A facile method for synthesis of polysubstituted naphthalene derivatives through pyrrolidine catalyzed domino reaction

Article abstract of DOI:10.1016/j.tet.2010.08.069

A novel synthetic method for polysubstituted naphthalene derivatives via a pyrrolidine-mediated cascade Michael/Henry reaction was developed, in which easily prepared 2-(2-oxoethyl)benzaldehydes and nitroalkenes were employed as the starting materials. The reaction consists of four consecutive reactions that include a cascade Michael/Henry reaction, a dehydration reaction, and an aromatization reaction in one pot to afford synthetically important naphthalene derivatives with moderate yields.

Full text of DOI:10.1016/j.tet.2010.08.069

Tetrahedron 66 (2010) 8557e8561
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
A facile method for synthesis of polysubstituted naphthalene derivatives through
pyrrolidine catalyzed domino reaction
*
Shi-Guang Li, Xiu-Qin Hu, Zhen-Xin Jia, Peng-Fei Xu
State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 1 June 2010
Received in revised form 30 August 2010
Accepted 31 August 2010
A novel synthetic method for polysubstituted naphthalene derivatives via a pyrrolidine-mediated cas-
cade Michael/Henry reaction was developed, in which easily prepared 2-(2-oxoethyl)benzaldehydes and
nitroalkenes were employed as the starting materials. The reaction consists of four consecutive reactions
that include a cascade Michael/Henry reaction, a dehydration reaction, and an aromatization reaction in
one pot to afford synthetically important naphthalene derivatives with moderate yields.
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Organocatalysis
Naphthalenes
Nitroalkenes
Michael/Henry reaction
1. Introduction
2. Results and discussion
Substituted naphthalene derivatives have emerged as very im-
portant biological entities1 and frequently are employed as starting
materials for the preparation of more complex polynuclear aromatic
ring systems.2 The development of new and efficient methodologies
for the synthesis of polysubstituted naphthalene derivatives has
recently attracted much attention. A variety of methods, such as
transition-metal-catalyzed [2þ2þ2] alkyne cyclizations;3 Lewis acid
catalyzed cyclization of carbonyl compounds with alkynes;4 and
[4þ2] cyclizations,5 have been reported for their construction.6
However, the overall process sometimes suffers relatively expen-
sive catalysts, harsh reaction conditions, multi-step synthesis, and
a mixture of isomers. To the best of our knowledge, using small
organic molecules as catalysts to synthesize polysubstituted naph-
thalene derivatives has not been reported. In the past decade
organocatalysis has been referred to as a research topic with many
advantages in synthetic organic chemistry, and the field of orga-
nocatalysis has now reached adolescence7 making many once
unthinkable syntheses possible. Compared to other types of organic
synthesis reaction, organocatalysts have incomparable advantages.
As a further application of the organocatalyst in organic synthesis
reactions, we have developed a tandem Michael/Henry reaction
between 2-(2-oxoethyl)benzaldehydes and nitroalkenes to afford
polysubstituted naphthalene derivatives in a single operation.
Recently, Hayashi, etc.8aec successfully used aqueous pentane-
1,5-dial and nitroalkene in a highly enantioselective domino syn-
thesis of optically active cyclohexane derivatives. Our group has
developed an enantioselective synthetic method for substituted
tetrahydropyridines via a proline-mediated cascade Mannich-
type/intramolecular cyclization of N-PMP aldimines.8d We antici-
pated that 2-(2-oxoethyl)benzaldehyde, an analogue of pentane-
1,5-dial, might be utilized for the formation of optically active
tetrahydronaphthalenes by a cascade Michael/Henry cyclization
reaction catalyzed by organic molecules. Then, the reaction be-
tween 2-(2-oxoethyl)benzaldehyde 1a and (2-nitrovinyl)benzene
2a, using L-proline(0.2 equiv) as a catalyst and DMAP(0.2 equiv) as
an additive, was investigated in methylene chloride in the pres-
ence of water. After the completion of the reaction the dehydration
and aromatization product 3-nitro-2-phenyl-1-naphthaldehyde
3a (isolated in 44% yield) was obtained instead of the expected
product (Table 1, entry 1). Based on this result, efforts were made
to improve the yield of this novel synthetic reaction for synthesis
of polysubstituted naphthalene derivatives (Table 1).
First, we performed a catalyst screening with various amines
and found that pyrrolidine could catalyze the reaction efficiently to
furnish the desired product 3a in 58% yield, and glycine could not
catalyze the reaction (Table 1, entries 2 and 3). Next we examined
different solvents with pyrrolidine as the catalyst and found that
methylene chloride was the optimal one for this cascade process,
and both tetrahydrofuran and methanol gave lower yields of the
desired product (Table 1, entries 4 and 5). To test the effect of the
* Corresponding author. Tel.: þ86 931 891 2281; fax: þ86 931 891 5557; e-mail
address: xupf@lzu.edu.cn (P.-F. Xu).
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.08.069

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S.-G. Li et al. / Tetrahedron 66 (2010) 8557e8561
Table 1
nitroethenes (Table 2, entries 2e9), while it is slow with electron-
Optimization of the reaction conditionsa
rich aryl-substituted ones (Table 2, entries 10e11). The hetero-
aromatic group, such as furyl, could also successfully afford the
desired product in moderate yield (Table 2, entry 12). Furthermore,
dialdehydes with 5-Br, 4-Br or 5-CH3 group could act as four-carbon
units in this reaction (Table 2, entries 13e18), and the corre-
sponding cascade reaction was a little slower. And we have in-
vestigated the reaction of 3-methyl-2-(2-oxoethy l)benzaldehyde
1e with nitroalkene in general Experimental procedure (Table 2,
entry 19). However, after the completion of the reaction the
dehydration product dihydronaphthalene 8s (isolated in 53% yield)
was obtained instead of the expected product 8-methyl-3-nitro-2-
phenyl-1-naphthaldehyde 3s, suggesting that the spatial effect of
3-CH3 group prevented oxidative dehydrogenation process. A
nitroalkene with an alkyl group, such as n-propyl did not give the
corresponding naphthalene, perhaps because of the lability of the
aliphatic nitroalkene in the presence of water (Table 2, entry 20).
Based on previous experience8a with Michael/Henry reactions,
the following stepwise cascade reaction mechanism was proposed
to account for the outcome of the reaction (Scheme 1). The dia-
ldehyde would react with pyrrolidine to form the enamine 4, which
undergoes Michael reaction with a nitroalkene to generate 5.
Zwitterion 5 would then react with the aldehyde moiety via an
intramolecular Henry reaction to provide 6, which is hydrolyzed to
give the key intermediate tetrahydronaphthalene 7. Under aqueous
basic conditions, the unstable intermediate 7 undergoes de-
hydration to afford dihydronaphthalene 8, which is further oxi-
dized by air9 to furnish the final polysubstituted naphthalene 3.
NO2
CHO
conditions
0oC-rt
NO2
+
CHO
CHO
2a
1a
3a
entry
Catalyst
Solventb
Additive
t/h
48
48
72
72
72
72
72
72
72
Yieldc
%
1
2
3
4
5
6
7
8
9
10
Proline
Pyrrolidine
Glycine
Pyrrolidine
Pyrrolidine
Pyrrolidine
Pyrrolidine
Pyrrolidine
Pyrrolidine
Pyrrolidine
CH2Cl2
CH2Cl2
CH2Cl2
THF
MeOH
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
DMAP
DMAP
DMAP
DMAP
DMAP
DABCO
K2CO3
TEA
44
58
0
40
23
41
28
19
37
8
DIPEA
d
144
a
Unless otherwise specified, all reactions were carried out with 1a (0.4 mmol), 2a
(0.2 mmol), organocatalyst (20 mol %), and additive (20 mol %) in the indicated
solvent and water (2.0 mL, Vsolvent/Vwater¼1:1) at 0 ꢀC for 4 h, and then the reaction
mixture was stirred vigorously at room temperature.
b
Vsolvent/Vwater¼1:1.
c
Isolated yield of the product 3a after flash chromatography.
additive on the yield, we employed various bases (Table 1, entries
6e9) and found that all the additives promoted the reaction to
afford the desired product 3a in lower yields compared to DMAP.
Reaction without an additive resulted in much longer reaction time
and much lower yield (Table 1, entry 10). Thus, we preferred to
perform this cascade reaction with DMAP as the additive.
Under the optimized reaction conditions, the generality of the
reaction was investigated by employing several substituted dia-
ldehydes and nitroalkenes. The results are summarized in Table 2.
The reaction is fast with electron-deficient aryl-substituted
Table 2
The synthesis of polysubstituted naphthalene derivativesa
NO2
R2
pyrrolidine
DMAP
CHO
CHO
R1
NO2
R1
+
R2
CH2Cl2:H2O=1:1
0oC-rt
CHO
2
3
1
entry
R1
R2
t/h
Product
Yieldb
%
1
2
3
4
5
6
7
8
H
H
H
H
H
H
H
H
H
H
H
H
5-CH3
5-CH3
5-Br
5-Br
5-Br
4-Br
3-CH3
H
Ph
48
48
48
48
48
48
48
48
48
72
72
72
72
72
72
72
72
72
72
72
3a
3b
3c
3d
3e
3f
3g
3h
3i
58
59
62
62
61
58
46
45
62
51
52
50
55
65
63
63
65
64
53
0
2-BreC6H4
3-BreC6H4
4-BreC6H4
3-CleC6H4
4-CleC6H4
3-NO2eC6H4
4-NO2eC6H4
4-CNeC6H4
4-CH3eC6H4
2-OCH3eC6H4
2-Furyl
Ph
3-BreC6H4
Ph
Scheme 1. Proposed mechanism for the cascade reaction.
As illustrated in Scheme 2, the polysubstituted naphthalene
derivates 3 could be smoothly converted to some versatile building
blocks for organic syntheses. The compound 3a was converted into
(3-amino-2-phenylnaphthalen-1-yl)methanol 9 by reduction with
NaBH4 and subsequent deoxidation under the catalysis of Fe/HCl.
Furthermore, we converted 9 into (3-azido-2-phenylnaphthalen-1-
yl)methanol 10, which was used to react with NaN3 in the presence
of NaNO2 and HCl.11 These successful reactions provide evidence
that the current domino reaction is a useful methodology in the
synthesis of polysubstituted naphthalene derivatives.
9
10
11
12
13
14
15
16
17
18
19c
20
3j
3k
3l
3m
3n
3o
3p
3q
3r
3s
d
3-BreC6H4
4-BreC6H4
Ph
Ph
n-Pr
a
Unless otherwise specified, all reactions were carried out with 1 (0.4 mmol), 2
(0.2 mmol), pyrrolidine (20 mol %), and DMAP (20 mol %) in CH2Cl2 and water
(2.0 mL, VDCM/Vwater¼1:1) at 0 ꢀC for 4 h, and then the reaction mixture was stirred
vigorously at room temperature.
b
Isolated yield of the product 3 after flash chromatography.
Isolated product was not 3s, but dihydronaphthalene 8s.
c
Scheme 2. Synthesis of compounds 9 and 10.

S.-G. Li et al. / Tetrahedron 66 (2010) 8557e8561
8559
3. Conclusion
1531, 1344, 1218, 762 cmꢁ1; MS (EI, 70 eV), m/z (%): 276 (100), 230
(51), 200 (32), 189 (15), 100(9).
In summary, we have developed a novel synthetic method for
polysubstituted naphthalene derivatives via a pyrrolidine-mediated
cascade cyclization reaction, inwhich easily prepared 2-(2-oxoethyl)
benzaldehydes and nitroalkenes are employed as the starting ma-
terials. The reaction consists of four consecutive reactions that in-
clude a cascade Michael/Henry reaction, a dehydration reaction, and
an aromatization reaction in one pot to afford synthetically impor-
tant naphthalene derivatives in moderate yields. Based on the im-
portant results, the synthetic applications of this cascade reaction
are currently under active investigations.
4.2.3. 2-(3-Bromophenyl)-3-nitronaphthalene-1-carbaldehyde
(3c). Light yellow solid, mp 153e154 ꢀC; 1H NMR (CDCl3, 400 MHz)
d
10.00 (s, 1H), 9.12 (d, J¼8.4 Hz, 1H), 8.61 (s, 1H), 8.06 (d, J¼8.4 Hz,
1H), 7.88e7.84 (m, 1H), 7.75 (t, J¼7.6 Hz, 1H), 7.64 (dd, J¼1.2, 8.0 Hz,
1H), 7.54 (s, 1H), 7.37 (t, J¼8.0 Hz, 1H), 7.31 (d, J¼7.6 Hz, 1H); 13C
NMR (CDCl3, 100 MHz) d 192.6, 147.1, 137.1, 134.8, 132.5, 132.3, 132.2,
132.0, 131.8, 131.2, 130.0, 129.6, 129.2, 128.9, 128.5, 126.1, 122.8; IR
(KBr): 3399, 2922, 2853, 1687, 1528, 1341, 757 cmꢁ1; MS (EI, 70 eV),
m/z (%): 355 (Mþ, 21), 338 (62), 308 (59), 259 (40), 229 (27), 200
(100), 189 (38), 100 (67).
4. Experimental section
4.1. General
4.2.4. 2-(4-Bromophenyl)-3-nitro-1-naphthaldehyde (3d). Light yel-
low solid, mp 114e115 ꢀC; 1H NMR (CDCl3, 400 MHz)
d 9.99 (s, 1H),
9.10 (d, J¼8.4 Hz, 1H), 8.58 (s, 1H), 8.05 (d, J¼8.4 Hz, 1H), 7.87e7.83
All reactions were performed under an air atmosphere unless
otherwise stated. All glass apparatuses were dried and cooled be-
fore use. Reagents used were obtained from commercial suppliers
or redistilled. In all cases of chromatography, distilled solvents were
used as eluents. Flash chromatography was performed on silica gel
(200e300 mesh). Thin-layer chromatography (TLC) was carried out
using GF254 (200e300 mesh) fluorescent treated silica, which was
visualised under UV light (250 nm) or by staining with phospho-
molybdic acid solutions as a chromogenic reagent.
(m,1H), 7.74 (t, J¼7.6 Hz,1H), 7.63 (d, J¼8.4 Hz, 2H), 7.24 (d, J¼8.4 Hz,
2H); 13C NMR (CDCl3, 100 MHz)
d 192.6, 147.2, 137.4, 132.2, 131.9,
131.8, 131.8, 131.7, 131.4, 131.2, 129.6, 129.0, 128.9, 126.0, 123.7; IR
(KBr): 3364, 3072, 2922, 1690, 1530, 1340, 1068, 761 cmꢁ1; MS (EI,
70 eV), m/z (%): 355 (Mþ, 31), 338 (52), 308 (52), 259 (45), 229 (32),
200(100), 189 (38), 100 (73).
4.2.5. 2-(3-Chlorophenyl)-3-nitro-1-naphthaldehyde (3e). Light yel-
low solid, mp 166e167 ꢀC; 1H NMR (CDCl3, 400 MHz)
d 10.00 (s,
All 1H and 13C NMR spectra were recorded using a Bruker
1H), 9.12 (d, J¼8.4 Hz, 1H), 8.61 (s, 1H), 8.06 (d, J¼8.4 Hz, 1H),
7.88e7.84 (m, 1H), 7.75 (t, J¼7.6 Hz, 1H), 7.49 (d, J¼8.0 Hz, 1H), 7.43
(t, J¼7.6 Hz, 1H), 7.38 (s, 1H), 7.26 (d, J¼6.0 Hz, 1H); 13C NMR (CDCl3,
400 MHz and 100 MHz spectrometers. Chemical shifts (d) are given
in parts per million, and coupling constants (J) are given in hertz
(Hz). Melting points were determined on an uncorrected XT-4
melting point apparatus. MS was measured on a VG-7070E spectro-
meter (EI at 70 eV). IR spectra were recorded using Nicolet NEXUS
670 FTIR instrument. Starting materials 1 were prepared according
to the published methods,10 the Experimental procedure and
characterization data are available in the Supplementary data.
100 MHz) d 192.6, 147.1, 137.2, 134.8, 134.6, 132.3, 132.0, 131.8, 131.2,
129.8, 129.7, 129.6, 129.4, 129.2, 128.9, 128.1, 126.1; IR (KBr): 3399,
2924, 1692, 1530, 1344, 1060, 763 cmꢁ1; MS (EI, 70 eV), m/z (%): 311
(Mþ, 23), 294 (75), 264 (100), 236 (24), 200 (68), 189 (21), 100 (47).
4.2.6. 2-(4-Chlorophenyl)-3-nitronaphthalene-1-carbaldehyde
(3f). Light yellow solid, mp 129e130 ꢀC; 1H NMR (CDCl3, 400 MHz)
4.2. General experimental procedure for synthesis of poly-
substituted naphthalene derivatives
d
9.99 (s, 1H), 9.10 (d, J¼8.8 Hz, 1H), 8.58 (s, 1H), 8.05 (d, J¼8.0 Hz,
1H), 7.87e7.83 (m, 1H), 7.76e7.72 (m, 1H), 7.49e7.46 (m, 2H),
7.32e7.29 (m, 2H); 13C NMR (CDCl3, 100 MHz)
192.7, 147.4, 137.4,
d
2-(2-Oxoethyl)benzaldehyde 1 (0.4 mmol) was added to a mix-
ture of nitroalkene 2 (0.2 mmol), pyrrolidine (0.04 mmol), and
DMAP (0.04 mmol) in CH2Cl2 and water (2.0 mL, VDCM/Vwater¼1:1) at
0 ꢀC. The reaction mixture was stirred at 0 ꢀC for 4 h, and then it was
stirred vigorously at room temperature until the intermediate was
consumed as monitored by TLC. The mixture was extracted with
CH2Cl2. The combined organic fractions were washed with brine,
dried over anhydrous Na2SO4, and concentrated under reduced
pressure. The residue was purified by flash column chromatography
on silica gel (PE/EtOAc) to afford the corresponding naphthalene 3.
135.6, 132.2, 131.9, 131.8, 131.2, 131.1, 129.5, 129.0, 128.9, 128.8,
126.0; IR (KBr): 3743, 3361, 2920, 1686, 1529, 1335, 1058, 854,
762 cmꢁ1; MS (EI, 70 eV), m/z (%): 311 (Mþ, 37), 294 (70), 264 (100),
236 (17), 200 (68), 189 (18), 100 (39).
4.2.7. 3-Nitro-2-(3-nitrophenyl)naphthalene-1-carbaldehyde
(3g). Light yellow solid, mp 199e200 ꢀC; 1H NMR (DMSO-d6,
400 MHz)
8.39e8.36 (m, 3H), 7.99e7.93 (m, 2H), 7.89e7.80 (m, 2H); 13C NMR
(DMSO-d6, 100 MHz) 193.0, 147.5, 146.5, 136.4, 135.1, 135.0, 132.4,
d
9.97 (s, 1H), 9.15 (s, 1H), 8.95 (d, J¼8.8 Hz, 1H),
d
131.9, 131.7, 130.7, 130.3, 129.9, 129.7, 129.0, 125.2, 124.4, 123.7; IR
(KBr): 3416, 2920, 1957, 1678, 1526, 1340, 1212, 716 cmꢁ1; MS (EI,
70 eV), m/z (%): 322 (Mþ, 27), 305 (99), 275 (66), 229 (49), 200
(100), 189 (41), 176 (18), 100 (29).
4.2.1. 3-Nitro-2-phenylnaphthalene-1-carbaldehyde (3a). Light yel-
low solid, mp 158e159 ꢀC; 1H NMR (CDCl3, 400 MHz)
d 9.98 (s, 1H),
9.13 (d, J¼8.8 Hz, 1H), 8.55 (s, 1H), 8.04 (d, J¼8.0 Hz, 1H), 7.86e7.82
(m, 1H), 7.75e7.71 (m, 1H), 7.50e7.48 (m, 3H), 7.38e7.36 (m, 2H);
13C NMR (CDCl3, 100 MHz)
d
193.1, 147.7, 138.8, 132.6, 132.0, 131.8,
4.2.8. 3-Nitro-2-(4-nitrophenyl)naphthalene-1-carbaldehyde
131.7, 131.2, 129.9, 129.4, 129.2, 128.7, 128.6, 128.5, 126.0; IR (KBr):
3365, 2879, 1685, 1527, 1057, 756 cmꢁ1; MS (EI, 70 eV), m/z (%): 277
(Mþ, 22), 260 (89), 230 (100), 202 (83), 189 (17), 176(10), 88 (21).
(3h). Light yellow solid, mp 182e183 ꢀC; 1H NMR (CDCl3, 400 MHz)
d
10.00 (s, 1H), 9.10 (d, J¼8.8 Hz, 1H), 8.74 (s, 1H), 8.38 (d, J¼8.4 Hz,
2H), 8.12 (d, J¼7.6 Hz, 1H), 7.93e7.89 (m, 1H), 7.80 (t, J¼7.6 Hz, 1H),
7.58 (d, J¼8.4 Hz, 2H); 13C NMR (CDCl3, 100 MHz)
d 191.8, 148.2,
4.2.2. 2-(2-Bromophenyl)-3-nitronaphthalene-1-carbaldehyde
146.3, 140.1, 136.1, 132.7, 132.2, 131.8, 131.3, 130.8129.8, 129.7, 129.3,
126.1,123.7; IR (KBr): 3403,1933,1526,1343,1111, 711 cmꢁ1; MS (EI,
70 eV), m/z (%): 322 (Mþ,14), 305 (66), 275 (21), 229 (35), 200 (100),
189 (46), 176 (18), 100 (35).
(3b). Light yellow solid, mp 112e113 ꢀC; 1H NMR (CDCl3, 400 MHz)
d
9.98 (s, 1H), 9.17 (d, J¼8.4 Hz, 1H), 8.78 (s, 1H), 8.09 (d, J¼8.4 Hz,
1H), 7.89e7.86 (m, 1H), 7.80e7.72 (m, 2H), 7.45 (t, J¼7.2 Hz, 1H),
7.39e7.32 (m, 2H); 13C NMR (CDCl3, 100 MHz)
192.6, 146.2, 138.0,
d
134.4, 132.8, 132.4, 132.2, 131.6, 131.5, 131.3, 130.6, 130.0, 129.8,
128.9, 127.5, 126.2, 123.8; IR (KBr): 3373, 3068, 2957, 2869, 1694,
4.2.9. 4-(1-Formyl-3-nitronaphthalen-2-yl) benzonitrile (3i). Light
yellow solid, mp 158e159 ꢀC; 1H NMR (CDCl3, 400 MHz)
d 9.98 (s,

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S.-G. Li et al. / Tetrahedron 66 (2010) 8557e8561
1H), 9.09 (d, J¼8.8 Hz, 1H), 8.70 (s, 1H), 8.10 (d, J¼8.0 Hz, 1H),
7.92e7.88 (m, 1H), 7.79 (t, J¼8.8 Hz, 3H), 7.51 (d, J¼8.4 Hz, 2H); 13C
(EI, 70 eV), m/z (%): 355 (Mþ, 20), 338 (62), 310 (62), 229 (14), 200
(100), 189 (28), 150 (16), 100 (73).
NMR (CDCl3, 100 MHz) d 191.9, 146.5, 138.1, 136.5, 132.7, 132.2, 132.1,
131.7, 131.3, 130.5, 129.8, 129.7, 129.2, 126.1, 118.0, 113.2; IR (KBr):
3404, 3075, 2223, 1681, 1525, 1335, 1054, 859, 747 cmꢁ1; MS (EI,
70 eV), m/z (%): 302 (Mþ,18), 285 (69), 255 (100), 227 (70), 200 (19),
125 (11), 100 (32), 87 (20).
4.2.16. 6-Bromo-2-(3-bromophenyl)-3-nitronaphthalene-1-carbal-
dehyde (3p). Light yellow solid, mp 114e115 ꢀC; 1H NMR (CDCl3,
400 MHz)
d
9.97 (s, 1H), 9.03 (d, J¼9.6 Hz, 1H), 8.49 (s, 1H), 8.22 (d,
J¼2.0 Hz,1H), 7.91 (dd, J¼2.0, 9.6 Hz,1H), 7.66 (d, J¼8.0 Hz,1H), 7.53
(d, J¼2.0 Hz, 1H), 7.38 (t, J¼7.6 Hz, 1H), 7.31 (d, J¼7.6 Hz, 1H); 13C
4.2.10. 3-Nitro-2-p-tolylnaphthalene-1-carbaldehyde (3j). Light yel-
NMR (CDCl3, 100 MHz) d 192.1, 148.0,137.3,135.5,134.3, 133.1, 132.6,
low solid, mp 120e121 ꢀC; 1H NMR (CDCl3, 400 MHz)
d
9.98 (s, 1H),
132.5, 131.8, 131.3, 130.1, 129.6, 128.5, 127.8, 123.6, 122.9; IR (KBr):
3366, 3114, 2920, 1694, 1531, 1344, 909, 725 cmꢁ1; MS (EI, 70 eV),
m/z (%): 433 (Mþ, 8), 418 (40), 388 (34), 339 (21), 309 (16), 281(9),
200 (100), 150 (12), 100 (80).
9.13 (dd, J¼0.8, 8.8 Hz, 1H), 8.52 (s, 1H), 8.03 (d, J¼8.0 Hz, 1H),
7.85e7.81 (m, 1H), 7.74e7.70 (m, 1H), 7.29 (d, J¼8.0 Hz, 2H), 7.25 (d,
J¼8.0 Hz, 2H), 2.44 (s, 3H); 13C NMR (CDCl3, 100 MHz)
d 193.3, 148.0,
139.3, 138.9, 131.9, 131.8, 131.7, 131.2, 129.8, 129.5, 129.4, 129.3, 129.2,
128.5, 126.0, 21.3; IR (KBr): 3363, 2921, 1690, 1530, 1347, 1059,
755 cmꢁ1; MS (EI, 70 eV), m/z (%): 291 (Mþ, 53), 274 (100), 244 (90),
215 (84), 202 (46), 189 (31), 107 (18), 95 (22).
4.2.17. 6-Bromo-2-(4-bromophenyl)-3-nitronaphthalene-1-carbal-
dehyde (3q). Light yellow solid, mp 132e133 ꢀC; 1H NMR (CDCl3,
400 MHz)
d
9.96 (s, 1H), 9.01 (d, J¼9.6 Hz, 1H), 8.47 (s, 1H), 8.21 (d,
J¼1.6 Hz, 1H), 7.91 (dd, J¼1.6, 9.6 Hz, 1H), 7.65 (d, J¼8.4 Hz, 2H), 7.24
4.2.11. 2-(2-Methoxyphenyl)-3-nitro-1-naphthaldehyde (3k). Light
(d, J¼8.4 Hz, 2H); 13C NMR (CDCl3, 100 MHz)
d 192.2, 148.1, 137.6,
yellow solid, mp 135e136 ꢀC; 1H NMR (CDCl3, 400 MHz)
d
9.97 (s,
135.4, 133.1, 132.0, 131.9, 131.3, 131.2, 131.1, 129.6, 127.8, 127.6, 124.1,
123.5; IR (KBr): 3367, 3110, 2923, 1693, 1531, 1484, 1344, 1073,
824 cmꢁ1; MS (EI, 70 eV), m/z (%): 433 (Mþ, 11), 418 (31), 388 (30),
339 (21), 309 (18), 281(7), 200 (100), 189 (17), 150 (12), 100 (70).
1H), 9.13 (d, J¼8.8 Hz, 1H), 8.63 (s, 1H), 8.05 (d, J¼8.4 Hz, 1H),
7.84e7.80 (m, 1H), 7.73e7.69 (m, 1H), 7.51e7.47 (m, 1H), 7.21 (dd,
J¼1.6, 7.6 Hz, 1H), 7.10 (t, J¼7.6 Hz, 1H), 7.01 (d, J¼8.4 Hz, 1H), 3.74
(s, 3H); 13C NMR (CDCl3, 100 MHz)
d 193.5,156.5,147.5,136.0, 132.2,
131.8, 131.7, 131.7, 131.6, 131.0, 129.5, 128.9, 128.4, 125.9, 121.7,
120.9, 110.8, 55.5; IR (KBr): 3401, 2932, 1690, 1529, 1345, 1020,
758 cmꢁ1; MS (EI, 70 eV), m/z (%): 307 (Mþ, 99), 290 (60), 273 (62),
245 (48), 231 (68), 217 (50), 202 (34), 189 (100), 163 (25), 95 (50).
4.2.18. 7-Bromo-3-nitro-2-phenylnaphthalene-1-carbaldehyde
(3r). Light yellow solid, mp 152e153 ꢀC; 1H NMR (CDCl3, 400 MHz)
d
9.93 (s, 1H), 9.41 (s, 1H), 8.52 (s, 1H), 7.90 (d, J¼8.4 Hz, 1H), 7.82
(dd, J¼1.6, 8.4 Hz, 1H), 7.52e7.50 (m, 3H), 7.37e7.35 (m, 2H); 13C
NMR (CDCl3, 100 MHz)
d 192.5, 148.0, 140.1, 132.4, 132.1, 132.0,
4.2.12. 2-(Furan-2-yl)-3-nitronaphthalene-1-carbaldehyde
130.6, 130.3, 129.9, 129.5, 128.7, 128.6, 128.5, 127.6; IR (KBr): 3092,
2921, 2853, 1962, 1863, 1767, 1680, 1586, 1535, 1482, 1337, 1200,
1055, 892, 806, 707, 661, 492 cmꢁ1; MS (EI, 70 eV), m/z (%): 355 (Mþ,
10), 338 (66), 310 (58), 229 (40), 200 (100), 189(73), 149 (53), 100
(75), 57 (86), 40 (93).
(3l). Light yellow solid, mp 105e106 ꢀC; 1H NMR (CDCl3, 400 MHz)
d
10.08 (s, 1H), 9.00 (d, J¼8.8 Hz, 1H), 8.55 (s, 1H), 8.03 (d, J¼8.4 Hz,
1H), 7.85e7.81 (m, 1H), 7.75e7.65 (m, 1H), 7.64 (s, 1H), 6.69e6.62
(m, 2H); 13C NMR (CDCl3, 100 MHz)
192.2, 146.4, 145.1, 143.5,
132.8, 132.0, 131.9, 130.8, 129.6, 129.1, 129.0, 126.5, 126.0, 116.6,
d
111.9; IR (KBr): 3343, 2867, 1680, 1531, 1349, 1215, 1013, 756 cmꢁ1
;
4.2.19. 8-Methyl-3-nitro-2-phenyl-1,2-dihydronaphthalene-1-car-
MS (EI, 70 eV), m/z (%): 267 (Mþ, 7), 238 (6), 222 (35), 194 (25), 166
baldehyde (8s). Light yellow oil. 1H NMR (CDCl3, 400 MHz)
d 9.55 (s,
(100), 152 (94), 139 (78), 126 (72).
1H), 8.01 (s, 1H), 7.38e7.34 (m, 3H), 7.21 (t, J¼3.2 Hz, 3H), 7.11e7.09
(m, 2H), 5.08 (s, 1H), 4.16 (s, 1H), 2.29 (s, 3H); 13C NMR (CDCl3,
4.2.13. 6-Methyl-3-nitro-2-phenylnaphthalene-1-carbaldehyde
100 MHz) d 195.5,148.2,138.3,137.8,134.6,131.6,130.2,129.2,129.0,
(3m). Light yellow solid, mp 153e154 ꢀC; 1H NMR (CDCl3,
128.9, 127.9, 127.8, 126.9, 57.1, 38.1, 19.4; IR (KBr): 3425, 3065, 2826,
2725, 2255, 1952, 1878, 1721, 1648, 1516, 1466, 1324, 1257, 1062,
1027, 930, 910, 789, 733, 700, 590 cmꢁ1; MS (EI, 70 eV), m/z (%): 293
(Mþ, 31), 276 (100), 246 (83), 217 (79), 204 (43), 191 (29), 97 (20).
400 MHz)
1H) 7.66 (d, J¼8.8 Hz, 1H), 7.49e7.48 (m, 3H), 7.37e7.35 (m, 2H),
2.59 (s, 3H); 13C NMR (CDCl3, 100 MHz)
193.3, 147.8, 138.9, 138.0,
d
9.96 (s, 1H), 9.02 (d, J¼8.8 Hz, 1H), 8.45 (s, 1H), 7.79 (s,
d
134.3, 132.7, 132.1, 131.4, 129.9, 129.4, 129.0, 128.5, 128.3, 128.1,
125.7, 21.5; IR (KBr): 3401, 1956, 1677, 1523, 1328, 1214, 1055, 820,
704 cmꢁ1; MS (EI, 70 eV), m/z (%): 291 (Mþ, 41), 274 (100), 244 (97),
215 (76), 202 (43), 189 (27), 139 (11), 95 (26).
4.3. General experimental procedure for synthesis of (3-
amino-2-phenylnaphthalen-1-yl)methanol 9
NaBH4 (31 mg, 0.81 mmol) was added in portions to a solution of
3a (150 mg, 0.54 mmol) in MeOH (5 mL) at 0 ꢀC. The mixture was
stirred for 30 min, diluted with water (10 mL), and extracted with
EtOAc. The organic layer was dried over NaSO4 and the solvent was
removed under reduced pressure. The crude alcohol was resus-
pended in ethanol (12 mL) and treated with H2O (3 mL), iron dust
(287 mg, 5.1 mmol), and a catalytic amount of concentrated
hydrochloric acid. The mixture was stirred at reflux for 30 min, and
filtered to remove iron dust. The filtrate was concentrated to one-
fifth of its original volume, and extracted with EtOAc. The combined
organic fractions were washed with brine, dried over anhydrous
Na2SO4, and concentrated under reduced pressure. The residue was
purified by flash column chromatography on silica gel (PE/EtOAc) to
afford 9 as a brown liquid. Yield, 82 mg (64%). 1H NMR (CDCl3,
4.2.14. 2-(3-Bromophenyl)-6-methyl-3-nitronaphthalene-1-carbal-
dehyde (3n). Light yellow solid, mp 162e163 ꢀC; 1H NMR (CDCl3,
400 MHz)
1H), 7.70e7.62 (m, 2H), 7.53 (t, J¼1.6 Hz,1H), 7.38e7.30 (m, 2H), 2.60
(s, 3H); 13C NMR (CDCl3, 100 MHz)
192.7, 147.1, 139.3, 136.3, 135.0,
d
9.99 (s, 1H), 9.02 (d, J¼8.8 Hz, 1H), 8.53 (s, 1H), 7.82 (s,
d
134.7, 132.6, 132.3, 132.2, 131.5, 129.9, 129.5, 128.6, 128.6, 128.5,
125.8, 122.8, 21.5; IR (KBr): 3355, 3063, 1685, 1526, 1343, 1217, 829,
690 cmꢁ1; MS (EI, 70 eV), m/z (%): 369 (Mþ, 21), 352 (48), 322 (37),
273 (42), 243 (30), 215 (100), 189 (29), 139 (15), 107 (35), 95 (43).
4.2.15. 6-Bromo-3-nitro-2-phenylnaphthalene-1-carbaldehyde
(3o). Light yellow solid, mp 172e173 ꢀC; 1H NMR (CDCl3, 400 MHz)
d
9.94 (s, 1H), 9.03 (d, J¼9.2 Hz, 1H), 8.42 (s, 1H), 8.19 (d, J¼2.0 Hz,
1H), 7.88 (dd, J¼2.0 Hz, 9.2 Hz, 1H), 7.52e7.48 (m, 3H), 7.37e7.35
(m, 2H); 13C NMR (CDCl3, 100 MHz)
192.7, 148.6, 139.0, 135.2,
400 MHz)
d
8.11 (d, J¼8.4 Hz, 1H), 7.64 (d, J¼8.4 Hz, 1H), 7.51 (t,
d
J¼7.2 Hz, 2H), 7.46e7.39 (m, 2H), 7.34e7.30 (m, 3H), 7.07 (s, 1H),
132.9, 132.1, 131.7, 131.1, 129.8, 129.6, 129.4, 128.7, 127.7, 127.3, 123.2;
IR (KBr): 3405, 3073, 2924, 1949, 1683, 1529, 1050, 698 cmꢁ1; MS
4.77 (s, 2H), 3.61 (s, 2H), 1.60 (s, 1H); 13C NMR (CDCl3, 100 MHz)
d
142.3, 137.0, 134.8, 134.5, 131.2, 129.9, 129.1, 128.0, 126.3, 126.2,

S.-G. Li et al. / Tetrahedron 66 (2010) 8557e8561
8561
124.4, 123.2, 109.2, 59.8; IR (KBr): 3551, 3469, 3372, 3055, 2923,
References and notes
1952, 1726, 1624, 1501, 1447, 1384, 1272, 1064, 983, 869, 750, 704,
663 cmꢁ1; MS (EI, 70 eV), m/z (%): 249 (Mþ, 35), 220 (26), 202 (8),
149 (5), 115 (12), 97 (7), 57 (13), 45 (100).
1. Some representative examples from this century include: (a) Dalton King, H.;
Denhart, D. J.; Deskus, J. A.; Ditta, J. L.; Epperson, J. R.; Higgins, M. A.; Kung, J. E.;
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4.4. General experimental procedure for synthesis of (3-
azido-2-phenylnaphthalen-1-yl)methanol 10
A solution of NaNO2 (11 mg, 0.16 mmol) in water was added
dropwise to a solution of 9 (40 mg, 0.16 mmol) in THF (3 mL) and
10% HCl (3 mL) at 0e5 ꢀC with vigorous stirring. The mixture was
kept below 5 ꢀC for 30 min, and then a solution of NaN3 (15.6 mg,
0.24 mmol) in water (3 mL) was added dropwise while the tem-
perature was kept below 5 ꢀC. After being stirred for 1 h, the re-
action mixture was allowed to reach at room temperature, then it
was extracted with EtOAc. The extract was dried over anhydrous
Na2SO4, and concentrated under reduced pressure. The residue was
purified by flash column chromatography on silica gel (PE/EtOAc) to
afford 10 as a brown liquid. Yield, 39 mg (90%). 1H NMR (CDCl3,
€
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400 MHz)
7.56e7.53 (m, 2H), 7.48e7.44 (m, 3H), 7.29e7.25 (m, 2H), 4.82 (s,
2H), 1.61 (s, 1H); 13C NMR (CDCl3, 100 MHz)
136.8, 136.6, 135.8,
d
8.24 (t, J¼3.2 Hz, 1H), 7.85e7.81 (m, 1H), 7.60 (s, 1H),
d
133.9, 133.7, 130.0, 129.8, 128.2, 127.9, 127.3, 126.9, 126.4, 124.8,
116.0, 59.5; IR (KBr): 3568, 3355, 3057, 2897, 2246, 2111, 1590, 1433,
1339, 1291, 1243, 1027, 1008, 909, 843, 746, 704, 652, 540 cmꢁ1; MS
(EI, 70 eV), m/z (%): 275 (Mþ, 2), 229 (37), 217 (31), 189 (8), 149 (4),
114 (8), 84 (17), 61 (13), 43 (100).
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Acknowledgements
We are grateful for the National Basic Research Program of China
(No. 2009CB626604), the NSFC (20772051, 20972058), the ‘111’
program from MOE of PR China and the Fund from Gansu Province
(096RJZA064).
Supplementary data
9. (a) Wang, X.-S.; Li, Q.; Zhang, M.-M.; Yao, C.-S.; Tu, S.-J. J. Heterocycl. Chem.
2008, 45, 1027; (b) Wu, Y.-C.; Liu, L.; Li, H.-J.; Wang, D.; Chen, Y.-J. J. Org. Chem.
2006, 71, 6592; (c) Eisch, J.-J.; Dluzniewski, T. J. Org. Chem. 1989, 54, 1269.
10. (a) Frank, M. H.; Subbarao, P. Synthesis 1980, 621; (b) Garratt, P. J.; Vollhardt, K.
P. C. Synthesis 1971, 423.
Experimental procedures, NMR spectra data for new compounds
analyses are available in the Supplementary data. Supplementary
data associated with this article can be found in the online version, at
doi:10.1016/j.tet.2010.08.069. These data include MOL files and
InChIKeys of the most important compounds described in this article.
11. Masayuki, T.; Shoko, S.; Shozo, K. Chem. Pharm. Bull. 1982, 3125.