oil. 1H NMR (CDCl3,
250 MHz):
d
¼0.82 (t, 3J¼7.6 Hz, 3H, CH3), 1.41–1.50 (m, 2H, CH2),
2.12(s, 3H, CH3), 2.47 (t, 3J¼7.5 Hz, 2H, CH2), 3.32 (s, 3H, OCH3), 6.34
(s, 1H, CHAr), 7.11 (dd, 3J¼8.7 Hz, 4J¼1.5 Hz, 1H, CHAr), 7.34 (ddd,
3J¼8.0 Hz, 3J¼7.9 Hz, 4J¼1.4 Hz, 1H, CHAr), 7.45 (ddd, 3J¼7.5 Hz,
3J¼7.5 Hz, 4J¼1.5 Hz, 1H, CHAr), 7.88 (dd, 3J¼7.5 Hz, 4J¼1.6 Hz, 1H,
CHAr), 11.49 (s, 1H, OH). 13C NMR (CDCl3, 62 MHz): dC¼10.3, 12.9
(CH3), 22.1, 35.0 (CH2), 50.8 (OCH3), 107.0 (CAr), 121.0, 122.6 (CHAr),
127.7 (CHAr), 126.5, 130.3, 131.2 (CHAr), 135.8, 137.6, 146.8, 147.0,
159.8 (CHAr), 170.1 (C]O). GC–MS (EI, 70 eV): m/z (%)¼329 ([M]þ,
55), 297 (100), 283 (20), 238 (18), 224 (30), 208 (14), 194 (12), 165
(25), 139 (7), 115 (9), 77 (5). HRMS (EI): Calcd for C18H19NO5:
329.12577; found: 329.12597.
d
¼13.1, 16.3 (CH3), 21.7, 24.9, 25.1, 28.2, 28.5, 29.1, 30.9 (CH2), 50.8
(OCH3),107.1 (CCOOCH3), 120.2, 122.5, 126.5, 130.3, 131.1 (CHAr),124.9,
136.1, 137.6, 141.9, 147.8, 159.7 (CAr), 170.0 (CO). IR (neat, cmꢁ1):
~
n
¼3066 (w), 2953 (w), 2853 (w), 1660 (m), 1606 (w), 1564 (w), 1525
(s), 1438 (m), 1399 (m), 1347 (m), 1281 (m), 1212 (m), 1174 (m), 1118
(w), 1055 (w), 907 (m), 854 (w), 782 (w), 730 (s), 708 (m), 633 (w).
GC–MS (EI, 70 eV): m/z (%)¼400 ([M]þþ1, 28), 399 ([M]þ, 100), 353
(20), 350 (22), 322 (10), 306 (27), 282 (48), 268 (20), 264 (10), 263
(10), 253 (15), 252 (12), 250 (15), 249 (33), 248 (27), 240 (11), 239 (51),
238 (25), 237 (32), 236 (17), 235 (18), 234 (12), 224 (20), 223 (20), 222
(53), 221 (13), 210 (17), 209 (17), 208 (45), 207 (36),195 (13),194 (38),
193 (20), 181 (10), 180 (12), 179 (17), 178 (33), 167 (14), 166 (50), 165
(15), 153 (9), 152 (17), 115 (11), 43 (26), 41 (17), 29 (13). HRMS (EI):
Calcd for C23H29NO5: 399.20402; found: 399.202985.
4.4.13. Ethyl 4-ethyl-3-hydroxy-20-nitro-5-propylbiphenyl-2-carboxy-
late (6m). Starting with 5c (0.998 g, 3.3 mmol), TiCl4 (0.625 g,
3.3 mmol), CH2Cl2 (7 mL) and 4c (0.876 g, 3.0 mmol), 6m was iso-
lated (0.400 g, 37%) as a yellowish oil. 1H NMR (CDCl3, 250 MHz):
d
¼0.59 (t, 3J¼7.3 Hz, 3H, CH3), 0.83 (t, 3J¼6.5 Hz, 3H, CH3), 1.07 (t,
3J¼7.4 Hz, 3H, CH3), 1.39–1.48 (m, 2H, CH2), 2.43–2.50 (m, 2H, CH2),
2.57–2.66 (m, 2H, CH2), 3.82 (q, 3J¼6.5 Hz, 2H, OCH2), 6.32 (s, 1H,
CHAr), 7.12 (dd, 3J¼7.5 Hz, 4J¼1.5 Hz, 1H, CHAr), 7.34 (ddd, 3J¼8.0 Hz,
3J¼7.5 Hz, 4J¼1.5 Hz, 1H, CHAr), 7.44 (ddd, 3J¼7.5 Hz, 3J¼7.4 Hz,
4J¼1.5 Hz,1H, CHAr), 7.88 (dd, 3J¼7.6 Hz, 4J¼1.3 Hz,1H, CHAr),11.58 (s,
1H, OH).13C NMR (CDCl3, 62 MHz): dC¼8.9,14.4,15.2 (CH3), 20.3, 25.1,
36.3 (CH2), 62.0 (OCH2), 109.4 (CAr), 123.1, 124.7, 128.6 (CHAr), 131.7
(CAr), 132.4, 133.2 (CHAr), 137.9, 140.1, 148.1, 149.1, 162.0 (CAr), 171.8
(C]O). GC–MS (EI, 70 eV): m/z (%)¼357 ([M]þ, 100), 311 (54), 283
(21), 266 (38), 250 (43), 235 (20), 220 (58), 194 (20), 180 (39), 165
(39), 152 (27), 115 (15), 77 (11). HRMS (EI): Calcd for C20H23NO5:
357.15707; found: 329.15710.
4.4.10. Methyl 5-ethyl-3-hydroxy-20-nitro-4-octylbiphenyl-2-carb-
oxylate (6j). Starting with 5f (1.639 g, 4.4 mmol), TiCl4 (0.834 g,
4.4 mmol), CH2Cl2 (8 mL) and 4b (1.173 g, 4.0 mmol), 6j was isolated
(0.627 g, 38%) as a yellowish oil. 1H NMR (CDCl3, 250 MHz):
d
¼0.71
(t, 3J¼7.3 Hz, 3H, (CH2)7CH3), 1.02 (t, 3J¼7.5 Hz, 3H, CH2CH3), 1.04–
1.12 (m, 12H, 6ꢂCH2), 2.47 (q, 3J¼7.3 Hz, 2H, CH2CH3), 2.52–2.55 (m,
2H, CH2), 3.27 (s, 3H, OCH3), 6.30 (s, 1H, CHAr), 7.08 (dd, 3J¼7.3 Hz,
4J¼1.1 Hz, 1H, CHAr), 7.28 (ddd, 3J¼7.7 Hz, 3J¼7.7 Hz, 4J¼1.3 Hz, 1H,
CHAr), 7.40 (ddd, 3J¼7.3 Hz, 3J¼7.3 Hz, 4J¼1.3 Hz, 1H, CHAr), 7.84 (dd,
3J¼8.5 Hz, 4J¼1.5 Hz, 1H, CHAr), 11.38 (s, 1H, OH). 13C NMR (CDCl3,
62 MHz):
d
¼15.2, 16.1 (CH3), 23.8, 27.1, 27.3, 30.3, 30.4, 30.5, 30.7,
33.1 (CH2), 50.0 (OCH3), 109.4 (CCOOCH3), 122.3, 124.7, 128.7, 132.4,
4.4.14. Methyl 4-hexyl-3-hydroxy-20-nitro-5-propylbiphenyl-2-carb-
oxylate (6n). Starting with 5d (1.1366 g, 3.3 mmol), TiCl4 (0.625 g,
3.3 mmol), CH2Cl2 (6 mL) and 4c (0.876 g, 3.0 mmol), 6n was iso-
lated (0.315 g, 26%) as a yellow oil. 1H NMR (CDCl3, 250 MHz):
133.3 (CHAr), 130.4, 138.2, 139.9, 149.3, 150.0, 162.2 (CAr), 172.2 (CO).
IR (neat, cmꢁ1):
~
n
¼2953 (w), 2853 (w),1753 (w),1661 (m),1606 (m),
1563 (w), 1526 (s), 1437 (m),1398 (m),1348 (m),1275 (m),1213 (m),
1174 (m), 1120 (w), 1053 (w), 904 (m), 841 (w), 753 (m), 706 (m),
630 (w). GC–MS (EI, 70 eV): m/z (%)¼414 ([M]þþ1, 28), 413 ([M]þ,
100), 368 (11), 367 (42), 354 (13), 353 (22), 352 (91), 336 (19), 320
(14), 306 (20), 283 (14), 282 (82), 266 (20), 253 (21), 252 (16), 250
(15), 249 (15), 248 (20), 240 (12), 239 (46), 238 (25), 237 (27), 236
(24), 235 (23), 234 (12), 224 (34), 223 (16), 222 (49), 221 (20), 210
(14), 209 (14), 208 (35), 207 (23), 206 (11), 205 (10), 196 (12), 194
(30),193 (29),192 (14),181 (12),180 (12),179 (14),178 (26),167 (14),
166 (12), 165 (54), 153 (9), 152 (20), 55 (12), 43 (26), 41 (25), 29 (16).
HRMS (EI): Calcd for C24H31NO5: 413.21967; found: 413.220441.
d¼0.70–0.81 (m, 6H, 2ꢂCH3), 1.34–1.43 (m, 4H, 2ꢂCH2), 2.38–2.44
(m, 2H, CH2), 2.47–2.55 (m, 2H, CH2), 3.26 (s, 3H, OCH3), 6.28 (s, 1H,
CHAr), 7.06 (dd, 3J¼7.5 Hz, 4J¼1.3 Hz, 1H, CHAr), 7.28 (ddd, 3J¼7.5 Hz,
3J¼7.5 Hz, 4J¼1.5 Hz, 1H, CHAr), 7.40 (ddd, 3J¼7.5 Hz, 3J¼7.5 Hz,
4J¼1.5 Hz, 1H, CHAr), 7.82 (dd, 3J¼7.6 Hz, 4J¼1.3 Hz, 1H, CHAr), 11.39
(s,1H, OH). 13C NMR (CDCl3, 62 MHz): dC¼15.2,15.3 (CH3), 22.8, 25.1,
27.2, 30.7, 31.0, 32.9, 36.4 (CH2), 53.0 (OCH3),109.4 (CAr),123.4,124.7,
128.8 (CHAr), 130.8 (CAr), 132.4, 133.4 (CHAr), 138.0, 139.9, 148.6,
149.3, 162.0 (CAr), 171.2 (C]O). GC–MS (EI, 70 eV): m/z (%)¼399
([M]þ, 100), 353 (18), 350 (11), 340 (13), 325 (15), 324 (89), 322 (14),
306 (17), 296 (41), 278 (14), 253 (16), 238 (13), 236 (17), 235 (13),
224 (14), 222 (13), 220 (10), 208 (11), 207 (11),193 (10),177 (18),165
(14),164 (10),161 (12),149 (10),111 (11),109 (12), 97 (16), 85 (14), 83
(17), 81 (15), 71 (22), 57 (37), 55 (26), 43 (27), 41 (21). HRMS (EI):
Calcd for C23H29NO5: 399.20402; found: 399.203444.
4.4.11. Methyl
3-hydroxy-20-nitro-5-propylbiphenyl-2-carboxylate
(6k). Starting with 5a (1.145 g, 4.4 mmol), TiCl4 (0.835 g, 4.4 mmol),
CH2Cl2 (8 mL) and 4c (1.229 g, 4.0 mmol), 6k was isolated (0.607 g,
48%) as a yellow gummy solid. 1H NMR (CDCl3, 250 MHz):
d
¼0.80 (t,
3J¼7.5 Hz, 3H, CH3), 1.47–1.56 (m, 2H, CH2), 2.44 (t, 3J¼7.0 Hz, 2H,
CH2), 3.27 (s, 3H, OCH3), 6.36 (d, 4J¼1.8 Hz, 1H, CHAr), 6.74 (d,
4J¼1.8 Hz, 1H, CHAr), 7.12 (dd, 3J¼7.5 Hz, 4J¼1.8 Hz, 1H, CHAr), 7.36
(ddd, 3J¼7.3 Hz, 3J¼7.0 Hz, 4J¼1.4 Hz, 1H, CHAr), 7.47 (ddd, 3J¼7.6 Hz,
3J¼7.3 Hz, 4J¼1.5 Hz, 1H, CHAr), 7.91 (dd, 3J¼7.2 Hz, 4J¼1.2 Hz, 1H,
CHAr),11.10 (s,1H, OH).13C NMR (CDCl3, 62 MHz): dC¼13.8 (CH3), 23.4,
37.7 (CH2), 51.8 (OCH3), 108.6 (CAr), 117.3, 122.0, 123.7, 127.8, 131.1,
132.5 (CHAr), 138.4, 140.3, 147.8, 150.2, 162.4 (CAr), 170.3 (C]O). GC–
MS (EI, 70 eV): m/z (%)¼315 ([M]þ, 47), 269 (100), 255 (17), 240 (11),
227 (14), 197 (10), 181 (18), 165 (16), 152 (31), 115 (19), 77 (8). HRMS
(EI): Calcd for C17H17NO5: 315.11062; found: 315.11032.
4.4.15. Methyl
5-butyl-3-hydroxy-20-nitrobiphenyl-2-carboxylate
(6o). Starting with 5a (1.289 g, 4.9 mmol), TiCl4 (0.938 g, 4.9 mmol),
CH2Cl2 (9 mL) and 4d (1.446 g, 4.5 mmol), 6o was isolated (0.621 g,
42%) as a yellowish oil. 1H NMR (CDCl3, 250 MHz):
d
¼0.78 (t,
3J¼7.3 Hz, 3H, (CH2)3CH3), 1.17–1.26 (m, 2H, CH2), 1.41–1.53 (m, 2H,
CH2), 2.46 (t, 3J¼7.9 Hz, 2H, CH2(CH2)2CH3), 3.32 (s, 3H, OCH3), 6.35
(d, 4J¼1.7 Hz, 1H, CHAr), 6.74 (d, 4J¼1.7 Hz, 1H, CHAr), 7.12 (dd,
3J¼7.5 Hz, 4J¼1.6 Hz, 1H, CHAr), 7.36 (ddd, 3J¼7.7 Hz, 3J¼8.1 Hz,
4J¼1.6 Hz, 1H, CHAr), 7.47 (ddd, 3J¼7.5 Hz, 3J¼7.7 Hz, 4J¼1.5 Hz, 1H,
CHAr), 7.92 (dd, 3J¼7.7 Hz, 4J¼1.2 Hz, 1H, CHAr), 11.10 (s, 1H, OH). 13
C
NMR (CDCl3, 75 MHz):
(OCH3), 107.6 (CCOOCH3), 116.4, 120.9, 122.7, 126.9, 130.1, 131.3
d
¼12.9 (CH3), 21.3, 31.6, 34.6 (CH2), 50.9
4.4.12. Methyl
carboxylate (6l). Starting with 5b (1.207 g, 4.4 mmol), TiCl4
3-hydroxy-4-methyl-20-nitro-5-propylbiphenyl-2-
(CHAr), 137.3, 139.2, 146.9, 149.5, 161.5 (CAr), 169.4 (CO). IR (neat,

A. Riahi et al. / Tetrahedron 65 (2009) 9300–9315
9307
cmꢁ1):
n
¼3066 (w), 2954 (w), 2859 (w),1662 (s),1608 (m),1570 (m),
(ddd, 3J¼7.5 Hz, 3J¼7.2 Hz, 4J¼1.5 Hz, 1H, CHAr), 8.0 (dd, 3J¼8.1 Hz,
4J¼1.5 Hz, 1H, CHAr), 11.19 (s, 1H, OH). 13C NMR (CDCl3, 62 MHz):
~
1522 (s), 1438 (m), 1417 (m), 1346 (s), 1266 (s), 1216 (s), 1161 (m),
1146 (m),1103 (m),1008 (w), 950 (w), 856 (w), 808 (m), 753 (m), 702
(s), 632 (w), 545 (w). GC–MS (EI, 70 eV): m/z (%)¼329 ([M]þ, 43), 297
(32), 284 (20), 283 (100), 270 (14), 256 (10), 255 (56), 226 (12), 182
(12),181 (15),180 (15),166 (10),165 (13),154 (26),153 (12),152 (27),
151 (10), 139 (10), 115 (15), 97 (12). HRMS (EI): Calcd for C18H19NO5:
329.12577; found: 329.125715.
d¼13.9, 14.1, 16.4 (CH3), 22.4, 25.8, 28.5, 29.9, 31.4, 31.8 (CH2), 51.8
(OCH3), 108.5 (CCOOCH3), 123.7, 127.5, 131.1, 132.6 (CHAr), 125.1,
129.3, 136.1, 138.5, 148.3, 148.4, 158.6 (CAr), 171.6 (CO). IR (neat,
cmꢁ1):
~
n
¼2954 (w), 2926 (m), 2856 (w), 1753 (m), 1659 (s), 1594
(w), 1525 (s), 1438 (m), 1411 (m), 1348 (s), 1263 (m), 1211 (s), 1175
(m), 1119 (w), 1016 (w), 919 (w), 853 (w), 788 (w), 752 (m), 707 (w),
627 (w). GC–MS (EI, 70 eV): m/z (%)¼400 ([M]þþ1, 15), 399 ([M]þ,
59), 339 (23), 338 (100), 296 (27), 292 (23), 263 (11), 253 (10), 252
(10), 250 (10), 249 (21), 238 (17), 236 (13), 234 (10), 222 (14), 221
(10), 208 (14), 207 (21), 179 (13), 178 (21), 165 (14), 152 (9), 43 (13),
41 (10). HRMS (EI): Calcd for C23H29NO5: 399.20402; found:
399.203491.
4.4.16. Methyl 5-butyl-3-hydroxy-4-methyl-20-nitrobiphenyl-2-carb-
oxylate (6p). Starting with 5b (1.509 g, 5.5 mmol), TiCl4 (1.043 g,
5.5 mmol), CH2Cl2 (10 mL) and 4d (1.607 g, 5.0 mmol), 6p was
isolated (0.670 g, 39%) as a yellowish oil. 1H NMR (CDCl3, 250 MHz):
d
¼0.79 (t, 3J¼7.1 Hz, 3H, (CH2)3CH3), 1.19–1.28 (m, 2H, CH2), 1.30–
1.44 (m, 2H, CH2), 2.12 (s, 3H, CH3), 2.49 (t, 3J¼7.1 Hz, 2H,
CH2(CH2)2CH3), 3.32 (s, 3H, OCH3), 6.34 (s, 1H, CHAr), 7.11 (dd,
3J¼7.4 Hz, 4J¼1.3 Hz, 1H, CHAr), 7.34 (ddd, 3J¼8.0 Hz, 3J¼8.1 Hz,
4J¼1.6 Hz, 1H, CHAr), 7.45 (ddd, 3J¼8.0 Hz, 3J¼7.7 Hz, 4J¼1.6 Hz, 1H,
4.4.19. Methyl 6-chloro-3-hydroxy-20-nitro-5-propylbiphenyl-2-carb-
oxylate (6s). Starting with 5a (1.260 g, 4.8 mmol), TiCl4 (0.920 g,
4.8 mmol), CH2Cl2 (9 mL) and 4f (1.50 g, 4.4 mmol), 6s was isolated
CHAr), 7.88 (dd, 3J¼8.2 Hz, 4J¼1.6 Hz, 1H, CHAr), 11.48 (s, 1H, OH). 13
C
(0.841 g, 55%) as a yellowish oil. 1H NMR (CDCl3, 250 MHz):
d¼0.87
NMR (CDCl3, 75 MHz):
d
¼13.3, 16.0 (CH3), 24.7, 34.1, 35.8 (CH2),
(t, 3J¼7.5 Hz, 3H, (CH2)2CH3), 1.51–1.59 (m, 2H, CH2), 2.58 (t,
3J¼7.5 Hz, 2H, CH2CH2CH3), 3.28 (s, 3H, OCH3), 6.84 (s, 1H, CHAr),
7.03 (dd, 3J¼7.5 Hz, 4J¼1.8 Hz, 1H, CHAr), 7.42 (ddd, 3J¼8.1 Hz,
3J¼8.1 Hz, 4J¼1.8 Hz, 1H, CHAr), 7.55 (ddd, 3J¼8.1 Hz, 3J¼8.1 Hz,
4J¼1.7 Hz, 1H, CHAr), 8.08 (dd, 3J¼7.8 Hz, 4J¼1.8 Hz, 1H, CHAr), 10.94
53.9 (OCH3), 110.0 (CCOOCH3), 124.0, 125.6, 129.7, 133.4, 134.3
(CHAr), 126.7, 136.5, 138.9, 140.7, 150.2, 163.0 (CAr), 173.0 (CO). IR
(neat, cmꢁ1):
n
¼2953 (w), 2870 (w), 1659 (s), 1606 (m), 1566 (m),
~
1522 (s), 1437 (m), 1397 (m), 1345 (s), 1267 (s), 1196 (m), 1173 (m),
1144 (m), 1112 (m), 1010 (m), 962 (w), 852 (m), 809 (m), 752 (m),
705 (m), 633 (w), 546 (w). GC–MS (EI, 70 eV): m/z (%)¼344
([M]þþ1, 11), 343 ([M]þ, 53), 312 (20), 311 (100), 297 (22), 225 (19),
224 (18), 208 (24), 207 (10), 195 (11), 194 (14), 181 (10), 180 (15), 167
(11), 166 (10), 165 (26), 152 (18), 115 (10). HRMS (EI): Calcd for
C19H21NO5: 343.14142; found: 343.141424.
(s,1H, OH).13C NMR (CDCl3, 75 MHz):
52.3 (OCH3), 69.68 (CHAr),110.3 (CCOOCH3),124.4,130.0,131.7,134.9
d
¼13.8 (CH3), 22.2, 36.4 (CH2),
(CHAr), 128.3, 136.3, 138.9, 145.3, 148.2, 160.7 (CAr), 169.8 (CO). IR
(neat, cmꢁ1):
~
n
¼3102 (w), 3017 (w), 2959 (w), 2862 (w), 1723 (m).
1668 (w), 1601 (w), 1569 (w), 1524 (s), 1440 (m), 1340 (s), 1297 (m),
1266 (m), 1196 (m), 1164 (w), 1144 (m), 1113 (w), 1040 (w), 997 (m),
857 (m), 787 (s), 762 (m), 717 (m), 698 (s), 650 (m), 634 (s), 555 (w).
GC–MS (EI 70 eV): m/z (%)¼351 ([Mþ], 37Cl, 25), 349 ([Mþ], 35Cl, 71),
317 (20), 314 (44), 313 (11), 305 (12), 303 (35), 290 (10), 283 (18),
282 (100), 274 (18), 272 (24), 257 (16), 255 (13), 254 (70), 246 (11),
244 (20), 231 (14), 230 (13), 227 (17), 226 (33), 225 (38), 218 (15),
216 (13), 215 (14), 214 (15), 209 (18), 208 (11), 198 (21), 195 (13), 193
(24),186 (11),182 (13),181 (17),180 (22),178 (23),177 (34),170 (10),
168 (21), 167 (19), 166 (10), 165 (26), 163 (13), 158 (10), 155 (16), 153
(24),152 (49),151 (33),149 (17),139 (40),131 (13),128 (15),126 (16),
124 (21), 115 (12), 114 (10), 77 (11), 76 (12), 75 (11), 67 (14), 29 (10).
HRMS (EI): Calcd for C17H16NO5Cl: 349.07115; found: 349.070500.
4.4.17. Methyl 5-butyl-4-hexyl-3-hydroxy-20-nitrobiphenyl-2-carboxy-
late (6q). Starting with 5d (2.274 g, 6.6 mmol), TiCl4 (1.251 g,
6.6 mmol), CH2Cl2 (12 mL) and 4d (1.928 g, 6.0 mmol), 6q was
isolated (0.941 g, 38%) as a yellowish oil. 1H NMR (CDCl3, 250 MHz):
d
¼0.74 (m, 6H, 2ꢂCH3), 1.08–1.25 (m, 12H, 6ꢂCH2), 2.42 (t,
3J¼7.4 Hz, 2H, CH2(CH2)2CH3), 2.48–2.55 (m, 2H, CH2), 3.26 (s, 3H,
OCH3), 6.28 (s, 1H, CHAr), 7.07 (dd, 3J¼8.1 Hz, 4J¼1.6 Hz, 1H, CHAr),
7.28 (ddd, 3J¼7.4 Hz, 3J¼7.4 Hz, 4J¼1.6 Hz, 1H, CHAr), 7.42 (ddd,
3J¼7.1 Hz, 3J¼7.7 Hz, 4J¼1.6 Hz, 1H, CHAr), 7.83 (dd, 3J¼8.1 Hz,
4J¼1.6 Hz, 1H, CHAr), 11.38 (s, 1H, OH). 13C NMR (CDCl3, 75 MHz):
d
¼15.1, 15.2 (CH3), 23.8, 23.9, 27.2, 30.6, 31.0, 32.9, 34.2, 34.3 (CH2),
52.9 (OCH3), 109.3 (CCOOCH3), 123.2, 124.7, 128.7, 132.5, 133.4
4.4.20. Methyl 3-hydroxy-4,5-dimethyl-30-nitrobiphenyl-2-carboxy-
late (6t). Starting with 5b (0.598 g, 2.2 mmol), TiCl4 (0.413 g,
2.2 mmol), CH2Cl2 (4 mL) and 4g (0.548 g, 2.0 mmol), 6t was iso-
lated (0.305 g, 50%) as a yellowish oil. 1H NMR (CDCl3, 250 MHz):
(CHAr), 130.7, 138.0, 139.9, 148.9, 149.3, 162.1 (CAr), 172.2 (CO). IR
(neat, cmꢁ1):
n
¼2954 (m), 2856 (m), 1933 (w), 1702 (w), 1661 (m),
~
1606 (m), 1562 (w), 1525 (s), 1437 (m), 1397 (m), 1347 (s), 1271 (m),
1228 (m), 1174 (m), 1145 (m), 1121 (m), 1009 (w), 954 (w), 842 (m),
813 (m), 754 (m), 706 (m), 632 (w), 562 (w). GC–MS (EI 70 eV): m/z
(%)¼414 ([M]þþ1, 27), 413 ([M]þ, 98), 368 (11), 367 (38), 364 (11),
336 (19), 325 (22), 324 (100), 320 (20), 310 (26), 300 (10), 280 (11),
278 (25), 276 (16), 264 (14), 252 (13), 250 (22), 249 (17), 248 (11),
239 (13), 238 (13), 236 (20), 235 (26), 234 (19), 233 (10), 226 (11),
225 (54), 224 (15), 223 (15), 222 (16), 221 (15), 220 (20), 210 (13),
209 (12), 208 (26), 207 (15), 206 (10), 196 (12), 195 (14), 194 (33),
193 (14), 181 (13), 180 (22), 179 (12), 178 (20), 167 (14), 166 (14), 165
(36), 152 (21), 43 (23), 41 (20), 29 (13). HRMS (EI): Calcd for
C24H31NO5: 413.21967; found: 413.219007.
d¼2.09 (s, 3H, CH3), 2.21 (s, 3H, CH3), 3.36 (s, 3H, OCH3), 6.46 (s, 1H,
CHAr), 7.30–7.40 (m, 2H, CHAr), 7.97 (m, 1H, CHAr), 8.03–8.07 (m, 1H,
CHAr), 11.19 (s, 1H, OH). 13C NMR (CDCl3, 75 MHz): dC¼12.0, 21.3
(CH3), 52.1 (OCH3), 108.7 (CAr), 121.9, 123.5, 124.3 (CHAr), 125.7 (CAr),
128.6, 134.9 (CHAr), 139.0, 144.0, 145.4, 148.1, 160.7, (CAr), 171.6
(C]O). GC–MS (EI 70 eV): m/z (%)¼301 ([M]þ, 46), 269 (100), 252
(66), 222 (40),195 (17),165 (33), 152 (28),139 (7), 82 (5). HRMS (EI):
Calcd for C16H15NO5: 301.09444; found: 301.09431.
4.4.21. Ethyl 4-ethyl-3-hydroxy-5-methyl-30-nitrobiphenyl-2-carb-
oxylate (6u). Starting with 5c (0.659 g, 2.2 mmol), TiCl4 (0.41 g,
2.2 mmol), CH2Cl2 (4 mL) and 4g (0.548 g, 2.0 mmol), 6u was iso-
lated (0.250 g, 37%) as a yellow gummy solid, mp¼90–92 ꢀC. 1H
4.4.18. Methyl
5-ethyl-4-hexyl-3-hydroxy-6-methyl-20-nitrobiphenyl-
2-carboxylate (6r). Starting with 5d (2.274 g, 6.6 mmol), TiCl4
(1.251 g, 6.6 mmol), CH2Cl2 (12 mL) and 4e (1.844 g, 6.0 mmol), 6r
was isolated (0.577 g, 38%) as a yellowish oil. 1H NMR (CDCl3,
NMR (CDCl3, 300 MHz):
d
¼0.63 (t, 3J¼7.7 Hz, 3H, CH3), 1.04 (t,
3J¼7.7 Hz, 3H, CH3), 2.23 (s, 3H, CH3), 2.62 (q, 3J¼7.0 Hz, 2H, CH2),
3.87 (q, 3J¼6.0 Hz, 2H, OCH2), 6.46 (s, 1H, CHAr), 7.37–7.45 (m, 2H,
CHAr), 7.99 (m, 1H, CHAr), 8.03–8.07 (m, 1H, CHAr), 11.32 (s, 1H, OH).
13C NMR (CDCl3, 75 MHz): dC¼11.9, 12.0, 18.4 (CH3), 18.6 (CH2), 60.0
(OCH2), 107.6 (CAr), 120.3, 122.2, 123.1, 127.2, 130.3 (CHAr), 133.5,
137.8, 141.6, 144.1, 146.6, 159.3 (CAr), 169.7 (C]O). GC–MS (EI,
250 MHz):
d
¼0.78–0.81 (m, 3H, (CH2)5CH3), 1.07 (t, 3J¼7.6 Hz, 3H,
CH2CH3), 1.29–1.33 (m, 8H, 4ꢂCH2), 2.49 (s, 3H, CH3), 2.56–2.68 (m,
4H, 2ꢂCH2), 3.28 (s, 3H, OCH3), 7.04 (dd, 3J¼7.8 Hz, 4J¼1.5 Hz, 1H,
CHAr), 7.40 (ddd, 3J¼7.8 Hz, 3J¼7.8 Hz, 4J¼1.5 Hz, 1H, CHAr), 7.51

9308
A. Riahi et al. / Tetrahedron 65 (2009) 9300–9315
70 eV): m/z (%)¼329 ([M]þ, 58), 283 (92), 266 (100), 236 (23), 209
(30), 194 (8), 178 (11), 165 (41), 152 (16), 139 (7), 115 (6). HRMS (EI):
Calcd for C18H19NO5: 329.12577; found: 329.12659.
100), 206 (10), 196 (16), 99 (14), 73 (16), 57 (27), 43 (52). HRMS (EI):
Calcd for C14H11NO2: 225.07853; found: 225.07843.
4.5.2. 7-Hydroxy-8,9-dimethylphenanthridin-6(5H)-one
(7b). Starting with 6b (0.504 g, 1.7 mmol), 7b was isolated (0.200 g,
52%) by column chromatography (silica gel, heptanes/
EtOAc¼30:1/20:1) as a colourless solid, mp¼260–261 ꢀC. 1H NMR
4.4.22. Methyl 3-hydroxy-5-methyl-40-nitrobiphenyl-2-carboxylate
(6v). Starting with 5a (0.568 g, 2.2 mmol), TiCl4 (0.413 g,
2.2 mmol), CH2Cl2 (4 mL) and 4h (0.558 g, 4.0 mmol), 6v was iso-
lated (0.206 g, 36%) as a colourless solid, mp¼85–87 ꢀC. 1H NMR
(DMSO-d6, 250 MHz):
d
¼2.08 (s, 3H, CH3), 2.21 (s, 3H, CH3), 7.27–
(CDCl3, 250 MHz):
d
¼2.23 (s, 3H, CH3), 3.36 (s, 3H, OCH3), 6.44 (d,
7.52 (m, 3H, CHAr), 7.74 (s, 1H, CHAr), 8.34 (d, 3J¼7.5 Hz, 1H, CHAr),
11.97 (br s, 1H, NH), 13.60 (s, 1H, OH). 13C NMR (DMSO-d6, 62 MHz):
dC¼10.6, 13.9 (CH3), 107.3 (CAr), 112.4, 116.4, 121.3, (CHAr), 123.0
(CAr), 123.2, 123.6, 129.2 (CHAr), 135.1, 148.3, 159.2, (CAr), 165.6
(C]O). MS (EI, 70 eV): m/z (%)¼239 ([M]þ, 89), 224 (34), 191 (10),
97 (26), 84 (100), 66 (98), 57 (95). Anal. Calcd for C15H13NO2: C
75.30, H 5.48, N 5.85; found: C 75.40, H 5.42, N 5.70.
4J¼1.6 Hz, 1H, CHAr), 6.77 (d, 4J¼1.3 Hz, 1H, CHAr), 7.25 (d, 3J¼8.8 Hz,
2H, CHAr), 8.10 (d, 3J¼8.8 Hz, 2H, CHAr), 10.81 (s, 1H, OH). 13C NMR
(CDCl3, 62 MHz): dC¼21.6 (CH3), 51.7 (OCH3), 108.6 (CAr), 118.2
(CHAr), 122.8 (2CHAr), 123.5 (CHAr), 129.0 (2CHAr), 142.1, 145.4, 146.9,
149.9, 162.2 (CAr), 170.0 (C]O). GC–MS (EI 70 eV): m/z (%)¼287
([M]þ, 27), 255 (100), 197 (9), 181 (30), 152 (20), 115 (5), 76 (7).
HRMS (EI): Calcd for C15H13NO5: 287.07882; found: 287.07879.
4.5.3. 8-Ethyl-7-hydroxy-9-methylphenanthridin-6(5H)-one
(7c). Starting with 6c (0.137 g, 0.4 mmol), 7c was isolated (0.070 g,
70%)bycolumnchromatography (silica gel, heptanes/EtOAc¼30:1/
20:1) as a colourless solid, mp¼257–259 ꢀC. 1H NMR (DMSO-d6,
4.4.23. Methyl 3-hydroxy-4,5-dimethyl-40-nitrobiphenyl-2-carboxy-
late (6w). Starting with 5b (0.598 g, 2.2 mmol), TiCl4 (0.413 g,
2.2 mmol), CH2Cl2 (4 mL) and 4h (0.558 g, 2.0 mmol), 6w was iso-
lated (0.276 g, 46%) as a colourless solid, mp¼87–89 ꢀC. 1H NMR
250 MHz):
d
¼1.10 (t, 3J¼8.0 Hz, 3H, CH3), 2.47 (s, 3H, CH3), 2.68 (q,
(CDCl3, 250 MHz):
d
¼2.16 (s, 3H, CH3), 2.25 (s, 3H, CH3) 3.40 (s, 3H,
3J¼7.5 Hz, 2H, CH2), 7.26–7.32 (m,1H, CHAr), 7.36–7.39 (m,1H, CHAr),
7.46–7.52 (m, 1H, CHAr), 7.75 (s, 1H, CHAr), 8.31 (d, 3J¼8.4 Hz, 1H,
CHAr), 11.99 (br s, 1H, NH), 13.59 (s, 1H, OH). 13C NMR (DMSO-d6,
62 MHz): dC¼13.0, 18.5 (CH3), 19.8 (CH2), 107.6 (CAr), 113.5, 116.5
(CHAr), 118.3 (CAr), 123.0, 123.3, (CHAr), 127.8 (CHAr), 129.3 (CHAr),
132.2, 135.2, 143.6, 158.9 (CAr), 165.8 (C]O). MS (EI, 70 eV): m/z
(%)¼253 ([M]þ, 39), 238 (100), 220 (2),190 (5),165 (6),104 (4), 95 (3),
63 (3). HRMS (EI): Calcd forC16H15NO2: 253.10973; found: 253.10991.
OCH3), 6.49 (s, 1H, CHAr), 7.29 (d, 3J¼8.8 Hz, 2H, CHAr), 8.14 (d,
3J¼8.8 Hz, 2H, CHAr), 11.18 (s, 1H, OH). 13C NMR (CDCl3, 62 MHz):
dC¼11.5, 20.4 (CH3), 51.7 (OCH3), 108.2 (CAr), 122.7 (2CHAr), 123.6
(CHAr), 125.4 (CHAr), 129.0 (2CHAr), 138.9, 143.5, 146.6, 150.2, 160.2
(CAr), 171.1 (C]O). GC–MS (EI 70 eV): m/z (%)¼301 ([M]þ, 40), 269
(100), 254 (19), 223 (42),195 (17),180 (6),165 (32),152 (29),139 (7),
115 (7), 76 (5). HRMS (EI): Calcd for C16H15NO5: 301.09447; found:
301.09477.
4.5.4. 7-Hydroxy-9-methyl-8-octylphenanthridin-6(5H)-one
(7d). Starting with 6d (0.275 g, 0.7 mmol), 7d was isolated (0.200 g,
69%) by column chromatography (silica gel, heptanes/
EtOAc¼30:1/20:1) as a colourless solid, mp¼268–269 ꢀC. 1H NMR
4.4.24. Ethyl 4-ethyl-3-hydroxy-5-methyl-40-nitrobiphenyl-2-carboxy-
late (6x). Starting with 5c (0.659 g, 2.2 mmol), TiCl4 (0.413 g,
2.2 mmol), CH2Cl2 (4 mL) and 4h (0.558 g, 2.0 mmol), 6x was iso-
lated (0.217 g, 33%) as a colourless solid, mp¼80–82 ꢀC. 1H NMR
(DMSO-d6/CDCl3, 250 MHz):
d
¼0.77–0.85 (m, 3H, CH3), 1.85–1.24
(CDCl3, 250 MHz):
d
¼0.65 (t, 3J¼7.4 Hz, 3H, CH3), 1.09 (t, 3J¼7.5 Hz,
(m, 8H, CH2), 1.41–1.49 (m, 4H, CH2), 2.41 (s, 3H, Ch3), 2.60–2.66 (m,
2H, CH2), 7.16–7.32 (m, 3H, CHAr), 7.53 (s,1H, CHAr), 8.12 (d, 3J¼7.8 Hz,
1H, CHAr),11.70 (br s, 1H, NH),13.44 (s,1H, OH). 13C NMR (DMSO-d6/
CDCl3, 62 MHz): dC¼13.8, 20.1 (CH3), 22.1, 25.3, 28.4, 28.6, 29.0, 29.3,
31.5 (CH2), 107.6 (CAr), 112.8, 112.9, 116.3 (CHAr), 118.2 (CAr), 122.6
(CHAr),126.6,126.7 (CAr),128.6 (CHAr),132.0,143.2,159.2 (CAr),165.6
(C]O). MS (EI, 70 eV): m/z (%)¼337 ([M]þ, 28), 308 (4), 276 (3), 252
(7), 238 (100), 224(5),192(3),160(4)128(25), 97(14), 69(15). HRMS
(EI): Calcd for C22H27NO2: 337.20363; found: 337.20310.
3H, CH3), 2.27 (s, 3H, CH3), 2.67 (q, 3J¼7.5 Hz, 2H, CH2), 3.92 (q,
3J¼7.4 Hz, 2H, OCH2), 6.46 (s, 1H, CHAr), 7.30 (d, 3J¼8.8 Hz, 2H,
CHAr), 8.14 (d, 3J¼8.8 Hz, 2H, CHAr), 11.27 (s, 1H, OH). 13C NMR
(CDCl3, 62 MHz): dC¼12.9, 13.1, 19.4 (CH3), 19.6 (CH2), 61.1 (OCH2),
108.5 (CAr), 122.7 (2CHAr), 123.7 (CHAr), 129.1 (2CHAr), 131.3, 139.1,
142.5, 146.5, 150.5, 160.2 (CAr), 170.7 (C]O). GC–MS (EI 70 eV): m/z
(%)¼329 ([M]þ, 58), 283 (100), 266 (50), 240 (46), 222 (9), 209 (13),
178 (10), 165 (56), 152 (19), 139 (8), 115 (7), 77 (4). HRMS (EI): Calcd
for C18H19NO5: 329.12577; found: 329.12590.
4.5.5. 9-Ethyl-7-hydroxyphenanthridin-6(5H)-one (7e). Starting with
6e (0.190 g, 0.6 mmol), 7e was isolated (0.113 g, 75%) by column
chromatography (silica gel, heptanes/EtOAc¼30:1/20:1) as a col-
ourless solid, mp¼260–261 ꢀC. 1H NMR (DMSO-d6, 250 MHz):
4.5. General procedure for the synthesis
of phenanthridinones 7a–s
To a stirred methanol suspension (25 mL) of Pd/C (10 mol %) was
added 6a–s (1.0 equiv). The mixture was set under a hydrogen at-
mosphere. After stirring for 48 h at 20 ꢀC, the reaction mixture was
filtered (Celite) and the filtrate was concentrated in vacuo. The
residue was purified by chromatography (silica gel, heptanes/
EtOAc¼2:1).
d
¼1.27 (t, 3J¼7.7 Hz, 3H, CH2CH3), 2.75 (q, 3J¼7.2 Hz, 2H, CH2CH3),
6.85 (br s, 1H, CHAr), 7.28–7.34 (m, 1H, CHAr), 7.38–7.41 (m, 1H,
CHAr), 7.49–7.55 (m, 1H, CHAr), 7.76 (br s, 1H, CHAr), 8.36 (d,
3J¼8.3 Hz, 1H, CHAr), 12.02 (br s, 1H, NH), 13.25 (s, 1H, OH). 13C NMR
(DMSO-d6, 62 MHz):
d
¼15.0 (CH3), 28.8 (CH2), 107.9 (CAr), 111.7
113.7,116.5 (CHAr),118.1 (CAr),123.0,123.7,129.6 (CHAr),135.2,135.5,
151.8, 161.5 (CAr), 165.4 (CO). IR (neat, cmꢁ1):
n
¼3172 (w), 3042 (w),
~
4.5.1. 7-Hydroxy-9-methyl-6(5H)-phenanthridinone (7a). Starting
with 6a (0.429 g, 1.6 mmol), 7a was isolated (0.215 g, 64%) by col-
umn chromatography (silica gel, heptanes/EtOAc¼30:1/20:1) as
a colourless solid, mp¼245–247 ꢀC. 1H NMR (DMSO-d6, 250 MHz):
2956 (m), 2928 (m), 2867 (m), 1650 (s), 1620 (m), 1594 (w), 1556
(m), 1462 (w), 1453 (m), 1430 (m), 1371 (w), 1347 (m), 1299 (m),
1224 (m), 1174 (m), 1128 (w), 1100 (w), 1058 (w), 1014 (m), 948 (w),
909 (w), 846 (m), 770 (w), 747 (s), 720 (m), 680 (m), 633 (m), 553
(m). MS (EI, 70 eV): m/z (%)¼240 ([M]þþ1, 17), 239 ([M]þ, 100), 238
(32), 207 (13),196 (11). HRMS (EI): Calcd for C15H13NO2: 239.09408;
found: 239.094189.
d
¼2.45 (s, 3H, CH3), 6.82 (s, 1H, CHAr), 7.27–7.30 (m, 1H, CHAr), 7.33–
7.41 (m, 1H, CHAr), 7.49–7.55 (m, 1H, CHAr), 7.76 (m, 1H, CHAr), 8.34
(d, 3J¼7.9 Hz, 1H, CHAr), 12.02 (br s, 1H, NH), 13.25 (s, 1H, OH). 13
C
NMR (DMSO-d6, 62 MHz): dC¼21.8 (CH3), 107.9 (CAr), 113.1 115.0,
116.6 (CHAr), 118.0 (CAr), 123.2, 123.6, 128.4 (CHAr), 129.8, 135.6,
146.0, 159.4 (CAr), 165.7 (C]O). MS (EI, 70 eV): m/z (%)¼225 ([M]þ,
4.5.6. 9-Ethyl-7-hydroxy-8-methylphenanthridin-6(5H)-one
(7f). Starting with 6f (0.228 g, 0.7 mmol), 7f was isolated (0.097 g,

A. Riahi et al. / Tetrahedron 65 (2009) 9300–9315
9309
53%) by column chromatography (silica gel, heptanes/
123.1, 123.3 (CHAr), 126.1 (CAr), 129.3 (CHAr), 132.4, 135.2, 149.5,
EtOAc¼30:1/20:1) as a colourless solid, mp¼265–267 ꢀC. 1H NMR
159.3 (CAr), 165.7 (CO). IR (neat, cmꢁ1):
n
¼3172 (w), 3062 (w), 3022
~
(DMSO-d6, 250 MHz):
d
¼1.14 (t, 3J¼7.0 Hz, 3H, CH2CH3), 2.18 (s, 3H,
(w), 2956 (m), 2926 (m), 2867 (m), 1717 (w), 1651 (s), 1623 (m),
1595 (m), 1554 (m), 1460 (w), 1455 (m), 1437 (m), 1370 (m), 1347
(m), 1300 (m), 1225 (m), 1180 (m), 1126 (w), 1098 (w), 1056 (w),
1015 (m), 948 (w), 908 (w), 845 (m), 770 (w), 747 (s), 720 (m), 682
(m), 635 (m), 552 (m). MS (EI, 70 eV): m/z (%)¼338 ([M]þþ1, 8), 337
([M]þ, 34), 308 (12), 266 (13), 254 (15), 253 (72), 252 (100), 237
(10), 209 (9), 208 (12), 207 (39), 191 (9), 44 (11). HRMS (EI): Calcd
for C22H27NO2: 337.20363; found: 337.203119.
CH3), 2.77 (q, 3J¼7.1 Hz, 2H, CH2CH3), 7.26–7.32 (m, 1H, CHAr), 7.36–
7.39 (m,1H, CHAr), 7.45–7.51 (m,1H, CHAr), 7.70 (s,1H, CHAr), 8.34 (d,
3J¼7.8 Hz, 1H, CHAr), 11.95 (br s, 1H, NH), 13.62 (s, 1H, OH). 13C NMR
(DMSO-d6, 62 MHz):
d¼13.8, 15.4 (CH3), 28.8 (CH2), 107.4 (CAr),
111.8, 116.4 (CHAr), 118.1 (CAr), 123.0, 123.3 (CHAr), 126.0 (CAr), 129.2
(CHAr), 132.4, 135.1, 149.5, 159.3, (CAr), 165.0 (CO). IR (neat, cmꢁ1):
~
n
¼3172 (w), 3041 (w), 2955 (m), 2930 (m), 2866 (m), 1651 (s), 1622
(m), 1590 (w), 1550 (m), 1457 (w), 1435 (m), 1369 (w), 1345 (m),
1300 (m), 1220 (m), 1170 (m), 1128 (w), 1098 (w), 1060 (w), 1012
(m), 945 (w), 908 (w), 845 (m), 770 (w), 746 (s), 719 (m), 682 (m),
633 (m), 552 (m). MS (EI, 70 eV): m/z (%)¼255 ([M]þþ2, 11), 254
([M]þþ1, 26), 253 ([M]þ, 100), 252 (45), 239 (10), 238 (13), 226 (10),
225 (18), 224 (24), 84 (10), 66 (18), 44 (35), 43 (12). Anal. Calcd for
C16H15NO2: C 75.30, H 5.48, N 5.85; found.: C 75.38, H 5.43, N 5.75.
4.5.10. 9-Ethyl-7-hydroxy-8-octylphenanthridin-6(5H)-one
(7j). Starting with 6j (0.347 g, 0.8 mmol), 7j was isolated (0.147 g,
50%) by column chromatography (silica gel, heptanes/
EtOAc¼30:1/20:1) as a colourless solid, mp¼241–243 ꢀC. 1H NMR
(DMSO-d6, 250 MHz):
d
¼0.85–0.87 (m, 3H, (CH2)7CH3), 1.08 (t,
3J¼7.1 Hz, 3H, CH2CH3), 1.24–1.27 (m, 12H, 6ꢂCH2), 2.60–2.67 (m,
2H, CH2), 2.78 (q, 3J¼7.4 Hz, 2H, CH2CH3), 7.26–7.32 (m, 1H, CHAr),
7.36–7.42 (m, 1H, CHAr), 7.46–7.49 (m, 1H, CHAr), 7.74 (s, 1H, CHAr),
8.33 (d, 3J¼7.7 Hz, 1H, CHAr), 11.96 (br s, 1H, NH), 13.62 (s, 1H, OH).
4.5.7. 8,9-Diethyl-7-hydroxyphenanthridin-6(5H)-one (7g). Starting
with 6g (0.171 g, 0.5 mmol), 7g was isolated (0.069 g, 52%) by col-
umn chromatography (silica gel, heptanes/EtOAc¼30:1/20:1) as
a colourless solid, mp¼242–244 ꢀC. 1H NMR (DMSO-d6, 250 MHz):
13C NMR (DMSO-d6, 62 MHz):
28.5, 28.6, 29.1, 29.3, 31.3 (CH2), 107.3 (CAr), 111.6, 116.4 (CHAr), 118.3
d
¼13.8, 15.3 (CH3), 22.0, 26.0, 26.8,
d
¼1.13 (t, 3J¼7.0 Hz, 3H, CH2CH3), 1.27 (t, 3J¼7.0 Hz, 3H, CH2CH3),
(CAr), 123.0, 123.3 (CHAr), 128.3 (CAr), 129.3 (CHAr), 132.3, 135.2,
150.0, 159.2 (CAr), 165.7 (CO). IR (neat, cmꢁ1):
~
n
¼3169 (w), 3082 (w),
2.66–2.74 (m, 2H, CH2CH3), 2.76–2.83 (m, 2H, CH2CH3), 7.26–7.29
(m, 1H, CHAr), 7.36–7.40 (m, 1H, CHAr), 7.44–7.49 (m, 1H, CHAr), 7.74
(s, 1H, CHAr), 8.34 (d, 3J¼7.8 Hz, 1H, CHAr), 11.96 (br s, 1H, NH), 13.62
3020 (w), 2963 (m), 2921 (m), 2875 (m), 1716 (w), 1650 (s), 1594
(m),1500 (m),1430 (m),1408 (s), 1372 (m), 1330 (m),1319 (m), 1295
(m), 1235 (m), 1194 (m), 1112 (w), 1091 (m), 1047 (w), 1008 (w), 940
(w), 912 (w), 853 (m), 810 (s), 798 (m), 750 (s), 698 (m), 687 (m),
639 (m), 592 (m), 529 (m). MS (EI, 70 eV): m/z (%)¼352 ([M]þþ1,
11), 351 ([M]þ, 49), 253 (88), 252 (100), 237 (8). HRMS (EI): Calcd
for C23H29NO2: 351.22063; found: 351.220119.
(s, 1H, OH). 13C NMR (DMSO-d6, 62 MHz):
d
¼15.4, 16.8 (CH3), 18.1,
26.0 (CH2), 107.4 (CAr), 111.9, 116.4 (CHAr), 118.3 (CAr), 123.0, 123.3
(CHAr), 128.2 (CAr), 129.2 (CHAr), 132.4, 135.1, 149.5, 159.2, (CAr),
165.7 (CO). IR (neat, cmꢁ1):
n
¼3173 (w), 3035 (w), 2953 (m), 2927
~
(m), 2865 (m),1651 (s),1628 (m),1592 (w),1562 (m),1460 (w),1455
(m), 1433 (m), 1370 (w), 1347 (m), 1297 (m), 1222 (m), 1170 (m),
1123 (w), 1115 (w), 1058 (w), 1012 (m), 945 (w), 909 (w), 845 (m),
768 (w), 745 (s), 723 (m), 678 (m), 630 (m), 552 (m). MS (EI, 70 eV):
m/z (%)¼267 ([M]þ, 41), 253 (17), 252 (100). HRMS (EI): Calcd for
C17H17NO2: 267.12538; found: 267.125175.
4.5.11. 7-Hydroxy-9-propylphenanthridin-6(5H)-one (7k). Starting
with 6k (0.563 g, 1.8 mmol), 7k was isolated (0.240 g, 56%) by col-
umn chromatography (silica gel, heptanes/EtOAc¼30:1/20:1) as
a colourless solid, mp¼240–241 ꢀC. 1H NMR (DMSO-d6, 250 MHz):
d
¼0.92 (t, 3J¼7.1 Hz, 3H, CH3), 1.63–1.72 (m, 2H, CH2), 2.68 (t,
4.5.8. 9-Ethyl-8-hexyl-7-hydroxyphenanthridin-6(5H)-one
(7h). Starting with 6h (0.255 g, 0.7 mmol), 7h was isolated (0.109 g,
51%) by column chromatography (silica gel, heptanes/
EtOAc¼30:1/20:1) as a colourless solid, mp¼230–232 ꢀC. 1H NMR
3J¼7.1 Hz, 2H, CH2), 6.81 (br s, 1H, CHAr), 7.25–7.29 (m, 1H, CHAr),
7.32–7.39 (m, 1H, CHAr), 7.47–7.53 (m, 1H, CHAr), 7.74 (br s, 1H,
CHAr), 8.35 (d, 3J¼7.7 Hz, 1H, CHAr), 12.01 (br s, 1H, NH), 13.25 (s, 1H,
OH). 13C NMR (DMSO-d6, 62 MHz): dC¼13.6 (CH3), 23.6, 38.6 (CH2),
107.9 (CAr), 112.3, 114.3, 116.5 (CHAr), 118.2 (CAr), 123.1, 123.7, 129.7
(CHAr), 135.2, 135.5, 150.2, 161.4 (CAr), 165.7 (C]O). MS (EI, 70 eV):
m/z (%)¼253 ([M]þ, 40), 225 (100), 196 (20), 177 (30), 149 (60), 115
(15), 89 (12), 69 (20), 44 (70), 43 (9). HRMS (EI): Calcd for
C16H15NO2: 253.10973; found: 253.10991.
(CD3OD, 250 MHz):
d
¼0.96–0.99 (m, 3H, (CH2)5CH3), 1.03–1.08 (m,
3H, CH2CH3), 1.34–1.41 (m, 8H, 4ꢂCH2), 2.87–2.95 (m, 4H, 2ꢂCH2),
7.24–7.30 (m, 1H, CHAr), 7.44–7.45 (m, 1H, CHAr), 7.48–7.51 (m, 1H,
CHAr), 7.74 (s, 1H, CHAr), 8.29 (d, 3J¼7.8 Hz, 1H, CHAr). 13C NMR
(CD3OD, 62 MHz):
d¼14.5, 15.4 (CH3), 23.5, 26.4, 27.1, 27.6, 29.8,
32.8 (CH2), 108.8 (CAr), 124.4, 117.0 (CHAr), 120.0 (CAr), 122.7, 124.1
(CHAr), 129.1 (CAr), 130.0 (CHAr), 134.0, 136.9, 151.0, 161.1, (CAr), 167.5
4.5.12. 7-Hydroxy-8-methyl-9-propylphenanthridin-6(5H)-one
(7l). Starting with 6l (0.480 g, 1.45 mmol), 7l was isolated (0.190 g,
50%) by column chromatography (silica gel, heptanes/
EtOAc¼30:1/20:1) as a colourless solid, mp¼245–247 ꢀC. 1H NMR
(CO). IR (neat, cmꢁ1):
n
¼2971 (m), 2910 (w), 2831 (m), 2758 (m),
~
2719 (m), 2487 (m), 2096 (w), 1586 (w), 1467 (m), 1397 (w), 1330
(w), 1202 (w), 1151 (m), 1103 (m), 978 (m), 957 (m), 840 (w), 805
(w), 612 (m). MS (EI, 70 eV): m/z (%)¼324 ([M]þþ1, 11), 323 ([M]þ,
31), 266 (11), 254 (19), 253 (78), 252 (100), 237 (10). HRMS (EI):
Calcd for C21H25NO2: 323.18798; found: 323.18.7220.
(DMSO-d6, 250 MHz):
d
¼0.90 (t, 3J¼7.4 Hz, 3H, CH3), 1.50–1.59 (m,
2H, CH2), 2.12 (s, 3H, CH3), 2.65 (t, 3J¼7.5 Hz, 2H, CH2), 7.18–7.24 (m,
1H, CHAr), 7.28–7.32 (m, 1H, CHAr), 7.32–7.43 (m, 1H, CHAr), 7.64 (s,
1H, CHAr), 8.25 (d, 3J¼8.2 Hz, 1H, CHAr), 11.89 (br s, 1H, NH), 13.55 (s,
1H, OH). 13C NMR (DMSO-d6, 62 MHz): dC¼10.5, 13.8 (CH3), 23.0,
35.9 (CH2), 107.4 (CAr), 112.3, 116.6 (CHAr), 118.5, 121.5 (CAr), 123.0,
123.3, 129.3 (CHAr), 131.9, 135.2, 148.6, 159.4 (CAr), 165.7 (C]O). MS
(EI, 70 eV): m/z (%)¼267 ([M]þ, 100), 252 (76), 239 (75), 224 (34),
210 (5), 190 (7), 165 (7), 78 (34), 63 (43), 43 (9). HRMS (EI): Calcd for
C17H17NO2: 267.12535; found: 267.12538.
4.5.9. 9-Ethyl-8-heptyl-7-hydroxyphenanthridin-6(5H)-one
(7i). Starting with 6i (0.265 g, 0.7 mmol), 7i was isolated (0.109 g,
49%) by column chromatography (silica gel, heptanes/
EtOAc¼30:1/20:1) as a colourless solid, mp¼232–234 ꢀC. 1H NMR
(DMSO-d6, 250 MHz):
d
¼0.85–0.86 (m, 3H, (CH2)6CH3), 1.10 (t,
3J¼7.1 Hz, 3H, CH2CH3), 1.26–1.29 (m, 10H, 5ꢂCH2), 2.63–2.72 (m,
2H, CH2), 2.78 (q, 3J¼7.7 Hz, 2H, CH2CH3), 7.23–7.29 (m, 1H, CHAr),
7.36–7.41 (m, 1H, CHAr), 7.46–7.52 (m, 1H, CHAr), 7.74 (s, 1H, CHAr),
8.34 (d, 3J¼7.7 Hz, 1H, CHAr), 11.94 (br s, 1H, NH), 13.63 (s, 1H, OH).
4.5.13. 8-Ethyl-7-hydroxy-9-propylphenanthridin-6(5H)-one
(7m). Starting with 6m (0.202 g, 0.6 mmol), 7m was isolated
(0.100 g, 63%) by column chromatography (silica gel, heptanes/
EtOAc¼30:1/20:1) as a colourless solid, mp¼232–234 ꢀC. 1H NMR
13C NMR (DMSO-d6, 62 MHz):
28.6, 29.1, 29.3, 31.3 (CH2), 107.4 (CAr), 111.8, 116.4 (CHAr), 118.3 (CAr),
d¼13.9, 15.4 (CH3), 22.0, 26.0, 28.5,

9310
A. Riahi et al. / Tetrahedron 65 (2009) 9300–9315
(DMSO-d6, 250 MHz):
d
¼1.00 (t, 3J¼8.1 Hz, 3H, CH3), 1.13 (t,
(s). MS (EI, 70 eV): m/z (%)¼282 ([M]þþ1, 12), 281 ([M]þ, 57), 252
(15), 240 (16), 239 (100), 238 (15), 224 (31). HRMS (EI): Calcd for
C18H19NO2: 281.14103; found: 281.141039.
3J¼7.2 Hz, 3H, CH3), 1.66 (q, 3J¼7.3 Hz, 2H, CH2), 2.66–2.77 (m, 4H,
CH2), 7.26–7.36 (m, 2H, CHAr), 7.49–7.58 (m, 2H, CHAr), 8.34 (d,
3J¼8.0 Hz, 1H, CHAr), 11.90 (br s, 1H, NH), 13.62 (s, 1H, OH). 13C NMR
(DMSO-d6, 62 MHz): dC¼13.9, 14.0 (CH3), 18.3, 24.0, 35.0 (CH2),
107.5 (CAr), 112.6, 116.6 (CHAr), 118.4, 121.6 (CAr), 123.0, 123.8, 131.3
(CHAr), 132.3, 135.2, 147.8, 159.2 (CAr), 165.7 (C]O). MS (EI, 70 eV):
m/z (%)¼281 ([M]þ, 100), 238 (76), 207 (12), 224 (30), 190 (7), 165
(5), 78 (40), 63 (23), 43 (8). HRMS (EI): Calcd for C17H17NO2:
267.12535; found: 267.12538. Anal. Calcd for C18H19NO2: C 76.84, H
6.81, N 4.98; found.: C 76.90, H 6.60, N 4.90.
4.5.17. 9-Butyl-8-hexyl-7-hydroxyphenantridin-6(5H)-one
(7q). Starting with 6q (0.098 g, 0.6 mmol), 7q was isolated (0.097 g,
50%) by column chromatography (silica gel, heptanes/
EtOAc¼30:1/20:1) as a colourless solid, mp¼220–222 ꢀC. 1H NMR
(DMSO-d6, 250 MHz):
d
¼0.84–0.90 (m, 3H, (CH2)5CH3),0.95 (t,
3J¼7.3 Hz, 3H, (CH2)3CH3), 1.22–1.31 (m, 6H, 3ꢂCH2), 1.37–1.43 (m,
4H, 2ꢂCH2), 1.57–1.64 (m, 2H, CH2), 2.63–2.77 (m, 4H, 2ꢂCH2),
7.26–7.32 (m, 1H, CHAr), 7.36–7.39 (m, 1H, CHAr), 7.46–7.51 (m, 1H,
CHAr), 7.73 (s, 1H, CHAr), 8.33 (d, 3J¼8.7 Hz, 1H, CHAr), 11.95 (br s, 1H,
4.5.14. 8-Hexyl-7-hydroxy-9-propylphenanthridin-6(5H)-one
(7n). Starting with 6n (0.250 g, 0.62 mmol), 7n was isolated
(0.150 g, 74%) by column chromatography (silica gel, heptanes/
EtOAc¼30:1/20:1) as a colourless solid, mp¼237–239 ꢀC. 1H NMR
NH), 13.63 (s, 1H, OH).13C NMR (DMSO-d6, 62 MHz):
d
¼13.7, 13.9
(CH3), 21.9, 22.2, 24.9, 28.9, 30.6, 31.0, 32.7, 33.0 (CH2), 107.4 (CAr),
112.5, 116.4 (CHAr), 118.3 (CAr), 121.3, 123.3 (CHAr), 126.2 (CAr), 129.2
(CHAr), 132.3, 135.1, 148.2, 159.3 (CAr) 165.7 (CO). IR (neat, cmꢁ1):
~
(CDCl3, 250 MHz):
d
¼0.83 (t, 3J¼7.8 Hz, 3H, CH3), 0.99 (t, 3J¼7.5 Hz,
3H, CH3), 1.26–1.48 (m, 8H, CH2), 1.60–1.69 (m, 2H, CH2), 2.66–2.72
(m, 4H, CH2), 7.11–7.15 (m, 1H, CHAr), 7.21–7.25 (m, 1H, CHAr), 7.37–
7.40 (m, 1H, CHAr), 7.48 (s, 1H, CHAr), 8.10 (d, 3J¼8.5 Hz, 1H, CHAr),
9.49 (br s, 1H, NH), 13.92 (s, 1H, OH). 13C NMR (CDCl3, 75 MHz):
dC¼14.1, 14.2 (CH3), 22.6, 24.4, 25.8, 29.5, 29.8, 31.7, 36.0 (CH2), 107.5
(CAr), 112.0, 112.6, 116.2 (CHAr), 119.4 (CAr), 123.2 (CHAr), 123.5 (CAr),
127.9 (CHAr), 129.1, 131.4, 133.5, 148.7 (CAr), 160.0 (C]O). MS (EI
70 eV): m/z (%)¼337 ([M]þ, 42), 280 (9), 266 (100), 225 (19), 161 (9),
128 (40), 83 (24), 69 (43) 43 (9). HRMS (EI): Calcd for C22H27NO2:
337.20363; found: 337.20310.
n
¼3166 (w), 2951 (m), 2923 (m), 2867 (m), 1714 (w), 1650 (s), 1626
(m), 1597 (m), 1551 (w), 1502 (m), 1454 (w), 1409 (m), 1376 (w),
1349 (m), 1309 (m), 1267 (m), 1233 (m), 1195 (m), 1101 (w), 1041
(w), 1014 (w), 937 (w), 872 (m), 845 (m), 809 (m), 786 (s), 747 (s),
729 (m), 672 (m), 659 (m), 621 (w), 559 (m), 535 (w). MS (EI, 70 eV):
m/z (%)¼352 ([M]þþ1, 27), 351 ([M]þ, 90), 322 (17), 294 (29), 281
(42), 280 (86), 266 (13), 252 (18), 250 (18), 240 (18), 239 (87), 238
(100), 226 (11), 225 (13), 224 (12), 210 (15), 63 (13). HRMS (EI):
Calcd for C23H29NO2: 351.21958; found: 351.219174.
4.5.18. 9-Ethyl-8-hexyl-7-hydroxy-10-methylphenanthridin-6(5H)-
one (7r). Starting with 6r (0.199 g, 0.5 mmol), 7r was isolated
(0.084 g, 50%) by column chromatography (silica gel, heptanes/
EtOAc¼30:1/20:1) as a colourless solid, mp¼193–194 ꢀC. 1H NMR
4.5.15. 9-Butyl-7-hydroxyphenanthridin-6(5H)-one (7o). Starting
with 6o (0.164 g, 0.5 mmol), 7o was isolated (0.931 g, 70%) by col-
umn chromatography (silica gel, heptanes/EtOAc¼30:1/20:1) as
a colourless solid, mp¼234–235 ꢀC. 1H NMR (DMSO-d6, 250 MHz):
(DMSO-d6, 250 MHz):
d
¼0.87 (t, 3J¼6.5 Hz, 3H, CH2CH3), 1.16 (t,
d
¼0.92 (t, 3J¼7.1 Hz, 3H, (CH2)3CH3), 1.27–1.41 (m, 2H, CH2), 1.59–
3J¼7.1 Hz, 3H, (CH2)5CH3), 1.25–1.36 (m, 6H, 3ꢂCH2), 2.50 (s, 3H,
CH3), 2.67–2.73 (m, 4H, 2ꢂCH2), 2.82 (q, 3J¼7.7 Hz, 2H, CH2CH3),
7.23–7.29 (m, 1H, CHAr), 7.38–7.41 (m, 1H, CHAr), 7.43–7.49 (m, 1H,
CHAr), 8.23 (d, 3J¼8.0 Hz, 1H, CHAr), 11.93 (br s, 1H, NH), 13.95 (s, 1H,
1.71 (m, 2H, CH2), 2.71 (t, 3J¼7.6 Hz, 2H, CH2(CH2)2CH3), 6.83 (s, 1H,
CHAr), 7.28–7.33 (m, 1H, CHAr), 7.38–7.41 (m, 1H, CHAr), 7.49–7.55
(m, 1H, CHAr), 7.75 (s, 1H, CHAr), 8.35 (d, 3J¼8.8 Hz, 1H, CHAr), 12.02
(br s, 1H, NH), 13.26 (s, 1H, OH). 13C NMR (DMSO-d6, 62 MHz):
OH). 13C NMR (DMSO-d6, 62 MHz):
23.2, 25.5, 29.0, 29.3, 31.1 (CH2), 108.1 (CAr), 116.1 (CHAr) 119.3 (CAr),
d
¼13.8, 14.1, 19.5 (CH3), 22.0,
d
¼13.7 (CH3), 21.7, 32.6, 35.5 (CH2), 107.9 (CAr), 112.2, 114.2, 116.5
(CHAr), 118.2 (CAr), 123.0, 123.7, 129.7 (CHAr), 135.1, 135.5, 150.5,
121.8 (CHAr), 122.1, 126.6 (CAr), 128.3, 128.4 (CHAr), 132.1, 135.8,
161.5 (CAr) 165.4 (CO). IR (neat, cmꢁ1):
n
¼3170 (w), 3075 (w), 3012
149.0, 157.7 (CAr), 166.1 (CO). IR (neat, cmꢁ1):
~
~
n
¼3305 (w), 3169 (w),
(w), 2953 (m), 2923 (m), 2856 (m), 1659 (s), 1626 (m), 1595 (m),
1552 (m), 1503 (m), 1455 (w), 1426 (m), 1406 (m), 1378 (m), 1349
(m), 1296 (m), 1229 (m), 1163 (m), 1126 (w), 1078 (w), 1037 (w),
1006 (m), 938 (w), 916 (w), 862 (m), 805 (m), 774 (m), 747 (s), 680
(m), 639 (m), 617 (m), 553 (m). MS (EI, 70 eV): m/z (%)¼268
([M]þþ1, 8), 267 ([M]þ, 53), 226 (24), 225 (100), 224 (23), 196 (10),
178 (8), 78 (24), 63 (26), 44 (10). HRMS (EI): Calcd for C17H17NO2:
267.12538; found: 267.125349.
3033 (w), 2955 (m), 2921 (m), 2856 (m), 1722 (w), 1656 (m), 1586
(m),1549 (m),1503 (m),1465 (m),1408 (s),1376 (m),1344 (m),1291
(m), 1275 (m), 1261 (m), 1180 (m), 1164 (m), 1128 (m), 1113 (m), 1011
(m), 981 (w), 945 (w), 911 (m), 857 (m), 810 (s), 751 (m), 720 (m),
692 (m), 665 (m), 634 (w), 591 (m), 556 (m), 538 (m). MS (EI,
70 eV): m/z (%)¼338 ([M]þþ1, 25), 337 ([M]þ, 84), 308 (10), 280
(15), 267 (86), 266 (100), 250 (14), 238 (12), 237 (12). HRMS (EI):
Calcd for C22H27NO2: 337.20363; found: 337.203114.
4.5.16. 9-Butyl-7-hydroxy-8-methylphenanthridin-6(5H)-one
(7p). Starting with 6p (0.171 g, 0.5 mmol), 7p was isolated (0.076 g,
54%) by column chromatography (silica gel, heptanes/
EtOAc¼30:1/20:1) as a colourless solid, mp¼257–259 ꢀC. 1H NMR
4.5.19. 10-Chloro-7-hydroxy-9-propylphenanthridin-6(5H)-one
(7s). Starting with 6s (0.174 g, 0.5 mmol), 7s was isolated (0.070 g,
49%) by column chromatography (silica gel, heptanes/
EtOAc¼30:1/20:1) as a colourless solid, mp¼258–260 ꢀC. 1H NMR
(DMSO-d6, 250 MHz):
d
¼0.94 (t, 3J¼7.1 Hz, 3H, (CH2)3CH3), 1.36–
(DMSO-d6, 250 MHz):
d
¼0.99 (t, 3J¼8.1 Hz, 3H, CH3), 1.62–1.71 (m,
1.44 (m, 2H, CH2), 1.52–1.61 (m, 2H, CH2), 2.20 (s, 3H, CH3), 2.76 (t,
3J¼7.4 Hz, 2H, CH2(CH2)2CH3), 7.26–7.32 (m, 1H, CHAr), 7.36–7.39
(m, 1H, CHAr), 7.46–7.52 (m, 1H, CHAr), 7.73 (s, 1H, CHAr), 8.34 (d,
3J¼8.1 Hz, 1H, CHAr), 11.96 (br s, 1H, NH), 13.62 (s, 1H, OH). 13C NMR
2H, CH2CH2CH3), 2.82 (t, 3J¼7.4 Hz, 2H, CH2CH2CH3), 7.02 (s, 1H,
CHAr), 7.28–7.34 (m, 1H, CHAr), 7.42–7.46 (m, 1H, CHAr), 7.54–7.60
(m, 1H, CHAr), 9.35 (d, 3J¼8.7 Hz, 1H, CHAr), 12.27 (br s, 1H, NH),
14.00 (s, 1H, OH). 13C NMR (DMSO-d6, 62 MHz):
36.7 (CH2), 110.1 (CAr), 116.7, 117.0 (CHAr) 117.5, 118.6 (CAr), 122.3,
d
¼13.7 (CH3), 22.1,
(DMSO-d6, 62 MHz):
d
¼10.6, 13.7 (CH3), 22.1, 31.9, 33.5 (CH2), 107.3
(CAr), 112.4, 116.4 (CHAr), 118.3, 121.3 (CAr), 123.0, 123.3, 129.2 (CHAr),
127.3, 130.0 (CHAr), 131.9, 136.2, 149.1, 160.4 (CAr), 165.0 (CO). IR
132.1, 135.1, 148.6, 159.2 (CAr) 165.6 (CO). IR (neat, cmꢁ1):
n
¼3305
(neat, cmꢁ1):
n
¼3116 (w), 3129 (w), 3078 (w), 3014 (w), 2957 (m),
~
~
(w), 3169 (w), 3017 (w), 2953 (m), 2932 (m), 2860 (m), 1731 (w),
1657 (s), 1651 (s), 1632 (m), 1595 (m), 1553 (m), 1503 (m), 1449 (w),
1409 (m), 1372 (m), 1348 (m), 1304 (m), 1268 (m), 1236 (m), 1195
(m), 1113 (m), 1098 (m), 1057 (m), 935 (m), 857 (m), 843 (m), 805
(s), 789 (s), 743 (s), 713 (m), 668 (m), 629 (m), 620 (m), 560 (s), 539
2933 (m), 2868 (m), 2743 (m), 1656 (s), 1610 (m), 1580 (m), 1552
(m), 1503 (m), 1465 (m), 1408 (s), 1338 (m), 1290 (m), 1275 (m),
1242 (m), 1190 (m),1174 (m),1134 (m),1090 (m),1040 (w),1018 (w),
944 (w), 923 (w), 872 (m), 850 (m), 808 (s), 784 (m), 772 (m), 755
(s), 711 (s), 661 (m), 627 (m), 610 (w), 598 (m), 548 (m). MS (EI,

A. Riahi et al. / Tetrahedron 65 (2009) 9300–9315
9311
70 eV): m/z (%)¼289 ([Mþ] 37Cl, 27), 287 ([Mþ] 35Cl, 88), 261 (30),
260 (15), 259 (100), 253 (12), 252 (31), 225 (40), 224 (40), 211 (10),
196 (20), 178 (10), 177 (11), 84 (12), 78 (70), 66 (11), 63 (78), 61 (13),
45 (10), 44 (12). HRMS (EI): Calcd for C16H14NO2Cl: 287.07076;
found: 287.070305.
(19), 29 (11). HRMS (EI): Calcd for C11H11NO4: 221.06826; found:
221.068910.
4.7.2. 3-Ethoxy-2-nitro-1-o-tolylprop-2-en-1-one (12b). Starting
with 11b (2.5 g, 14.0 mmol), triethyl orthoformate (3.00 g,
18.9 mmol) and acetic anhydride (5.00 g., 31.65 mmol), 12b was
4.6. General procedure for the synthesis of aminobiaryls 8a,b
isolated as a red oil (2.69 g, 82%). 1H NMR (300 MHz, CDCl3):
d¼1.29
(t, 3J¼7.1 Hz, 3H, OCH2CH3), 2.33 (s, 3H, CH3), 4.20 (q, 3J¼7.0 Hz, 2H,
To a stirred methanol suspension (25 mL) of Pd/C (10 mol %) was
added 6t,u (1.0 equiv). The mixture was set under a hydrogen at-
mosphere. After stirring for 48 h at 20 ꢀC, the reaction mixture was
filtered (Celite) and the filtrate was concentrated in vacuo. The
residue was purified by chromatography (silica gel, heptanes/
EtOAc¼2:1).
OCH2CH3), 7.15–7.18 (m, 2H, CHAr), 7.31–7.39 (m, 2H, CHAr), 8.23 (s,
1H, CHOlf). 13C NMR (75 MHz, CDCl3):
d
¼15.1, 20.8 (CH3), 74.3
(OCH2), 121.8 (C), 125.7, 127.0, 131.0, 133.0 (CHAr), 136.9, 139.6 (CAr),
161.6 (CHOlf), 187.2 (CO). IR (neat, cmꢁ1):
n
¼3064 (w), 2927 (w),
~
1698 (m), 1634 (m), 1561 (m), 1532 (m), 1456 (m), 1367 (m), 1300
(m), 1219 (s), 1163 (m), 1094 (m), 1002 (m), 909 (m), 873 (m), 839
(w), 796 (w), 731 (s), 696 (w), 649 (m).
4.6.1. Methyl 30-amino-3-hydroxy-4,5-dimethylbiphenyl-2-carboxyl-
ate (8a). Starting with 6t (0.150 g, 0.5 mmol), 8a was isolated
(0.110 g, 81%) by column chromatography (silica gel, heptanes/
EtOAc¼30:1/20:1) as a colourless solid, mp¼140–141 ꢀC. 1H NMR
4.7.3. 1-(2-Chlorophenyl)-3-ethoxy-2-nitroprop-2-en-1-one
(12c). Starting with 11c (2.0 g, 10.0 mmol), triethyl orthoformate
(2.4 g,1.51 mmol) and acetic anhydride (4.0 g., 25.30 mmol),12c was
isolated as a reddish viscous oil (2.0 g, 81%). 1H NMR (300 MHz,
(CDCl3, 250 MHz):
d
¼2.13 (s, 3H, CH3), 2.21 (s, 3H, CH3), 3.41 (br m,
2H, NH2), 3.44 (s, 3H, OCH3), 6.40 (s, 1H, CHAr), 6.49–6.57 (m, 3H,
CHAr), 7.00–7.06 (m, 1H, CHAr), 10.86 (s, 1H, OH). 13C NMR (CDCl3,
62 MHz): dC¼11.4, 20.4 (CH3), 51.6 (OCH3), 109.1 (CAr), 113.3, 114.9,
119.0 (CHAr), 123.6 (CAr), 123.8, 128.3, (CHAr), 141.6, 142.8, 144.2,
145.7, 159.2 (CAr), 172.0 (C]O). GC–MS (EI, 70 eV): m/z (%)¼271
([M]þ, 72), 239 (100), 224 (87), 210 (13), 196 (21), 180 (6), 167 (13),
135 (5), 115 (5), 98 (6), 65 (4). HRMS (EI): Calcd for C16H17NO3:
271.12029; found: 271.12050.
CDCl3):
d
¼1.30 (t, 3J¼7.0 Hz, 3H, OCH2CH3), 4.27 (q, 3J¼6.9 Hz, 2H,
OCH2CH3), 7.29–7.30 (m,1H, CHAr), 7.34–7.35 (m, 2H, CHAr), 7.49–7.51
(m, 1H, CHAr), 8.29 (s, 1H, CHOlf). 13C NMR (75 MHz, CDCl3):
d¼15.1
(CH3), 75.1 (OCH2), 126.6 (C), 128.9, 130.1, 131.9 (CHAr), 132.3 (CAr),
132.4 (CHAr), 136.4 (CAr), 160.0 (CHOlf), 184.2 (CO). IR (neat, cmꢁ1):
~
n
¼3068 (w), 2930 (w), 1777 (w), 1683 (m), 1587 (m), 1560 (s), 1523
(m),1470 (m),1368 (m),1319 (m),1212 (m),1163 (m),1064 (m),1037
(m), 917 (m), 816 (m), 739 (s), 684 (m), 606 (m), 583 (w), 549 (w).
4.6.2. Ethyl 30-amino-4-ethyl-3-hydroxy-5-methylbiphenyl-2-carb-
oxylate (8b). Starting with 6u (0.250 g, 0.8 mmol), 8b was isolated
(0.184 g, 78%) by column chromatography (silica gel, heptanes/
EtOAc¼30:1/20:1) as a colourless solid, mp¼145–147 ꢀC. 1H NMR
4.8. General procedure for the synthesis
of 4-nitrophenols 13a–i
To a CH2Cl2 solution (2 mL/1 mmol of 12a–c) of 12a–c was
added 5 (1.65 mmol) and, subsequently, TiCl4 (1.1 mmol) at ꢁ78 ꢀC.
The temperature of the solution was allowed to warm to 20 ꢀC
during 18 h with stirring. To the solution was added hydrochloric
acid (10%, 20 mL) and the organic and the aqueous layer were
separated. The latter was extracted with CH2Cl2 (3ꢂ20 mL). The
combined organic layers were dried (Na2SO4), filtered and the fil-
trate was concentrated in vacuo. The residue was purified by
chromatography (silica gel, n-heptanes/EtOAc) to give 13a–i.
(CDCl3, 300 MHz):
d
¼0.74 (t, 3J¼7.4 Hz, 3H, CH3), 1.07 (t, 3J¼7.5 Hz,
3H, CH3), 2.21 (s, 3H, CH3), 2.63 (q, 3J¼7.4 Hz, 2H, CH2), 3.42–3.60
(br m, 2H, NH2), 3.93 (q, 3J¼7.5 Hz, 2H, OCH2), 6.44–6.48 (m, 1H,
CHAr), 6.49–6.54 (m, 3H, CHAr), 6.96–7.03 (m, 1H, CHAr), 10.95 (s, 1H,
OH). 13C NMR (CDCl3, 75 MHz): dC¼13.1, 13.2, 19.4 (CH3), 19.6 (CH2),
60.7 (OCH2),109.0 (CAr),113.2,115.1,119.0,123.9, 128.3 (CHAr),129.6,
141.8, 141.9, 144.4, 145.7, 159.3 (CAr), 171.5 (C]O). GC–MS (EI,
70 eV): m/z (%)¼299 ([M]þ, 96), 253 (64), 238 (100), 220 (34), 210
(16), 180 (15), 152 (7), 128 (5), 90 (7), 65 (3). HRMS (EI): Calcd for
C18H21NO3: 299.15160; found: 299.15146.
4.8.1. Methyl 3-hydroxy-6-nitrobiphenyl-2-carboxylate (13a). Re-
action starting with 12a (0.331 g, 1.5 mmol) and 5a (0.429 g,
1.7 mmol), 13a was isolated after chromatography (silica gel, hep-
tanes/EtOAc) as a yellowish solid (0.230 g, 56%), mp¼137–138 ꢀC.
4.7. General procedure for the synthesis of 3-ethoxy-2-nitro-
1-phenylprop-2-en-1-ones 12a–c
1H NMR (300 MHz, CDCl3):
d
¼3.35 (s, 3H, OCH3), 7.02 (d, 3J¼9.0 Hz,
To a solution of 11a–c in acetic anhydride (1.0 equiv/1.0 equiv of
11a–c) was added triethyl orthoformate (1.2 equiv). The solution
was stirred at 120 ꢀC for 6 h. The solvent was concentrated in vacuo
and the residue was purified by chromatography (silica gel, hep-
tanes/EtOAc) to give 12a–c.
1H, CHAr), 7.07–7.10 (m, 2H, CHPh), 7.27–7.31 (m, 3H, CHPh), 7.82 (d,
3J¼8.9 Hz, 1H, CHAr), 11.07 (s, 1H, OH). 13C NMR (CDCl3, 75 MHz):
d
¼52.5 (OCH3), 113.6 (CCOOCH3), 117.7, 127.7, 127.7, 127.7, 127.8,
127.8, 128.5 (CHAr), 133.7, 136.2, 139.0 (CAr), 163.8 (COH), 170.2 (CO).
IR (KBr, cmꢁ1):
n
¼3086 (w), 3062 (w), 2954 (w), 1735 (w), 1670 (m),
~
1599 (w), 1576 (w), 1525 (m), 1501 (w), 1442 (m), 1324 (m), 1220
(m), 1156 (w), 1132 (m), 1095 (w), 1074 (w), 1026 (w), 970 (w), 907
(m), 837 (w), 813 (w), 769 (w), 727 (s), 698 (m), 672 (m), 648 (w),
584 (w). GC–MS (EI, 70 eV): m/z (%)¼273 ([M]þ, 80), 242 (17), 241
(100), 224 (15), 213 (25), 212 (13), 196 (14), 185 (18), 184 (11), 183
(13), 159 (16), 157 (11), 155 (20), 140 (15), 139 (66), 138 (10), 129
(25), 128 (14), 127 (19), 115 (10), 113 (10), 102 (10), 77 (12), 63 (11).
HRMS (EI): Calcd for C14H11O5N ([M]þ): 273.06317; found:
273.063020.
4.7.1. 3-Ethoxy-2-nitro-1-phenylprop-2-en-1-one (12a). Starting with
11a (3.50 g, 21.2 mmol), triethyl orthoformate (4.20 g, 26.5 mmol)
and acetic anhydride (7.00 g, 44.3 mmol), 12a was isolated as
a reddish viscous oil (3.75 g, 80%). 1H NMR (300 MHz, CDCl3):
d
¼1.27 (t, 3J¼7.0 Hz, 3H, OCH2CH3), 4.20 (q, 3J¼6.9 Hz, 2H,
OCH2CH3), 7.37–7.42 (m, 3H, CHAr), 7.76–7.79 (m, 2H, CHAr), 8.28 (s,
1H, CHOlf). 13C NMR (75 MHz, CDCl3):
d
¼15.1 (CH3), 74.2 (OCH2),
128.1 (C), 128.8 (2ꢂCHAr), 129.0 (2ꢂCHAr), 134.1 (CHAr), 135.9 (CAr),
164.1 (CHOlf), 185.3 (CO). IR (neat, cmꢁ1):
n
¼3063 (w), 2935 (w),
~
1778 (w), 1674 (m), 1597 (w), 1562 (w), 1535 (m), 1500 (m), 1449
(w), 1338 (w), 1300 (m), 1222 (m), 1153 (w), 1124 (w), 1001 (w), 908
(m), 873 (w), 728 (s), 689 (m), 648 (w). MS (EI 70 eV): m/z (%)¼221
([M]þ, 8), 128 (12), 105 (100), 100 (41), 94 (16), 7 (70), 72 (17), 51
4.8.2. Methyl 3-hydroxy-4-methyl-6-nitrobiphenyl-2-carboxylate
(13b). Starting with 12a (0.331 g, 1.5 mmol) and 5b (0.457 g,
1.65 mmol), 13b was isolated after chromatography (silica gel,
heptanes/EtOAc) as a yellowish solid (0.245 g, 57%), mp¼57–59 ꢀC.

9312
A. Riahi et al. / Tetrahedron 65 (2009) 9300–9315
1H NMR (300 MHz, CDCl3):
d
¼2.28 (s, 3H, CH3), 3.33 (s, 3H, OCH3),
(s), 669 (m), 612 (w). GC–MS (EI, 70 eV): m/z (%)¼385 ([M]þ, 64),
337 (23), 336 (95), 255 (16), 254 (15), 239 (21), 238 (100), 209 (12),
208 (29), 180 (10), 152 (16). HRMS (EI): Calcd for C12H27O5N ([M]þ):
385.18837; found: 385.188315.
7.05–7.08 (m, 2H, CHPh), 7.26–7.29 (m, 3H, CHPh), 7.71 (s, 1H, CHAr),
11.33 (s, 1H, OH). 13C NMR (CDCl3, 75 MHz):
d
¼15.9 (CH3), 52.4
(OCH3), 112.6 (CCOOCH3), 127.6 (CHAr), 127.7 (2ꢂCHAr), 127.9
(3ꢂCHAr), 133.2, 136.3, 136.6, 142.6 (CAr), 162.3 (COH), 170.8 (CO). IR
(KBr, cmꢁ1):
4.8.6. Methyl
3-hydroxy-20-methyl-6-nitrobiphenyl-2-carboxylate
~
n
¼3062 (w), 2958 (w), 1737 (w), 1665 (m), 1574 (w),
1526 (m), 1495 (w), 1441 (m), 1373 (m), 1302 (m), 1251 (m), 1200
(m), 1170 (m), 1129 (m), 1070 (m), 1031 (w), 1001 (w), 983 (w), 902
(w), 864 (w), 812 (w), 778 (m), 727 (m), 696 (m), 663 (m), 610 (m),
574 (m). GC–MS (EI, 70 eV): m/z (%)¼287 ([M]þ, 80), 256 (17), 255
(100), 239 (15), 238 (75), 209 (15), 208 (76), 180 (10), 129 (14), 127
(10), 115 (14), 77 (10). HRMS (EI): Calcd for C15H13O5N ([M]þ):
287.07882; found: 287.078935.
(13f). Starting with 12b (0.352 g, 1.5 mmol) and 5a (0.429 g,
1.7 mmol), 13f was isolated after chromatography (silica gel, hep-
tanes/EtOAc) as a yellowish solid (0.292 g, 68%), mp¼74–76 ꢀC. 1H
NMR (300 MHz, CDCl3):
d
¼2.51 (s, 3H, CH3), 3.28 (s, 3H, OCH3), 6.96
(d, 3J¼8.4 Hz, 1H, CHAr), 7.11–7.15 (m, 3H, CHAr), 7.28–7.33 (m, 1H,
CHAr), 7.93 (d, 3J¼8.4 Hz, 1H, CHAr), 11.33 (s, 1H, OH). 13C NMR
(CDCl3, 75 MHz):
d
¼19.8 (CH3), 52.6 (OCH3), 113.1 (CCOOCH3), 117.9,
125.2 (CHAr), 128.3 (2ꢂCHAr), 129.1, 130.0 (CHAr), 132.9, 135.9, 139.0,
141.3 (CAr), 164.4 (COH), 170.2 (CO). IR (KBr, cmꢁ1):
n
¼3063 (w),
~
4.8.3. Ethyl 4-ethyl-3-hydroxy-6-nitrobiphenyl-2-carboxylate (13c). Star-
ting with 12a (0.331 g, 1.5 mmol) and 5c (0.499 g, 1.65 mmol), 13c
was isolated after chromatography (silica gel, heptanes/EtOAc) as
a viscous yellowish oil (0.306 g, 65%). 1H NMR (300 MHz, CDCl3):
2954 (w), 2649 (w), 1673 (m), 1598 (m), 1575 (m), 1518 (m), 1490
(m), 1441 (m), 1313 (s), 1313 (s), 1268 (m), 1232 (s), 1221 (s), 1173
(m), 1132 (m), 1086 (m), 1052 (m), 1034 (w), 964 (m), 912 (m), 832
(m), 814 (m), 763 (m), 733 (s), 689 (m), 658 (m), 593 (m), 531 (m).
GC–MS (EI, 70 eV): m/z (%)¼287 ([M]þ, 27), 270 (14), 269 (15), 256
(17), 239 (19), 238 (100), 237 (21), 228 (52), 226 (14), 181 (15), 153
(25), 127 (13), 115 (20), 63 (9). HRMS (EI): Calcd for C15H13O5N
([M]þ): 287.07882; found: 287.078912.
d
¼0.52 (t, 3J¼7.6 Hz, 3H, CH2CH3), 1.12 (t, 3J¼7.5 Hz, 3H, OCH2CH3),
2.59 (q, 3J¼7.5 Hz, 2H, CH2CH3), 3.75 (q, 3J¼7.5 Hz, 2H, OCH2CH3),
6.96–7.0 (m, 2H, CHPh), 7.16–7.18 (m, 3H, CHPh), 7.61 (s, 1H, CHAr),
11.42 (s, 1H, OH). 13C NMR (CDCl3, 75 MHz):
d
¼12.8, 13.0 (CH3),
22.8, 61.8 (CH2), 112.8 (CCOOCH3), 127.6 (CHAr), 127.7 (2ꢂCHAr),
128.1 (3ꢂCHAr), 133.3, 136.2, 136.8, 142.8 (CAr), 162.2 (COH), 170.4
(CO). IR (neat, cmꢁ1):
4.8.7. Methyl 3-hydroxy-20,4-dimethyl-6-nitrobiphenyl-2-carboxy-
late (13g). Starting with 12b (0.352 g, 1.5 mmol) and 5b (0.457 g,
1.7 mmol), 13g was isolated after chromatography (silica gel, hep-
tanes/EtOAc) as a yellowish solid (0.324 g, 72%), mp¼70–72 ꢀC. 1H
~
n
¼3083 (w), 3002 (w), 2963 (w), 1737 (w),
1657 (m), 1600 (w), 1567 (w), 1512 (m), 1443 (m), 1329 (m), 1298
(m), 1241 (m), 1191 (s), 1149 (m), 1063 (m), 1018 (m), 968 (w), 900
(m), 822 (m), 803 (m), 733 (s), 695 (s), 668 (s), 621 (m), 581 (m),
524 (m). GC–MS (EI, 70 eV): m/z (%)¼315 ([M]þ, 54), 270 (10), 269
(50), 253 (19), 252 (100), 223 (18), 222 (89), 165 (22), 152 (21), 129
(8). HRMS (EI): Calcd for C17H17O5N ([M]þ): 315.11012; found:
315.110219.
NMR (300 MHz, CDCl3):
d
¼1.99 (s, 3H, CH3), 2.29 (s, 3H, CH3), 3.34
(s, 3H, OCH3), 6.82–6.84 (m, 1H, CHAr), 7.03–7.16 (m, 3H, CHAr), 7.79
(s, 1H, CHAr), 11.63 (s, 1H, OH). 13C NMR (CDCl3, 75 MHz):
d
¼15.9,
19.9 (CH3), 52.6 (OCH3), 112.2 (CCOOCH3), 125.2, 127.3 (CHAr), 127.7
(CAr), 128.8, 129.0, 130.1 (CHAr), 136.0, 136.2, 136.3, 142.3 (CAr), 163.0
~
4.8.4. Methyl 4-butyl-3-hydroxy-6-nitrobiphenyl-2-carboxylate
(13d). Reaction starting with 12a (0.331 g, 1.5 mmol) and 5k
(0.522 g, 1.7 mmol), 13d was isolated after chromatography (silica
gel, heptanes/EtOAc) as a viscous yellowish oil (0.285 g, 58%). 1H
(COH), 170.8 (CO). IR (KBr, cmꢁ1):
n
¼3061 (w), 2953 (w), 2854 (w),
1664 (m), 1573 (m), 1523 (m), 1494 (w), 1380 (m), 1334 (s), 1285
(m), 1254 (s), 1202 (s), 1166 (m), 1133 (m), 1133 (m), 1104 (m), 1041
(w), 1018 (m), 964 (m), 899 (m), 871 (w), 813 (m), 753 (m), 723 (s),
661 (m), 589 (m), 531 (m). GC–MS (EI, 70 eV): m/z (%)¼301 ([M]þ,
29), 384 (12), 383 (10), 270 (17), 254 (15), 252 (100), 251 (21), 242
(41), 240 (12), 239 (31), 238 (54), 225 (13), 222 (63), 211 (11), 195
(10),194 (16),168 (12),166 (23),165 (62),153 (14),151 (11),139 (14),
128 (12), 115 (23), 82 (12), 77 (10). HRMS (EI): Calcd for C16H15O5N
([M]þ): 301.09447; found: 301.093882.
NMR (300 MHz, CDCl3):
d
¼0.88 (t, 3J¼7.2 Hz, 3H, (CH2)3CH3), 1.28–
1.40 (m, 2H, CH2), 1.52–1.62 (m, 2H, CH2), 2.64 (t, 3J¼7.2 Hz, 2H,
CH3(CH2)2CH2Ph), 3.31 (s, 3H, OCH3), 7.04–7.07 (m, 2H, CHPh), 7.23–
7.27 (m, 3H, CHPh), 7.68 (s, 1H, CHAr), 11.27 (s, 1H, OH). 13C NMR
(CDCl3, 75 MHz):
d
¼13.9 (CH3), 22.5, 29.4, 31.0 (CH2), 52.4 (OCH3),
112.9 (CCOOCH3), 127.6 (CHAr), 127.7 (2ꢂCHAr), 127.9 (2ꢂCHAr),
128.9 (CHAr), 132.1, 136.2, 136.6, 142.7 (CAr), 162.0 (COH), 170.8 (CO).
IR (neat, cmꢁ1):
¼3065 (w), 3006 (w), 2952 (w), 1674 (m), 1581
4.8.8. Methyl
20-chloro-3-hydroxy-6-nitrobiphenyl-2-carboxylate
~
n
(w), 1531 (w), 1438 (m), 1380 (w), 1356 (m), 1311 (s), 1232 (m), 1140
(m), 1090 (m), 1030 (w), 940 (w), 914 (m), 850 (w), 808 (m), 771
(m), 732 (m), 698 (s), 671 (m), 628 (m), 608 (m). GC–MS (EI, 70 eV):
m/z (%)¼329 ([M]þ, 48), 281 (12), 280 (59), 255 (18), 239 (15), 238
(100), 209 (10), 208 (36), 180 (10), 152 (21). HRMS (EI): Calcd for
C18H19O5N ([M]þ): 329.12577; found: 329.125828.
(13h). Starting with 12c (0.383 g, 1.5 mmol) and 5a (0.429 g,
1.7 mmol), 13h was isolated after chromatography (silica gel, hep-
tanes/EtOAc) as a yellowish solid (0.258 g, 56%), mp¼101–103 ꢀC.1H
NMR (300 MHz, CDCl3):
d
¼3.41 (s, 3H, OCH3), 6.92–7.02 (m, 1H,
CHAr), 7.09 (d, 3J¼9.0 Hz,1H, CHAr), 7.17–7.20 (m,1H, CHAr), 7.22–7.25
(m, 1H, CHAr), 7.35–7.38 (m, 1H, CHAr), 8.01 (d, 3J¼9.0 Hz, 1H, CHAr),
11.52 (s, 1H, OH). 13C NMR (CDCl3, 75 MHz):
d
¼52.8 (OCH3), 113.0
4.8.5. Methyl3-hydroxy-6-nitro-4-octylbiphenyl-2-carboxylate(13e). Star
ting with 12a (0.331 g, 1.5 mmol) and 5f (0.614 g, 1.7 mmol), 13e
was isolated after chromatography (silica gel, heptanes/EtOAc) as
(CCOOCH3),118.6,126.4,128.7,128.7,129.2,130.4 (CHAr),132.9,135.8,
136.5, 142.3 (CAr), 164.8 (COH), 169.9 (CO). IR (KBr, cmꢁ1):
n
¼3073
~
(w), 2952 (w),1673 (m),1599 (m),1578 (m),1519 (m),1480 (w),1440
(s),1323 (s),1230 (m),1204 (s),1127 (m),1049 (m), 968 (m), 914 (m),
841 (m), 811 (m), 750 (s), 737 (s), 698 (s), 644 (m), 592 (w). GC–MS
(EI, 70 eV): m/z (%)¼307 ([M]þ,10), 273 (15), 272 (100), 241 (10), 240
(66), 226 (12), 212 (18), 184 (15), 173 (10). HRMS (EI): Calcd for
C14H10O5NCl ([M]þ): 307.02420; found: 307.024320.
a yellowish oil (0.357 g, 62%). 1H NMR (300 MHz, CDCl3):
d
¼0.71 (t,
3J¼7.2 Hz, 3H, (CH2)7CH3), 1.08–1.15 (m, 10H, 5ꢂCH2), 1.43–1.55 (m,
2H, CH2), 2.56 (t, 3J¼7.0 Hz, 2H, CH3(CH2)6CH2Ph), 3.23 (s, 3H,
OCH3), 6.96–6.99 (m, 2H, CHPh), 7.17–7.19 (m, 3H, CHPh), 7.60 (s, 1H,
CHAr), 11.19 (s, 1H, OH). 13C NMR (CDCl3, 75 MHz):
d¼14.1 (CH3),
22.6, 28.8, 29.2, 29.3, 29.4, 29.6, 31.8 (CH2), 52.3 (OCH3), 112.9
(CCOOCH3), 127.6 (CHAr), 127.4 (2ꢂCHAr), 127.9 (2ꢂCHAr), 128.9
(CHAr), 132.1, 136.2, 136.6, 142.7 (CAr), 162.0 (COH), 170.8 (CO). IR
~
4.8.9. Methyl 20-chloro-3-hydroxy-4-methyl-6-nitrobiphenyl-2-carb-
oxylate (13i). Starting with 12c (0.383 g, 1.5 mmol) and 5b (0.457 g,
1.7 mmol), 13i was isolated after chromatography (silica gel, hep-
tanes/EtOAc) as a yellowish solid (0.337 g, 70%), mp¼100–102 ꢀC. 1H
(neat, cmꢁ1):
n
¼3060 (w), 2952 (w), 2923 (m), 1666 (m), 1570 (w),
1526 (m), 1437 (m), 1336 (s), 1250 (m), 1164 (m), 1126 (m), 1074 (w),
1029 (w), 964 (w), 914 (w), 843 (w), 814 (m), 754 (m), 733 (m), 697
NMR (300 MHz, CDCl3):
d
¼2.31 (s, 3H, CH3), 3.40 (s, 3H, OCH3), 6.99

A. Riahi et al. / Tetrahedron 65 (2009) 9300–9315
9313
(dd, 3J¼6.9 Hz, 4J¼1.8 Hz,1H, CHAr), 7.15–7.26 (m, 2H, CHAr), 7.35 (dd,
129.1 (2ꢂCHAr), 132.7, 136.0, 139.7 (CAr), 153.0 (COH), 171.4 (CO). IR
3J¼7.7 Hz, 4J¼1.5 Hz,1H, CHAr), 7.90 (s,1H, CHAr),11.79 (s,1H, OH).13
C
(neat, cmꢁ1):
~
n
¼3447 (w), 3056 (w), 2964 (w), 2872 (w), 1654 (m),
NMR (CDCl3, 75 MHz):
d
¼16.0 (CH3), 52.8 (OCH3), 112.0 (CCOOCH3),
1611 (m), 1585 (m), 1496 (w), 1429 (m), 1371 (m), 1326 (m), 1264
(m), 1205 (s), 1149 (m), 1106 (m), 1065 (m), 1014 (m), 968 (w), 909
(m), 853 (m), 803 (m), 762 (m), 731 (m), 699 (s), 681 (m), 645 (m),
569 (m). GC–MS (EI, 70 eV): m/z (%)¼285 ([M]þ, 30), 240 (17), 239
(100), 221 (11), 211 (13), 196 (25), 167 (11). HRMS (EI): Calcd for
C17H19O3N ([M]þ): 285.13594; found: 285.135726.
126.4 (CHAr),128.5 (CAr),128.6,128.8,129.0,130.5 (CHAr),133.0,133.8,
136.2, 141.6 (CAr),163.4 (COH),170.5 (CO). IR (KBr, cmꢁ1):
n
¼2955 (w),
~
2853 (w), 1731 (w), 1664 (s), 1574 (m), 1521 (m), 1429 (m), 1378 (m),
1341 (s), 1265 (s), 1200 (s), 1128 (m), 1057 (m), 98 (m), 946 (w), 899
(m), 859 (w), 810 (m), 754 (m), 739 (s), 698 (s), 657 (m), 630 (m), 534
(w). GC–MS (EI, 70 eV): m/z (%)¼321 ([M]þ, 10), 287 (17), 286 (100),
255 (12), 254 (77), 226 (12), 198 (17), 152 (24), 139 (10). HRMS (EI):
Calcd for C15H12O5NCl ([M]þ): 321.03985; found: 321.039927.
4.9.4. Methyl 6-amino-4-butyl-3-hydroxybiphenyl-2-carboxylate
(14d). Starting with 13d (0.130 g, 0.394 mmol), 14d was isolated
(0.108 g, 92%) by column chromatography (silica gel, heptanes/
EtOAc¼30:1/20:1) as a yellowish oil. 1H NMR (300 MHz, CDCl3):
4.9. General procedure for the synthesis of 4-aminophenols
(14a–i)
d
¼0.82 (t, 3J¼6.7 Hz, 3H, (CH2)3CH3), 1.15–1.18 (m, 2H, CH2), 1.50–
1.59 (m, 2H, CH2), 2.56 (t, 3J¼7.6 Hz, 2H, CH3(CH2)2CH2Ph), 3.06 (br,
2H, NH2), 3.29 (s, 3H, OCH3), 6.75 (s, 1H, CHAr), 7.07–7.12 (m, 2H,
CHAr), 7.21–7.25 (m,1H, CHAr), 7.32–7.36 (m, 2H, CHAr),10.35 (br,1H,
To a methanol suspension (25 mL/1 mmol of 13a–i) of 13a–i
(1.0 equiv)oranethanol suspensionof 13c (1.0 equiv)wasadded Pd/C
(10 mol %, 0.1 equiv). The mixture was set under a hydrogen atmo-
sphere. After stirring for 48 h at 20 ꢀC, the reaction mixture was fil-
tered (Celite) and the filtrate was concentrated in vacuo. The residue
was purified by chromatography (silica gel, heptanes/EtOAc¼2:1).
OH). 13C NMR (CDCl3, 75 MHz):
d¼13.9 (CH3), 22.5, 29.4, 31.0 (CH2),
51.4 (OCH3),112.0 (CCOOCH3),123.5 (CHAr),125.0 (CAr),126.7 (CHAr),
128.5 (2ꢂCHAr),129.1 (2ꢂCHAr),131.4,136.0,139.5 (CAr),152.8 (COH),
171.3 (CO). IR (neat, cmꢁ1):
n
¼3454 (w), 3055 (w), 2922 (m), 2851
~
(w),1660 (m),1598 (m),1493 (w),1433 (m),1315 (m),1263 (m),1207
(s), 1152 (m), 1108 (m), 1071 (w), 998 (w), 920 (w), 871 (w), 809 (w),
764 (m), 721 (m), 700 (s), 683 (m), 647 (m), 569 (m). HRMS(EI): Calcd
for C18H21O3N ([M]þ): 299.15299; found: 299.152209.
4.9.1. Methyl 6-amino-3-hydroxybiphenyl-2-carboxylate (14a). Star-
ting with 13a (0.130 g, 0.475 mmol), 14a was isolated (0.099 g, 86%)
by column chromatography (silica gel, heptanes/EtOAc¼30:1/
20:1) as a yellowish solid, mp¼95–97 ꢀC. 1H NMR (300 MHz, CDCl3):
d
¼3.02 (br, 2H, NH2), 3.30 (s, 3H, OCH3), 6.82–6.84 (m, 2H, CHAr),
4.9.5. Methyl
6-amino-3-hydroxy-4-octylbiphenyl-2-carboxylate
7.08–7.11(m,2H,CHPh), 7.22–7.35(m,3H,CHPh),10.07(br,1H,OH).13
NMR (CDCl3, 75 MHz):
C
(14e). Starting with 13e (0.150 g, 0.389 mmol), 14e was isolated
(0.124 g, 90%) by column chromatography (silica gel, heptanes/
EtOAc¼30:1/20:1) as a yellowish oil. 1H NMR (300 MHz, CDCl3):
d¼51.6 (OCH3), 112.5 (CCOOCH3), 117.7, 123.1,
127.0, (CHAr),127.5 (CAr),128.5 (2ꢂCHAr),128.9 (2ꢂCHAr),136.9,139.1
(CAr), 154.7 (COH), 171.3 (CO). IR (KBr, cmꢁ1):
n
¼3742 (w), 3060 (w),
d
¼0.81 (t, 3J¼6.5 Hz, 3H, (CH2)7CH3), 1.17–1.25 (m, 10H, 5ꢂCH2),
~
2922 (w), 2788 (w), 2671 (w), 1721 (s), 1586 (m),1488 (m),1455 (m),
1433 (m), 1348 (m), 1302 (m), 1277 (s), 1239 (m), 1217 (s), 1158 (m),
1110 (m),1087 (m),1029 (w), 982 (m), 949 (m), 911 (m), 871 (m), 807
(m), 776 (m), 750 (m), 730 (m), 719 (s), 698 (s), 646 (m), 613 (m), 549
(m). GC–MS (EI, 70 eV): m/z (%)¼243 ([M]þ, 32), 212 (16), 211 (100),
183 (24), 155 (15), 154 (67), 128 (16), 127 (10), 77 (10). HRMS (EI):
Calcd for C14H13O3N ([M]þ): 243.08899; found: 243.089209.
1.51–1.61 (m, 2H, CH2), 2.56 (t, 3J¼7.8 Hz, 2H, CH3(CH2)6CH2Ph), 3.08
(br, 2H, NH2), 3.28 (s, 3H, OCH3), 6.74 (s, 1H, CHAr), 7.07–7.11 (m, 2H,
CHAr), 7.20–7.25 (m,1H, CHAr), 7.30–7.35 (m, 2H, CHAr),10.34 (br,1H,
OH). 13C NMR (CDCl3, 75 MHz):
d¼14.1 (CH3), 22.6, 29.3, 29.5, 29.5,
29.6, 30.3, 31.9 (CH2), 51.5 (OCH3), 111.9 (CCOOCH3), 123.4 (CHAr),
125.1 (CAr), 126.8 (CHAr), 128.4 (2ꢂCHAr), 129.0 (2ꢂCHAr), 131.5,
135.9, 139.4 (CAr), 152.9 (COH), 171.7 (CO). IR (neat, cmꢁ1):
~
n
¼3455
(w), 3056 (w), 2922(m), 2852 (w),1659 (m),1599 (m),1497 (w),1434
(m), 1317 (m), 1263 (m), 1208 (s), 1150 (m), 1108 (m), 1071 (w), 997
(w), 919 (w), 881 (w), 804 (w), 764 (m), 721 (m), 700 (s). GC–MS (EI,
70 eV): m/z (%)¼355 ([M]þ, 65), 324 (27), 323 (100), 322 (11), 306
(12), 266 (25), 252 (18), 324 (27), 323 (100), 322 (11), 306 (12), 266
(25), 252 (18), 238 (27), 225 (41), 224 (47), 209 (10), 208 (10), 197
(10), 196 (30), 180 (11), 168 (23), 167 (21), 41 (10). HRMS (EI): Calcd
for C22H29O3N ([M]þ): 355.21420; found: 355.214070.
4.9.2. Methyl 6-amino-3-hydroxy-4-methylbiphenyl-2-carboxylate
(14b). Starting with 13b (0.140 g, 0.487 mmol), 14b was isolated
(0.107 g, 85%) by column chromatography (silica gel, heptanes/
EtOAc¼30:1/20:1) as a yellowish oil. 1H NMR (300 MHz, CDCl3):
d
¼2.17 (s, 3H, CH3), 3.09 (br, 2H, NH2), 3.28 (s, 3H, OCH3), 6.73 (s, 1H,
CHAr), 7.06–7.09 (m, 2H, CHAr), 7.22–7.25 (m,1H, CHAr), 7.29–7.34 (m,
2H, CHAr),10.36 (br,1H, OH).13C NMR (CDCl3, 75 MHz):
51.5 (OCH3), 111.7 (CCOOCH3), 124.2 (CHAr), 125.0 (CAr), 126.8 (CHAr),
d
¼16.3 (CH3),
128.4 (2ꢂCHAr),129.3 (2ꢂCHAr),132.5,136.0,139.4 (CAr),153.1 (COH),
4.9.6. Methyl 6-amino-3-hydroxy-20-methylbiphenyl-2-carboxylate
(14f). Starting with 13f (0.120 g, 0.417 mmol), 14f was isolated
(0.097 g, 91%) by column chromatography (silica gel, heptanes/
EtOAc¼30:1/20:1) as a yellowish viscous oil. 1H NMR (300 MHz,
171.7 (CO). IR(neat, cmꢁ1):
~
n
¼3444 (w), 3057 (w), 2924(w), 2851 (w),
1726 (w),1658 (m),1587 (m),1499 (w),1434 (m),1347 (m),1306 (m),
1280 (m), 1208 (s), 1149 (m), 1106 (m), 1072 (m), 1023 (m), 983 (m),
907 (m), 863 (m), 802 (m), 764 (m), 730 (s), 700 (s), 689 (s), 645 (m),
565 (m). GC–MS (EI, 70 eV): m/z (%)¼257 ([M]þ, 33), 226 (17), 225
(100), 197 (24), 169 (11), 168 (53), 167 (14), 154 (12), 128 (9). HRMS
(EI): Calcd for C15H15O3N ([M]þ): 257.10464; found: 257.104582.
CDCl3):
d
¼1.98 (s, 3H, CH3), 3.02 (br, 2H, NH2), 3.31 (s, 3H, OCH3), 6.68
(d, 3J¼8.0 Hz, 1H, CHAr), 6.92–6.94 (m, 1H, CHAr), 7.18–7.23 (m, 3H,
CHAr), 8.0 (d, 3J¼8.2 Hz, 1H, CHAr), 9.98 (br, 1H, OH). 13C NMR (CDCl3,
75 MHz):
d
¼19.5 (CH3), 51.7 (OCH3), 112.1 (CCOOCH3), 117.6, 123.8,
126.1, 127.4 (CHAr), 127.8 (CAr), 128.9, 129.9 (CHAr), 135.3, 136.2, 138.1
(CAr), 153.5 (COH), 171.7 (CO). IR (neat, cmꢁ1):
n
¼3451 (w), 3060 (w),
~
4.9.3. Ethyl
6-amino-4-ethyl-3-hydroxybiphenyl-2-carboxylate
(14c). Starting with 13c (0.130 g, 0.418 mmol), 14c was isolated
(0.111 g, 95%) by column chromatography (silica gel, heptanes/
EtOAc¼30:1/20:1) as a yellowish oil. 1H NMR (300 MHz, CDCl3):
2921 (w), 2851 (w),1664 (m),1598 (m),1489 (w),1463 (m),1436 (m),
1411 (w), 1335 (m), 1312 (m), 1287 (m), 1212 (s), 1119 (m), 1087 (m),
1037 (m), 982 (w), 913 (m), 806 (m), 757 (m), 734 (s), 689 (m), 624
(m), 565 (m). GC–MS (EI, 70 eV): m/z (%)¼257 ([M]þ, 39), 226 (17),
225 (100), 169 (15), 168 (50), 167 (10), 154 (10), 115 (9). HRMS (EI):
Calcd for C15H15O3N ([M]þ): 257.10464; found: 257.104502.
d
¼0.58 (t, 3J¼7.0 Hz, 3H, CH2CH3),
d
¼1.17 (t, 3J¼7.6 Hz, 3H,
OCH2CH3), 2.60 (q, 3J¼7.6 Hz, 2H, CH2CH3), 3.09 (br, 2H, NH2), 3.81
(q, 3J¼7.0 Hz, 2H, OCH2CH3), 6.76 (s, 1H, CHAr), 7.08–7.11 (m, 2H,
CHAr), 7.21–7.34 (m, 3H, CHAr), 10.58 (br, 1H, OH). 13C NMR (CDCl3,
75 MHz):
d
¼12.8, 13.7 (CH3), 23.0 (CH2), 60.6 (OCH2), 111.8
4.9.7. Methyl 6-amino-3-hydroxy-20,4-dimethylbiphenyl-2-carboxy-
late (14g). Starting with 13g (0.140 g, 0.464 mmol), 14g was
(CCOOCH3), 122.5 (CHAr), 125.1 (CAr), 126.7 (CHAr), 128.4 (2ꢂCHAr),

9314
A. Riahi et al. / Tetrahedron 65 (2009) 9300–9315
3. (a) Nadin, L.; Murray, M. Biochem. Pharmacol. 1999, 58, 1201; (b) Fent, K.; Escher,
C.; Caminada, D. Reprod. Toxicol. 2006, 22, 175; (c) Khamdang, S.; Takeda, M.;
Noshiro, R.; Narikawa, S.; Enomoto, A.; Anzai, N.; Piyachaturawat, P.; Endou, H.
J. Pharmacol. Exp. Ther. 2002, 303, 534; (d) Gobec, S.; Brozic, P.; Rizner, T. L.
Bioorg. Med. Chem. Lett. 2005, 15, 5170; (e) Tran, T.; Saheba, E.; Arcerio, A. V.;
Chavez, V.; Li, Q.-y.; Martinez, L. E.; Primm, T. P. Bioorg. Med. Chem. 2004, 12,
4809.
4. (a) Alvi, K. A.; Nair, B.; Gallo, C.; Baker, D. J. Antibiot. 1997, 50, 264; (b) de
Oliveira, M. F.; Oliveira, J. H. H. L.; Galetti, F. C. S.; de Souza, A. O.; Silva, C. L.;
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isolated (0.112 g, 89%) by column chromatography (silica gel, hep-
tanes/EtOAc¼30:1/20:1) as a yellowish oil. 1H NMR (300 MHz,
CDCl3):
d
¼1.98 (s, 3H, CH3), 2.19 (s, 3H, CH3), 3.04 (br, 2H, NH2), 3.30
(s, 3H, OCH3), 6.77 (s, 1H, CHAr), 6.88–6.91 (m, 1H, CHAr), 7.12–7.18
(m, 3H, CHAr), 10.61 (br, 1H, OH). 13C NMR (CDCl3, 75 MHz):
d
¼16.0,
19.5 (CH3), 51.6 (OCH3), 111.3 (CCOOCH3), 124.3 (CHAr), 124.5 (CAr),
126.0 (CHAr), 126.6 (CAr), 127.2, 128.8, 129.7 (CHAr), 135.5, 136.4,
138.6 (CAr), 153.5 (COH), 171.7 (CO). IR (neat, cmꢁ1):
n
¼3447 (w),
~
3057 (w), 2920 (w), 2850 (w), 1726 (w), 1658 (m), 1610 (m), 1456
(m), 1434 (s), 1377 (m), 1342 (m), 1284 (m), 1208 (s), 1150 (m), 1101
(m), 1023 (m), 983 (m), 909 (w), 869 (m), 804 (m), 758 (s), 728 (s),
678 (m), 645 (m), 578 (m). GC–MS (EI, 70 eV): m/z (%)¼271 ([M]þ,
39), 240 (17), 239 (100), 183 (10), 182 (25), 168 (30), 167 (13). HRMS
(EI): Calcd for C16H17O3N ([M]þ): 271.12029; found: 271.120370.
6. Ismail, L. D.; Lorenz, P.; Stermitz, F. J. Nat. Prod. 1998, 61, 1174.
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Ngando, T. M.; Fomum, Z. T. Chem. Pharm. Bull. 2006, 54, 1034; (c) Tsai, I.-L.;
Wun, M.-F.; Teng, C.-M.; Ishikawa, T.; Chen, I.-S. Phytochemistry 1998, 48, 1377;
(d) Tsai, I.-L.; Fang, S.-C.; Ishikawa, T.; Chang, C.-T.; Chen, I.-S. Phytochemistry
1997, 44, 1383.
4.9.8. Methyl 6-amino-20-chloro-3-hydroxybiphenyl-2-carboxylate
(14h). Starting with 13h (0.120 g, 0.390 mmol), 14h was isolated
(0.095 g, 88%) by column chromatography (silica gel, heptanes/
EtOAc¼30:1/20:1) as a brown oil. 1H NMR (300 MHz, CDCl3):
d
¼3.03 (br, 2H, NH2), 3.30 (s, 3H, OCH3), 6.85 (d, 3J¼8.0 Hz, 1H,
CHAr), 7.09–7.11 (m, 2H, CHAr), 7.23–7.28 (m, 2H, CHAr), 7.32–7.37
(m, 2H, CHAr), 10.29 (br, 1H, OH). 13C NMR (CDCl3, 75 MHz):
(OCH3), 112.4 (CCOOCH3), 117.7, 123.3, 127.0 (CHAr), 127.8 (CAr),
d
¼51.6
128.5, 128.5, 128.8 (CHAr), 135.5, 136.4, 139.0 (CAr), 154.8 (COH),
171.2 (CO). IR (neat, cmꢁ1):
n
¼3445 (w), 3056 (w), 2950 (w), 2850
~
(w), 1728 (w), 1663 (m), 1594 (m), 1463 (m), 1435 (s), 1335 (m), 1285
(m), 1209 (s), 1092 (m), 1027 (m), 982 (m), 805 (m), 759 (m), 732
(m), 700 (s), 626 (m), 580 (m). GC–MS (EI, 70 eV): m/z (%)¼277
([M]þ, 42), 246 (14), 245 (100), 211 (19), 210 (59), 183 (10), 182 (52),
154 (62), 153 (13), 127 (14), 77 (11). HRMS (EI): Calcd for
C14H12O3NCl ([M]þ): 277.05002; found: 277.050203.
4.9.9. Methyl 6-amino-20-chloro-3-hydroxy-4-methylbiphenyl-2-carb-
oxylate (14i). Starting with 13i (0.120 g, 0.373 mmol), 14i was
isolated (0.097 g, 90%) by column chromatography (silica gel,
heptanes/EtOAc¼30:1/20:1) as a brown oil. 1H NMR (300 MHz,
CDCl3):
d
¼2.19 (s, 3H, CH3), 3.02 (br, 2H, NH2), 3.29 (s, 3H, OCH3),
6.78 (s, 1H, CHAr), 7.07–7.10 (m, 1H, CHAr), 7.23–7.26 (m, 1H, CHAr),
7.30–7.35 (m, 2H, CHAr), 10.42 (br, 1H, OH). 13C NMR (CDCl3,
75 MHz):
d
¼16.0 (CH3), 51.5 (OCH3), 111.7 (CCOOCH3), 124.3 (CHAr),
125.3 (CAr), 126.8 (CHAr), 127.8 (CAr), 128.4 (2ꢂCHAr), 129.0 (CHAr),
12. Llabres, J. M.; Viladomat, F.; Bastida, J.; Codina, C.; Rubiralta, M. Phytochemistry
1986, 25, 2637. For synthetic work, see; (a) Ganton, M. D.; Kerr, M. A. Org. Lett.
2005, 7, 4777; (b) Torres, J. C.; Pinto, A. C.; Garden, S. J. Tetrahedron 2004, 60,
9889.
132.5, 135.5, 139.2 (CAr), 153.4 (COH), 171.6 (CO). IR (neat, cmꢁ1):
~
n
¼3447 (w), 3056 (w), 2949 (w), 2851 (w), 1731 (w), 1658 (m), 1612
(m), 1599 (m), 1498 (w), 1434 (s), 1377 (m), 1280 (m), 1206 (s), 1149
(m), 1105 (m), 1072 (m), 1005 (m), 983 (m), 919 (w), 803 (m), 763
(m), 700 (s), 644 (m), 588 (m). GC–MS (EI, 70 eV): m/z (%)¼257
([M]þ, 33), 226 (17), 225 (100), 197 (22), 168 (49), 167 (14), 154 (11).
HRMS (EI): Calcd for C15H14O3NCl ([M]þ): 291.07029; found:
291.070370.
13. (a) Kleppinger, R.; Lillya, C. P.; Yang, C. J. Am. Chem. Soc. 1997, 119, 4097;
(b) Mohanakrishnan, A. K.; Srinivasan, P. C. J. Org. Chem. 1995, 60, 1939.
14. Delaude, L.; Laszlo, P.; Smith, K. Acc. Chem. Res. 1993, 26, 607.
15. Ramana, M. M. V.; Malik, S. S.; Parihar, J. A. Tetrahedron Lett. 2004, 45, 8681.
16. Rajagopal, R.; Srinivasan, K. V. Synth. Commun. 2003, 33, 961.
17. (a) Poesche, W. H. J. Chem. Soc. C 1966, 890; (b) Forrest, J. J. Chem. Soc. 1960, 589;
(c) Helmchen, G.; Prelog, V. Helv. Chim. Acta 1972, 55, 2599; (d) Suzuki, H.; Enya,
T.; Hisamatsu, Y. Synthesis 1997, 1273; (e) Bell, A. J.; Read, R. W. Aust. J. Chem.
1987, 40, 1813; (f) Take, K.; Okumura, K.; Takimoto, K.; Kato, M.; Ohtsuka, M.;
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Acknowledgements
18. Metal-Catalyzed Cross-Coupling Reactions; de Meijere, A., Diederich, F., Eds.;
Wiley-VCH: Weinheim, 2004.
19. (a) Elango, S.; Srinivasan, P. C. Tetrahedron Lett. 1993, 34, 1347; (b) Dow, R. L.;
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Financial support by the State of Pakistan (HEC scholarships for
M.A.Y. and I.H.) and by the State of Mecklenburg-Vorpommern
(scholarship for M.S.) is gratefully acknowledged.
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