Cu(i)-catalyzed annulation for the synthesis of substituted naphthalenes using o-bromobenzaldehydes and β-ketoesters as substrates

Article abstract of DOI:10.1039/c2ob06963f

Cu(i)-catalyzed reaction of o-bromobenzaldehydes with β-ketoesters using Cs₂CO₃ as a base and 2-picolinic acid as an additive proceeds under mild conditions and gives access to substituted naphthalenes in a single step with yields ra

Full text of DOI:10.1039/c2ob06963f

View Article Online / Journal Homepage / Table of Contents for this issue
Dynamic Article Links
Organic &
Biomolecular
Chemistry
Cite this: Org. Biomol. Chem., 2012, 10, 3899
www.rsc.org/obc
PAPER
Cu(I)-catalyzed annulation for the synthesis of substituted naphthalenes using
o-bromobenzaldehydes and β-ketoesters as substrates†
Chandi C. Malakar, Kavitha Sudheendran, Hans-Georg Imrich, Sabine Mika and Uwe Beifuss*
Received 22nd November 2011, Accepted 9th March 2012
DOI: 10.1039/c2ob06963f
Cu(I)-catalyzed reaction of o-bromobenzaldehydes with β-ketoesters using Cs2CO3 as a base and
2-picolinic acid as an additive proceeds under mild conditions and gives access to substituted
naphthalenes in a single step with yields ranging from 71 to 86%. The new annulation process relies on a
domino Knoevenagel condensation/C-arylation/1,2-addition/carboxylic acid cleavage. The annulation can
also be achieved with o-iodobenzaldehyde.
light emitting diodes, organic semiconductors and luminescent
Introduction
materials due to their unique photochemical and electrochemical
properties.9
Modern organic synthesis is unthinkable without Cu-catalyzed
bond forming reactions as they are not restricted to the efficient
construction of carbon–heteroatom bonds like C,N-, C,O- and C,
S-bonds but also allow for the synthesis of C,C-bonds.1 Among
the most well known Cu(I)-catalyzed transformations are the
reactions between (hetero)aryl halides and N-, O- and S-nucleo-
philes. In the past this type of reaction could only be achieved
under harsh reaction conditions but meanwhile protocols have
been improved considerably. This allows such reactions to be
performed under comparable mild conditions. The scope of
Cu(I)-catalyzed reactions can be extended substantially when bis-
functionalized (hetero)arenes are used as substrates in domino
type processes.2 This approach allows the synthesis of numerous
heterocycles. Typical examples include the reactions of o-di-
haloarenes,3 o-haloanilines,4 o-haloanilides5 and o-halobenza-
mides6 with suitable reaction partners. Recently, we have found
that the reaction of o-bromobenzyl bromides with β-ketoesters
can be used for the efficient preparation of 4H-chromenes.7 We
have proposed that this transformation proceeds as a C-benzyla-
tion/O-arylation process. In contrast to numerous examples
known for the synthesis of heterocycles, Cu(I)-catalyzed pro-
cesses have only rarely been exploited for the preparation of
carbocycles.8
This is why there is continuing interest in the development of
efficient methods for the construction of bicyclic and polycyclic
aromatic compounds. Annulations are particular attractive
because of the ease with which a great variety of aromatic
systems can be synthesized. Among the best known annulations
for the synthesis of aromatic rings are the 4 + 2 and the 2 + 2 +
2 annulations. The 4 + 2 annulations can be achieved by Diels-
Alder reactions of o-quinodimethanes with acetylenic dieno-
philes10 and of benzynes with dienes.11 In addition, a number of
transition metal based 4 + 2 annulations have been developed
which include the Pd-catalyzed reaction between arene contain-
ing vinylic iodides and triflates with internal alkynes,12 the Pd-
catalyzed reaction of o-(2-alkenyl)aryl halides with 1,2-disubsti-
tuted alkynes,13 the Rh-catalyzed reaction of an arylalkyne with
an alkylalkyne,14 the Au-catalyzed annulation of arylacetalde-
hydes with alkynes15 or the reaction of o-dihaloarenes with zir-
conacyclopentadienes.16 The 2 + 2 + 2 annulations have been
performed by the Ir-catalyzed reaction of aroyl chlorides17a or
benzoic acids17b with internal alkynes, the Ni-catalyzed reaction
of o-diiodoarenes with alkynes,18 the Pd-catalyzed reaction of
o-diiodoarenes with alkynes,19 the Pd-catalyzed cocyclization of
benzynes with alkynes,20 the Pd-catalyzed treatment of arenes
with alkynes21 and the Rh-catalyzed treatment of arenes with
alkynes.22
Highly substituted bicyclic and polycyclic aromatic com-
pounds are common structural motifs of natural products and
pharmaceuticals. In recent years such aromatic systems have
attracted considerable attention for the construction of organic
Despite numerous approaches, the preparation of annulated
aromatic systems bearing different substituents at specific pos-
itions employing easily available starting materials is far from
being well established.
Recently, we have developed a new synthetic route towards
substituted naphthalenes that relies on the Cu(I)-catalyzed reac-
tion of an o-halobenzyl halide, preferably an o-bromobenzyl
bromide, with two molecules of a β-ketoester (Scheme 1).7 In
this naphthalene synthesis three C,C-bonds are formed in one
Bioorganische Chemie, Institut für Chemie, Universität Hohenheim,
Garbenstr. 30, D-70599 Stuttgart, Germany. E-mail: ubeifuss@
uni-hohenheim.de; Fax: +(49) 0711 459-22951;
Tel: +(49) 0711 459-22171
†Electronic supplementary information (ESI) available: 1H and 13C
spectra of all compounds. See DOI: 10.1039/c2ob06963f
This journal is © The Royal Society of Chemistry 2012
Org. Biomol. Chem., 2012, 10, 3899–3905 | 3899

View Article Online
Scheme 1 Cu(I)-catalyzed synthesis of substituted naphthalenes by
reaction of a 2-halobenzyl halide with two molecules of a β-ketoester.7
Scheme 3 Proposed mechanism for the reaction of o-bromobenzalde-
hyde Awith β-ketoesters B.
Scheme 2 Initial experiment for the Cu(I)-catalyzed reaction of o-bro-
mobenzaldehyde (1a) with ethyl acetoacetate (2a).
Table 1 Optimization of the reaction between 1a and 2aa,b
synthetic operation. The approach is unique in the sense that
three C-atoms of the newly formed aromatic ring stem from the
o-halobenzyl halide, two from the first β-ketoester molecule and
one C-atom from the second β-ketoester. So far the method has
been restricted to o-halobenzyl halides as starting materials. Here
we report that the new approach to annulated aromatic systems
can be extended to o-halobenzaldehydes as substrates. o-Halo-
benzaldehydes are particular attractive starting materials as they
can easily be obtained by numerous synthetic methods.23
Entry
4 (mol %)
T (°C)
t (h)
Solvent
3a Yield (%)
1
2
3
4
5
6
7
30
30
15
—
30
30
30
100
100
100
100
60
60
60
24
24
24
24
40
40
40
NMP
DMF
DMF
DMF
DMF
DMF
DMF
36
62
23
11
71
46c
45d
Results and discussion
a Unless otherwise indicated, all reactions were performed using
0.5 mmol of 1a and 1.5 mmol of 2a in a sealed vial. b On the TLC
traces of a side product with a higher Rf-value than 3a was observed.
c Reaction was performed using 1 mmol of 2a. d Reaction was carried
out under air.
We started with the reaction between o-bromobenzaldehyde (1a)
with ethyl acetoacetate (2a) under the reaction conditions that
had been proven successful for the reaction of o-bromobenzyl
bromides with β-ketoesters.7 Reaction of 1 equiv. 1a with 3
equivs. of 2a in the presence of 10 mol% CuI, 30 mol% 2-picoli-
nic acid (4) and 4 equivs. Cs2CO3 at 100 °C for 24 h in N-
methyl pyrrolidine delivered the expected naphthalene 3a in
40% yield (Scheme 2).
This result clearly demonstrated that the annulation can also
be achieved by using an o-bromobenzaldehyde as a substrate.
However, it was obvious that the yield had to be improved sub-
stantially to make this an interesting synthetic method. There-
fore, the reaction had to be optimized.
We propose that the annulation starts with a Knoevenagel con-
densation between the o-bromobenzaldehyde and the β-ketoester
(A + B → C) (Scheme 3). This is followed by an intermolecular
C-arylation of a second β-ketoester (C + B → D) and an intra-
molecular 1,2-addition (D → E). The final step of the sequence
is the cleavage of the carboxylic acid (E → F → G).
During the first step of the reaction cascade, the Knoevenagel
condensation, one equivalent of water is formed which might
interfere with some of the following reaction steps of the
sequence. Therefore, all further reactions were run in the pres-
ence of molecular sieves 4 Å to remove the water formed from
the reaction mixture during the Knoevenagel condensation.
However, with NMP as a solvent this measure did not pay off.
But when NMP was replaced by DMF the yield of 3a improved
by 26% to 62% (Table 1, entry 1 and 2). Reduction of the
amount of 2-picolinic acid (4) from 30 mol% to 15 mol% led to
a substantial decrease of the yield to 23%, and when the reaction
was performed in the absence of any 2-picolinic acid (4) only
11% of 3a could be isolated (Table 1, entry 3 and 4). This
clearly demonstrates that an additive like 4 which is believed to
activate the CuI by complexation is necessary to guarantee high
yields of the naphthalene. A further increase of the yield of 3a to
71% could be achieved when the reaction was performed at
60 °C for 40 h (Table 1, entry 5). It was also found that the reac-
tion needs to be performed with 3 equivs. 2a and in the absence
of oxygen (Table 1, entry 6 and 7).
Further experiments revealed that a reduction of the amount of
CuI from 10 mol% to 5 mol% and 1 mol%, respectively, led to a
decrease of the yield of 3a from 71% to 39% and 21%, respect-
ively (Table 1, entry 5 and Table 2, entry 1 and 2). Apart from
3900 | Org. Biomol. Chem., 2012, 10, 3899–3905
This journal is © The Royal Society of Chemistry 2012

View Article Online
Table 2 The influence of different Cu-sources on the outcome of the
reaction of 1a with 2aa,b
Scheme 4 o-Iodobenzaldehyde (1b) as substrate for the synthesis of
naphthalene 3a.
Entry
Cu-source (mol%)
3a Yield (%)
1
2
3
4
5
6
7
8
CuI; 5
CuI; 1
39
21
54
61
29
23
35
—
revealed that the model reaction of 1a with 2a could also be per-
formed in other solvents than DMF, but only at the cost of lower
yields of 3a (Table 3, entry 3–6).
The optimization of the model reaction of 1a and 2a with
regard to the Cu-source, the base, the additive, the solvent and
the reaction conditions clearly demonstrated that the highest
yield of 3a was obtained when 1 equiv. of 1a and 3 equivs. of
2a were reacted in the presence of 10 mol% CuI, 30 mol% 2-
picolinic acid (4) and 4 equivs. Cs2CO3 in DMF at 60 °C for
40 h using molecular sieves (4 Å) as a drying agent.
CuBr; 10
CuCl; 10
CuOTf (MeCN)4; 10
Cu(OAc)2; 10
Cu2O; 10
—
a All reactions were performed using 0.5 mmol of 1a and 1.5 mmol of
2a in a sealed vial. b On the TLC traces of a side product with a higher
Rf-value than 3a was observed.
It was also studied whether the annulation can be performed
using o-iodobenzaldehyde (1b) and o-chlorobenzaldehyde (1c)
as the substrates. For this purpose, the reaction between o-iodo-
benzaldehyde (1b) and ethyl acetoacetate (2a) was performed
under the reaction conditions that had proven successful for the
reaction of 1a with 2a. It turned out that 3a could be obtained
with 73% yield (Scheme 4). Next, o-chlorobenzaldehyde (1c)
was reacted with 2a under a number of reaction conditions (see
ESI†). However, in no case was the formation of 3a observed.
This is in agreement with the fact that, so far, the Cu-catalyzed
reaction between chlorobenzene and β-ketoesters has not been
achieved.
Table 3 The influence of different bases and solvents on the Cu(I)-
catalyzed reaction of 1a with 2aa,b
Entry
Base (4 equiv.)
Solvent
3a Yield (%)
With the optimized reaction conditions the scope of the new
three component reaction was investigated. It could be shown
that numerous o-bromobenzaldehydes 1a,d–f with different sub-
stitution patterns can be reacted with a number of β-ketoesters
2a–d to produce the corresponding substituted naphthalenes
3a–i with yields ranging from 71 to 86% (Table 4).
The new process using o-bromobenzaldehydes displays a
number of advantages over the method using o-bromobenzyl
bromides as substrates: (i) In contrast to benzyl bromides the cor-
responding benzaldehydes have no lachrymatory properties, (ii)
the reaction temperatures are much lower and the yields of the
naphthalenes are higher.
1
2
3
4
5
6
K3PO4
DMF
DMF
NMP
MeCN
THF
61
26
32
51
38
9
K2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
iso-PrOH
a All reactions were performed using 0.5 mmol of 1a and 1.5 mmol of
2a in a sealed vial. b On the TLC traces of a side product with a higher
Rf-value than 3a was observed.
CuI, a number of other Cu compounds were tried as catalysts. It
was found that the reaction of 1a with 2a using 10 mol% of
CuBr or 10 mol% of CuCl as catalysts also resulted in the selec-
tive formation of 3a in 54% and 61% yield, respectively
(Table 2, entry 3 and 4). However, the yields were lower
than with CuI and the same holds true for the use of
CuOTf (MeCN)4, Cu2O and Cu(OAc)2 as catalysts (Table 2,
entry 5–7). It should be noted that in the absence of any
Cu-source no formation of 3a was observed (Table 2, entry 8).
Finally, the influence of different bases and solvents on the Cu
(I)-catalyzed reaction of 1a with 2a was studied. It was found
that the reaction using 4 equiv. of K3PO4 as a base selectively
delivered the product 3a in 61% yield (Table 3, entry 1). Even
with K2CO3 as a base the reaction took place, but the yield of 3a
amounted to only 26% (Table 3, entry 2). Further experiments
The assignment of each resonance in the 13C NMR spectrum
of 3a as well as the connectivities of the individual 1H spin
systems has been carried out by gHSQC and gHMBC (Fig. 1).
In the HMBC and 13C NMR spectra for compound 3a the proton
6-H is correlated with the quaternary carbon C-4a at δ =
130.69 ppm as well as with the tertiary carbon C-8 at δ =
3
124.28 ppm. The proton 8-H displayed JCH-correlations with
the quaternary carbons C-4a at δ = 130.69 ppm and the quatern-
ary carbon C-1 at δ = 133.0 ppm. The proton 12-H is correlated
with the quaternary carbon C-1 at δ = 133.0 ppm. The proton 4-
3
H exhibited JCH-correlations with the tertiary carbon C-5 at δ =
129.01 ppm and with the quaternary carbon C-9 at δ =
167.39 ppm. These observations and further analysis of the 1D-
and the 2D NMR spectra established the structure of 3a.
This journal is © The Royal Society of Chemistry 2012
Org. Biomol. Chem., 2012, 10, 3899–3905 | 3901

View Article Online
Table 4 The Cu(I)-catalyzed synthesis of naphthalenes 3a–ia,b
Conclusions
In conclusion, a simple to execute and efficient one pot synthesis
of substituted naphthalenes from easily accessible starting
materials has been developed. The Cu(I)-catalyzed reaction of
one molecule of an o-bromobenzaldehyde with two molecules of
a β-ketoester is regarded as a Domino Knoevenagel conden-
sation/C-arylation/1,2-addition/carboxylic acid cleavage process
which delivers the products selectively and with high yields
under mild reaction conditions. o-Iodobenzaldehyde can also be
used as a substrate for this type of annulation.
Entry
1
1
2
Product
Yield (%)
71
Experimental
2
3
4
5
6
7
8
9
73
75
78
73
86
80
81
80
General remarks
All starting materials were purchased from commercial suppliers
(Sigma-Aldrich Chemical Co., Acros Organics, Alfa-Aesar). The
o-bromobenzaldehydes were used without further purification.
All β-ketoesters were freshly distilled over MgSO4 prior to use.
All reactions were carried out under an argon atmosphere in
oven-dried glassware with magnetic stirring. Solvents used in
extraction and purification were distilled prior to use. TLC was
performed on Alugram SIL G/UV254 (Macherey and Nagel).
Compounds were visualized with UV light (λ = 254 nm) and/or
by immersion in ethanolic vanillin solution followed by heating.
Products were purified by flash chromatography on silica gel 60
M, 230–400 mesh (Macherey & Nagel). Melting points were
determined on a Büchi melting point apparatus B-545 with open
capillary tubes and are not corrected. IR spectra were measured
on a Perkin-Elmer Spectrum One FT-IR-spectrometer. UV/VIS
spectra were recorded with a Varian Cary 50. H (13C) NMR
1
spectra were recorded at 300 (75) MHz on a Varian UnityInova
spectrometer using CDCl3 as solvent. The H and 13C chemical
1
shifts were referenced to residual solvent signals at δH/C 7.26/
77.00 (CDCl3) relative to TMS as internal standards. HSQC-,
HMBC- and COSY-spectra were recorded on a Varian UnityInova
at 300 MHz. Coupling constants J [Hz] were directly taken from
the spectra and are not averaged.
a All reactions were performed using 0.5 mmol of 1 and 1.5 mmol of 2
in a sealed vial. b On the TLC traces of a side product with a higher
Rf-value than 3 was observed.
General procedure for the Cu(I)-catalyzed synthesis of
naphthalenes 3a–i
An oven dried 10 mL vial was charged successively with 9.5 mg
(0.05 mmol) CuI (99.999%), 18.6 mg (0.15 mmol) 2-picolinic
acid (99%) (4), 652 mg (2.0 mmol) Cs2CO3 (99.9%), 0.5 mmol
of an o-bromobenzaldehyde 1 and 160 mg molecular sieves
(4 Å). The vial was sealed, evacuated and backfilled with argon
(six times). Then, 1.5 mmol freshly distilled β-ketoester 2 and
3 mL of freshly distilled DMF were added using a syringe. The
reaction mixture was heated in an oil bath at 60 °C for 40 h and
the reaction was monitored by TLC (PE–EtOAc = 5 : 1). After
cooling to room temperature the reaction mixture was partitioned
between 50 mL ethyl acetate and 20 mL brine. The aqueous
phase was extracted with ethyl acetate (2 × 40 mL). The com-
bined organic layers were dried over MgSO4 and concentrated in
vacuo. The residue thus obtained was purified by flash column
chromatography over silica gel (PE–EtOAc = 20 : 1).
Fig. 1 Important HMBC correlations (H → C) of 3a (blue arrow: 2J;
red arrows: 3J).
3902 | Org. Biomol. Chem., 2012, 10, 3899–3905
This journal is © The Royal Society of Chemistry 2012

View Article Online
198 (72), 169 (15), 139 (28) [C11H7]+, 128 (10), 98 (10); HRMS
(EI, M+) calculated for C15H14O4: 258.0892; found: 258.0900.
Spectral data for naphthalenes 3a–i
Diethyl-2-methylnaphthalene-1,3-dicarboxylate
(3a). (a)
According to the general procedure, 92.5 mg (0.5 mmol) o-bro-
mobenzaldehyde (1a) and 195 mg (1.5 mmol) ethyl acetoacetate
(2a) were reacted to afford 102 mg (71%) diethyl-2-methylnaph-
thalene-1,3-dicarboxylate (3a) after column chromatography as a
colourless oil. (b) According to the general procedure 116.0 mg
(0.5 mmol) o-iodobenzaldehyde (1b) and 195 mg (1.5 mmol)
ethyl acetoacetate (2a) were reacted to afford 104 mg (73%)
diethyl-2-methylnaphthalene-1,3-dicarboxylate (3a) after column
chromatography as a colourless oil. Rf = 0.43 (PE–EtOAc =
5 : 1); IR (ATR): ν˜ = 3100 (w; CH2, CH3), 1708 (s; CvO), 1379
(m; alkane C–H), 1297 (m; ester C–O), 1226 (s; ester C–O),
1046 (s), 1012 (m), 960 (m), 895 (m; arom. C–H), 850 (m;
arom. C–H), 784 (s), 752 (s; alkane C–H), 735 cm−1 (w); UV/
Vis (CH3CN): λmax (log ε) = 233 (4.69), 282 (3.66), 335 nm
Diallyl-2-methylnaphthalene-1,3-dicarboxylate (3c). Accord-
ing to the general procedure, 92.5 mg (0.5 mmol) o-bromoben-
zaldehyde (1a) and 213 mg (1.5 mmol) allyl acetoacetate (2c)
were reacted to afford 117 mg (75%) diallyl-2-methylnaphtha-
lene-1,3-dicarboxylate (3c) after column chromatography as a
colourless oil. Rf = 0.40 (PE–EtOAc = 5 : 1); IR (ATR): ν˜ =
2943 (w; CH2, CH3), 1716 (s; CvO), 1467 (m), 1438 (m), 1392
(w; alkane C–H), 1297 (m; ester C–O), 1228 (s; ester C–O),
1213 (s; ester C–O), 1046 (m), 1067 (m), 1045 (m), 991 (s), 938
(s; arom. C–H), 919 (s; arom. C–H) (s), 783 (s), 749 (s; alkane
C–H) (s), 730 cm−1 (m); UV/Vis (CH3CN): λmax (log ε) = 235
(4.75), 282 (3.72), 334 nm (2.62); 1H NMR (300 MHz, CDCl3):
δ = 2.67 (s, 3H; 13-H3), 4.87 (ddd, 2J (10-H, 10-H) = 1.6 Hz, 3J
4
(10-H, 11-H) = 5.7 Hz, J (10-H, 12-H) = 1.3 Hz, 2H; 10-H2),
1
3
(2.58); H NMR (300 MHz, CDCl3): δ = 1.44 (t, J (10-H, 11-
2
3
4.98 (ddd, J (15-H, 15-H) = 1.6 Hz, J (15-H, 16-H) = 6.0 Hz,
H) = 6.9 Hz, 3H; 11-H3), 1.46 (t, 3J (14-H, 15-H) = 6.9 Hz, 3H;
4J (15-H, 17-H) = 1.2 Hz, 2H; 15-H2), 5.33 (ddt, 2J (12a-H,
3
15-H3), 2.67 (s, 3H; 12-H3), 4.42 (q, J (10-H, 11-H) = 7.1 Hz,
3
4
12b-H) = 1.4 Hz, Jcis (11-H, 12b-H) = 10.4 Hz, J (10-H, 12b-
H) = 1.4 Hz, 1H; 12b-H), 5.35 (ddt, 2J (17a-H, 17b-H) = 1.4 Hz,
2H; 10-H2), 4.55 (q, 3J (14-H, 15-H) = 7.2 Hz, 2H; 14-H2), 7.50
(ddd, 3J (6-H, 7-H) = 6.8 Hz, 3J (5-H, 6-H) = 7.9 Hz, 4J (6-H, 8-
H) = 1.2 Hz, 1H; 6-H), 7.60 (ddd, 3J (6-H, 7-H) = 6.9 Hz, 3J (7-
3Jcis (16-H, 17b-H) = 10.7 Hz, J (15-H, 17b-H) = 1.2 Hz, 1H;
4
2
3
17b-H), 5.45 (ddt, J (12a-H, 12b-H) = 1.4 Hz, Jtrans (11-H,
12a-H) = 17.4 Hz, J (10-H, 12a-H) = 1.4 Hz, 1H; 12a-H), 5.47
4
3
H, 8-H) = 6.9 Hz, J (5-H, 7-H) = 1.4 Hz, 1H; 7-H), 7.72 (d, J
4
3
(7-H, 8-H) = 6.9 Hz, 1H; 8-H), 7.89 (br d, J (5-H, 6-H) = 8.3
2
3
(ddt, J (17a-H, 17b-H) = 1.4 Hz, Jtrans (16-H, 17a-H) = 17.2
Hz, 1H; 5-H), 8.45 (s, 1H; 4-H); 13C NMR (75 MHz, CDCl3): δ
= 14.33 (C-11 and C-15), 18.43 (C-12), 61.2 (C-10), 61.6
(C-14), 124.28 (C-8), 126.28 (C-6), 129.0 (C-3), 129.01 (C-5),
129.04 (C-7), 130.69 (C-4a), 131.10 (C-8a), 132.05 (C-2),
132.63 (C-4), 133.0 (C-1), 167.39 (C-9), 169.59 ppm (C-13);
MS (EI, 70 eV): m/z (%) = 287 (14) [M + 1]+, 286 (100) [M+],
257 (14) [C16H17O3]+, 241 [C16H17O2]+, 229 (32) [C15H17O2]+,
212 (63) [C15H16O]+, 184 (24) [C14H16]+, 139 (22) [C11H7]+,
115 [C9H5]+; HRMS (EI, M+) calculated for C17H18O4:
286.1205; found: 286.1177.
Hz, 4J (15-H, 17a-H) = 1.4 Hz, 1H; 17a-H), 6.06 (m, 1H; 11-H),
3
3
6.11 (m, 1H; 16-H), 7.51 (ddd, J (6-H, 7-H) = 6.9 Hz, J (5-H,
4
3
6-H) = 7.7 Hz, J (6-H, 8-H) = 1.3 Hz, 1H; 6-H), 7.60 (ddd, J
(6-H, 7-H) = 6.9 Hz, 3J (7-H, 8-H) = 8.4 Hz, 4J (5-H, 7-H) = 1.5
Hz, 1H; 7-H), 7.73 (br d, 3J (7-H, 8-H) = 8.1 Hz, 1H; 8-H), 7.90
(br d, J (5-H, 6-H) = 8.1 Hz, 1H; 5-H), 8.50 (s, 1H; 4-H); 13C
3
NMR (75 MHz, CDCl3): δ = 18.55 (C-13), 65.85 (C-10), 66.21
(C-15), 118.67 (C-12), 119.65 (C-17), 124.31 (C-8), 126.36
(C-6), 128.51 (C-3), 129.1 (C-5), 129.18 (C-7), 130.67 (C-4a),
131.22 (C-8a), 131.56 (C-16), 132.08 (C-11), 132.35 (C-2),
132.73 (C-1), 132.98 (C-4), 166.88 (C-9), 169.21 ppm (C-14);
MS (EI, 70 eV): m/z (%) = 311 (7) [M + 1]+, 310 (36) [M+], 269
(52) [C16H13O4]+, 253 (64) [C16H13O3]+, 227 (84) [C14H11O3]+,
211 (72) [C14H11O2]+, 181 (64) [C13H9O]+, 139 (100) [C11H7]+,
115 (24) [C9H7]+; HRMS (EI, M+) calculated for C19H18O4:
310.1206; found: 310.1197.
Dimethyl-2-methylnaphthalene-1,3-dicarboxylate
(3b).
According to the general procedure, 92.5 mg (0.5 mmol) o-bro-
mobenzaldehyde (1a) and 174 mg (1.5 mmol) methyl acetoace-
tate (2b) were reacted to afford 94 mg (73%) dimethyl-2-
methylnaphthalene-1,3-dicarboxylate (3b) after column chrom-
atography as a colourless oil. Rf = 0.49 (PE–EtOAc = 5 : 1); IR
(ATR): ν˜ = 3100 (w; CH3), 1712 (s; CvO), 1381 (m; alkane C–
H), 1297 (m; ester C–O), 1240 (s; ester C–O), 1046 (s), 965 (m),
878 (m; arom. C–H), 855 (m; arom. C–H), 763 (s), 751 (s;
alkane C–H), 735 cm−1 (w); UV/Vis (CH3CN): λmax (log ε) =
Dibenzyl-2-methylnaphthalene-1,3-dicarboxylate
(3d).
According to the general procedure, 92.5 mg (0.5 mmol) o-bro-
mobenzaldehyde (1a) and 288 mg (1.5 mmol) benzyl acetoace-
tate (2d) were reacted to afford 160 mg (78%) dibenzyl-2-
methylnaphthalene-1,3-dicarboxylate (3d) after column chrom-
atography as a colourless oil. Rf = 0.41 (PE–EtOAc = 5 : 1); IR
(ATR): ν˜ = 3031 (w; CH2, CH3), 2955 (w; CH2, CH3), 1712 (s;
CvO), 1497 (m), 1455 (m), 1358 (m; alkane C–H), 1296 (m;
ester C–O), 1196 (s; ester C–O), 1139 (s; ester C–O), 1062 (m),
1042 (m), 1027 (m), 973 (m; arom. C–H), 909 (m; arom. C–H),
789 (m), 747 (s; alkane C–H), 696 cm−1 (s); UV/Vis (CH3CN):
1
234 (4.47), 282 nm (3.47); H NMR (300 MHz, CDCl3): δ =
2.66 (s, 3H; 11-H3), 3.96 (s, 3H; 10-H3), 4.06 (s, 3H; 13-H3),
7.54 (ddd, 3J (6-H, 7-H) = 6.9 Hz, 3J (5-H, 6-H) = 8.0 Hz, 4J (6-
3
H, 8-H) = 1.2 Hz, 1H; 6-H), 7.64 (ddd, J (6-H, 7-H) = 7.0 Hz,
4
3J (7-H, 8-H) = 7.1 Hz, J (5-H, 7-H) = 1.4 Hz, 1H; 7-H), 7.73
(d, 3J (7-H, 8-H) = 6.9 Hz, 1H; 8-H), 7.89 (br d, 3J (5-H, 6-H) =
8.3 Hz, 1H; 5-H), 8.48 (s, 1H; 4-H); 13C NMR (75 MHz,
CDCl3): δ = 18.57 (C-11), 52.23 (C-10), 52.48 (C-13), 124.34
(C-8), 126.37 (C-6), 128.47 (C-3), 129.08 (C-5), 129.17 (C-7),
130.66 (C-4a), 131.20 (C-8a), 132.37 (C-2), 132.84 (C-4),
133.01 (C-1), 167.70 (C-9), 170.04 ppm (C-12); MS (EI, 70
eV): m/z (%) = 259 (14) [M + 1]+, 258 (100) [M+], 257 (14)
[M − 1]+, 243 (14) [M − CH3]+, 227 (78) [M − CO]+, 211 (10),
1
λmax (log ε) = 235 nm (4.32); H NMR (300 MHz, CDCl3): δ =
2.63 (s, 3H; 17-H3), 5.40 (s, 2H; 10-H2), 5.52 (s, 2H; 19-H2),
7.47 (overlapped, 1H; 6-H), 7.50–7.53 (overlapped, 10H; 12-H,
12′-H, 13-H, 13′-H, 14-H, 14′-H, 15-H, 15′-H, 16-H and 16′-H),
7.54 (ddd, 3J (6-H, 7-H) = 6.9 Hz, 3J (7-H, 8-H) = 8.5 Hz, 4J (5-
3
H, 7-H) = 1.6 Hz, 1H; 7-H), 7.64 (br d, J (7-H, 8-H) = 8.4 Hz,
This journal is © The Royal Society of Chemistry 2012
Org. Biomol. Chem., 2012, 10, 3899–3905 | 3903

View Article Online
3
3
1H; 8-H), 7.87 (br d, J (5-H, 6-H) = 8.4 Hz, 1H; 5-H), 8.49 (s,
H, 11-H) = 7.1 Hz, 2H; 10-H2), 4.57 (q, J (14-H, 15-H) = 7.2
1H; 4-H); 13C NMR (75 MHz, CDCl3): δ = 18.56 (C-17), 66.97
(C-10), 67.41 (C-19), 124.26 (C-8), 126.32 (C-6), 128.33 (C-12
and C-16), [128.35, 128.40, 128.42, 128.56, 128.66 (overlapped,
C-3, C-13, C-13′, C-14, C-14′, C-15, C-15′)], 128.71 (C-12′ and
C-16′), 129.09 (C-5), 129.16 (C-7), 130.62 (C-4a), 131.23
(C-8a), 132.39 (C-1), 132.69 (C-2), 133.04 (C-4), 135.29
(C-11′), 135.85 (C-11), 167.01 (C-9), 169.34 ppm (C-18); MS
(EI, 70 eV): m/z (%) = 411 (6) [M + 1]+, 410 (22) [M+], 319
(78) [M − C7H7]+, 310 (57) [C20H13O3]+, 283 (13) [C20H11O2]+,
229 (6), 139 (8) [C11H7]+, 91 (100) [C7H7]+; HRMS (EI, M+)
calculated for C27H22O4: 410.1519; found: 410.1541.
Hz, 2H; 14-H2), 7.33 (dd, J (5-H, 6-H) = 7.9 Hz, J (6-H, 8-H)
= 1.3 Hz, 1H; 6-H), 7.46 (s, 1H; 8-H), 7.75 (d, J (5-H, 6-H) =
3
4
3
7.9 Hz, 1H; 5-H), 8.42 (s, 1H; 4-H); 13C NMR (75 MHz,
CDCl3): δ = 14.33 (C-11 and C-15), 18.48 (C-12), 22.2 (C-16),
61.1 (C-10), 61.5 (C-14), 123.28 (C-7), 127.9 (C-8), 128.6
(C-5), 128.9 (C-6), 129.0 (C-3), 131.34 (C-4a), 132.1 (C-8a),
132.4 (C-2), 132.5 (C-4), 139.3 (C-1), 167.46 (C-9), 169.8 ppm
(C-13); MS (EI, 70 eV): m/z (%) = 301 (18) [M + 1]+, 300 (98)
[M+], 286 (4) [C17H18O4]+, 271 (11) [C16H15O4]+, 255 (95)
[C17H19O2]+, 253 (42) [C16H13O3]+, 226 (100) [C15H17O2]+,
198 (42), 153 (16), 115 (7) [C9H5]+; HRMS (EI, M+) calculated
for C18H20O4: 300.1362; found: 300.1383.
Diethyl-6-fluoro-2-methylnaphthalene-1,3-dicarboxylate (3e).
According to the general procedure, 101 mg (0.5 mmol) 2-
bromo-5-fluorobenzaldehyde (1d) and 195 mg (1.5 mmol) ethyl
acetoacetate (2a) were reacted to afford 112 mg (73%) diethyl-6-
fluoro-2-methylnaphthalene-1,3-dicarboxylate (3e) after column
chromatography as a colourless oil. Rf = 0.45 (PE–EtOAc =
5 : 1); IR (ATR): ν˜ = 2979 (w; CH2, CH3), 1728 (s; CvO), 1713
(s; CvO), 1507 (m), 1479 (m), 1452 (s), 1383 (m; alkane C–H),
1326 (m; alkane C–H), 1282 (m; ester C–O), 1207 (s; ester C–
O), 1153 (m), 1129 (m), 1071 (m), 1045 (s), 1013 (m), 914 (m;
arom. C–H), 854 (m; arom. C–H), 828 (m), 779 (w; alkane
C–H), 769 cm−1 (w; alkane C–H); UV/Vis (CH3CN): λmax (log
ε) = 238 (4.68), 231 (4.68), 277 (3.78), 328 nm (3.05); 1H NMR
Diethyl-2-methyl-6,7-methylenedioxy-naphthalene-1,3-dicar-
boxylate (3g). According to the general procedure, 114 mg
(0.5 mmol) 2-bromo-4,5-methylenedioxybenzaldehyde (1f) and
195 mg (1.5 mmol) ethyl acetoacetate (2a) were reacted to
afford 133 mg (80%) diethyl-2-methyl-6,7-methylenedioxy-
naphthalene-1,3-dicarboxylate (3g) after column chromatography
as a colourless oil. Rf = 0.42 (PE–EtOAc = 5 : 1); IR (ATR): ν˜ =
2963 (w; CH2, CH3), 2906 (w; CH2, CH3), 1704 (s; CvO),
1490 (m), 1458 (m), 1366 (w; alkane C–H), 1243 (s; ester C–
O), 1204 (s; ester C–O), 1076 (m), 1035 (s), 943 (m; arom. C–
H), 925 (m; arom. C–H), 803 (s; alkane C–H), 696 cm−1 (s);
1
UV/Vis (CH3CN): λmax (log ε) = 290 (3.82), 331 nm (3.07); H
3
(300 MHz, CDCl3): δ = 1.44 (t, J (10-H, 11-H) = 7.2 Hz, 3H;
NMR (300 MHz, CDCl3): δ = 1.43 (t, 3J (10-H, 11-H) = 7.1 Hz,
3
3
11-H3), 1.46 (t, J (14-H, 15-H) = 7.2 Hz, 3H; 15-H3), 2.64 (s,
3H; 11-H3), 1.44 (t, J (14-H, 15-H) = 7.0 Hz, 3H; 15-H3), 2.61
3H; 12-H3), 4.43 (q, 3J (10-H, 11-H) = 7.4 Hz, 2H; 10-H2), 4.55
(q, 3J (14-H, 15-H) = 7.4 Hz, 2H; 14-H2), 7.36 (ddd, 3J (7-H, 8-
H) = 9.3 Hz, 3J (6-F, 7-H) = 8.3 Hz, 4J (5-H, 7-H) = 2.5 Hz, 1H;
(s, 3H; 12-H3), 4.39 (q, J (10-H, 11-H) = 7.1 Hz, 2H; 10-H2),
3
3
4.52 (q, J (14-H, 15-H) = 7.1 Hz, 2H; 14-H2), 6.07 (s, 2H; 16-
H2), 7.01 (s, 1H; 8-H), 7.14 (s, 1H; 5-H), 8.27 (s, 1H; 4-H); 13C
NMR (75 MHz, CDCl3): δ = 14.33 (C-11 and C-15), 18.32
(C-12), 61.03 (C-10), 61.59 (C-14), 100.9 (C-8), 101.58 (C-16),
104.68 (C-5), 127.19 (C-3), 127.91 (C-4a), 128.89 (C-8a),
130.99 (C-2), 131.47 (C-4), 132.39 (C-1), 147.81 (C-6), 150.29
(C-7), 167.44 (C-9), 169.77 ppm (C-13); MS (EI, 70 eV): m/z
(%) = 331 (16) [M + 1]+, 330 (88) [M+], 301 (7) [M − Et]+, 285
(62) [C16H13O5]+, 273 (82) [C15H13O5]+, 256 (100)
[C15H12O4]+, 228 (44) [C14H12O3]+, 199 (20) [C13H11O2]+, 184
(30) [C12H8O2]+, 171 (11), 143 (10), 126 (22), 115 (24)
[C9H7]+, 77 (10) [C6H5]+; HRMS (EI, M+) calculated for
C18H18O6: 330.1103; found: 330.1092.
3
4
7-H), 7.51 (dd, J (5-H, 6-F) = 9.1 Hz, J (5-H, 7-H) = 2.6 Hz,
3
4
1H; 5-H), 7.73 (dd, J (7-H, 8-H) = 9.4 Hz, J (6-F, 8-H) = 5.5
Hz, 1H; 8-H), 8.36 (s, 1H; 4-H); 13C NMR (75 MHz, CDCl3): δ
= 14.3 (C-11 and C-15), 18.28 (C-12), 61.35 (C-10), 61.74
2
2
(C-14), 112.0 (d, J (C-5, 6-F) = 19.8 Hz, C-5), 119.3 (d, J
3
(C-7, 6-F) = 25.2 Hz, C-7), 126.96 (d, J (C-8, 6-F) = 8.9 Hz,
4
C-8), 128.1 (d, J (C-8a, 6-F) = 1.0 Hz, C-8a), 130.26 (C-3),
131.37 (C-2), 131.51 (C-4a), 131.60 (C-4), 133.1 (br s, C-1),
160.55 (d, J (C-6, 6-F) = 247.9 Hz, C-6), 167.17 (C-9),
169.27 ppm (C-13); MS (EI, 70 eV): m/z (%) = 305 (14) [M +
1]+, 304 (92) [M+], 276 (12) [M − CO]+, 259 (71), 248 (48), 230
(100), 202 (42), 157 (25), 146 (12), 133 (5); HRMS (EI, M+)
calculated for C17H17FO4: 304.1111; found: 304.1109.
Diethyl-2-ethyl-6,7-methylenedioxy-naphthalene-1,3-dicarbox-
ylate (3h). According to the general procedure, 114 mg
(0.5 mmol) 2-bromo-4,5-methylenedioxybenzaldehyde (1f) and
216 mg (1.5 mmol) ethyl propionylacetate (2e) were reacted to
afford 139 mg (81%) diethyl-2-ethyl-6,7-methylenedioxy-
naphthalene-1,3-dicarboxylate (3h) after column chromato-
graphy as a colourless oil. Rf = 0.43 (PE–EtOAc = 5 : 1); IR
(ATR): ν˜ = 2979 (w; CH2, CH3), 2904 (w; CH2, CH3), 1713 (s;
CvO), 1497 (m), 1503 (m), 1479 (s), 1462 (s), 1368 (m; alkane
C–H), 1242 (s; ester C–O), 1196 (s; ester C–O), 1070 (m), 1035
(s), 932 (m; arom. C–H), 861 (m; arom. C–H), 808 (m),
766 cm−1 (w; alkane C–H); UV/Vis (CH3CN): λmax (log ε) =
Diethyl-7-methyl-2-methylnaphthalene-1,3-dicarboxylate (3f).
According to the general procedure, 99.5 mg (0.5 mmol) 2-
bromo-4-methylbenzaldehyde (1e) and 195 mg (1.5 mmol) ethyl
acetoacetate (2a) were reacted to afford 128 mg (86%) diethyl-7-
methyl-2-methylnaphthalene-1,3-dicarboxylate (3f) after column
chromatography as a colourless oil. Rf = 0.44 (PE–EtOAc =
5 : 1); IR (ATR): ν˜ = 2900 (w; CH2, CH3), 2150 (m), 1705 (s;
CvO), 1650 (w), 1440 (m; alkane C–H), 1300 (m; ester C–O),
1235 (s; ester C–O), 1200 (s), 1196 (s), 1180 (s), 1170 (m),
1040 (m), 1031 (s), 813 (m; arom. C–H), 780 cm−1 (s; alkane
C–H); UV/Vis (CH3CN): λmax (log ε) = 242 (4.52), 273 nm
1
248 (4.29), 291 nm (3.73); H NMR (300 MHz, CDCl3): δ =
1
3
(4.47); H NMR (300 MHz, CDCl3): δ = 1.44 (t, J (10-H, 11-
H) = 7.0 Hz, 3H; 11-H3), 1.46 (t, 3J (14-H, 15-H) = 6.9 Hz, 3H;
15-H3), 2.52 (s, 3H; 16-H3), 2.65 (s, 3H; 12-H3), 4.43 (q, 3J (10-
1.26 (t, 3J (12-H, 13-H) = 7.5 Hz, 3H; 13-H3), 1.43 (t, 3J (10-H,
3
11-H) = 7.2 Hz, 3H; 11-H3), 1.45 (t, J (15-H, 16-H) = 7.1 Hz,
3
3H; 16-H3), 3.04 (t, J (12-H, 13-H) = 7.5 Hz, 2H; 12-H2), 4.39
3904 | Org. Biomol. Chem., 2012, 10, 3899–3905
This journal is © The Royal Society of Chemistry 2012

View Article Online
(q, 3J (10-H, 11-H) = 7.1 Hz, 2H; 10-H2), 4.53 (q, 3J (15-H, 16-
H) = 7.1 Hz, 2H; 15-H2), 6.07 (s, 2H; 17-H2), 6.99 (s, 1H; 8-H),
7.14 (s, 1H; 5-H), 8.26 (s, 1H; 4-H); 13C NMR (75 MHz,
CDCl3): δ = 14.29 (C-11 and C-16), 16.10 (C-13), 25.06 (C-12),
61.06 (C-10), 61.55 (C-15), 100.92 (C-8), 101.55 (C-17),
104.62 (C-5), 126.65 (C-3), 127.98 (C-4a), 128.92 (C-8a),
131.84 (C-2), 131.94 (C-4), 136.90 (C-1), 147.85 (C-6), 150.21
(C-7), 167.42 (C-9), 169.72 ppm (C-14); MS (EI, 70 eV): m/z
(%) = 345 (18) [M + 1]+, 344 (100) [M+], 315 (32) [M − Et]+,
299 (38) [C17H15O5]+, 287 (42), 270 (44), 213 (12), 175 (44),
135 (26), 115 (24) [C9H7]+; HRMS (EI, M+) calculated for
C19H20O6: 344.1259; found: 344.1286.
A. W. Thomas, Angew. Chem., Int. Ed., 2003, 42, 5400; (f) K. Kunz,
U. Scholz and D. Ganzer, Synlett, 2003, 2428.
2 (a) A. Padwa, Chem. Soc. Rev., 2009, 38, 3072; (b) D. Enders,
C. Grondal and M. R. M. Hüttl, Angew. Chem., Int. Ed., 2007, 46, 1570;
(c) K. C. Nicolaou, D. J. Edmonds and P. G. Bulger, Angew. Chem., Int.
Ed., 2006, 45, 7134; (d) L. F. Tietze, G. Brasche and K. Gericke, Domino
Reactions in Organic Synthesis, Wiley-VCH, Weinheim, 2006; (e) P.
J. Parsons, C. S. Penkett and A. J. Shell, Chem. Rev., 1996, 96, 195;
(f) L. F. Tietze, Chem. Rev., 1996, 96, 115; (g) L. F. Tietze and
U. Beifuss, Angew. Chem., Int. Ed. Engl., 1993, 32, 131.
3 (a) R. D. Viirre, G. Evindar and R. A. Batey, J. Org. Chem., 2008, 73,
3452; (b) B. Lu, B. Wang, Y. Zhang and D. Ma, J. Org. Chem., 2007, 72,
5337.
4 (a) L. Shi, X. Liu, H. Zhang, Y. Jiang and D. Ma, J. Org. Chem., 2011,
76, 4200; (b) F. Wang, S. Cai, Q. Liao and C. Xi, J. Org. Chem., 2011,
76, 3174; (c) D. Ma, Q. Geng, H. Zhang and Y. Jiang, Angew. Chem., Int.
Ed., 2010, 49, 1291; (d) S. Tanimori, H. Ura and M. Kirihata,
Eur. J. Org. Chem., 2007, 3977.
5 (a) D. Ma, S. Xie, P. Xue, X. Zhang, J. Dong and Y. Jiang, Angew.
Chem., Int. Ed., 2009, 48, 4222; (b) D. Yang, H. Fu, L. Hu, Y. Jiang and
Y. Zhao, J. Org. Chem., 2008, 73, 7841; (c) Q. Yuan and D. Ma, J. Org.
Chem., 2008, 73, 5159; (d) Y. Chen, X. Xie and D. Ma, J. Org. Chem.,
2007, 72, 9329; (e) F. Liu and D. Ma, J. Org. Chem., 2007, 72, 4844;
(f) B. Zou, Q. Yuan and D. Ma, Angew. Chem., Int. Ed., 2007, 46, 2598;
(g) Y. Chen, Y. Wang, Z. Sun and D. Ma, Org. Lett., 2008, 10, 625.
6 (a) W. Xu and H. Fu, J. Org. Chem., 2011, 76, 3846; (b) L. Li, X. Zhang,
Y. Jiang and D. Ma, Org. Lett., 2009, 11, 1309.
7 C. C. Malakar, D. Schmidt, J. Conrad and U. Beifuss, Org. Lett., 2011,
13, 1972.
8 H. Xu, S. Li, H. Liu, H. Fu and Y. Jiang, Chem. Commun., 2010, 46,
7617.
9 For reviews, see: (a) J. E. Anthony, Angew. Chem., Int. Ed., 2008, 47,
452; (b) C. B. de Koning, A. L. Rousseau and W. A. L. van Otterlo,
Tetrahedron, 2003, 59, 7; (c) A. Suzuki, Modern Arene Chemistry, ed. D.
Astruc, Wiley-VCH, Weinheim, 2002; (d) M. D. Watson,
A. Fechtenkötter and K. Müllen, Chem. Rev., 2001, 101, 1267.
10 (a) J. L. Segura and N. Martin, Chem. Rev., 1999, 99, 3199; (b) J.
L. Charlton and M. M. Alauddin, Tetrahedron, 1987, 43, 2873.
11 R. W. Hoffman, Dehydrohenzene and Cycloalkenes, Academic Press,
New York, 1967.
12 R. C. Larock and Q. Tian, J. Org. Chem., 1998, 63, 2002.
13 Q. Huang and R. C. Larock, Org. Lett., 2002, 4, 2505.
14 K. Sakabe, H. Tsurugi, K. Hirano, T. Satoh and M. Miura, Chem.–Eur. J.,
2010, 16, 445.
15 R. Balamurugan and V. Gudla, Org. Lett., 2009, 11, 3116.
16 (a) X. Zhou, Z. Li, H. Wang, M. Kitamura, K.-I. Kanno, K. Nakajima
and T. Takahashi, J. Org. Chem., 2004, 69, 4559; (b) T. Takahashi, Y. Li,
P. Slepnicka, M. Kitamura, Y. Liu, K. Nakajima and M. Kotara, J. Am.
Chem. Soc., 2002, 124, 576; (c) T. Takahashi, R. Hara, Y. Nishihara and
M. Kotora, J. Am. Chem. Soc., 1996, 118, 5154.
17 (a) T. Yasukawa, T. Satoh, M. Miura and M. Nomura, J. Am. Chem. Soc.,
2002, 124, 12680; (b) K. Ueura, T. Satoh and M. Miura, J. Org. Chem.,
2007, 72, 5362.
Dibenzyl-2-methyl-6,7-methylenedioxy-naphthalene-1,3-dicar-
boxylate (3i). According to the general procedure, 114 mg
(0.5 mmol) 2-bromo-4,5-methylenedioxybenzaldehyde (1f) and
288 mg (1.5 mmol) benzyl acetoacetate (2d) were reacted to
afford 183 mg (80%) dibenzyl-2-methyl-6,7-methylenedioxy-
naphthalene-1,3-dicarboxylate (3i) after column chromatography
as a pale yellow solid. M.p. = 151–152 °C; Rf = 0.40 (PE–
EtOAc = 5 : 1); IR (ATR): ν˜ = 1710 (s; CvO), 1497 (m), 1463
(m), 1316 (m; alkane C–H), 1270 (m; ester C–O), 1247 (s; ester
C–O), 1203 (s; ester C–O), 1073 (m), 1032 (s), 938 (m; arom.
C–H), 914 (m; arom. C–H), 849 (m), 753 (s; alkane C–H),
701 cm−1 (s); UV/Vis (CH3CN): λmax (log ε) = 250 (4.54),
1
293 nm (3.70); H NMR (300 MHz, CDCl3): δ = 2.57 (s, 3H;
17-H3), 5.37 (s, 2H; 10-H2), 5.48 (s, 2H; 19-H2), 6.05 (s, 2H;
20-H2), 6.91 (s, 1H; 8-H), 7.11 (s, 1H; 5-H), 7.32–7.50 (over-
lapped, 10H; 12-H, 12′-H, 13-H, 13′-H, 14-H, 14′-H, 15-H, 15′-
H, 16-H and 16′-H), 8.30 (s, 1H; 4-H); 13C NMR (75 MHz,
CDCl3): δ = 18.45 (C-17), 66.82 (C-10), 67.43 (C-19), 100.84
(C-8), 101.59 (C-20), 104.69 (C-5), 126.58 (C-3), 127.85
(C-4a), 128.30 (C-12 and C-16), [128.30, 128.59, 128.68,
128.69 (overlapped, C-13, C-13′, C-14, C-14′, C-15, C-15′,
C-16 and C-16′)], 128.74 (C-12′ and C-16′), 129.09 (C-8a),
131.33 (C-2), 131.84 (C-4), 132.03 (C-1), 135.24 (C-11), 135.97
(C-11′), 147.85 (C-6), 150.41 (C-7), 167.05 (C-9), 169.53 ppm
(C-18); MS (EI, 70 eV): m/z (%) = 455 (3) [M + 1]+, 454 (10)
[M+], 363 (93) [M − C7H7]+, 345 (5) [C21H13O5]+, 327 (2)
[C20H13O4]+, 273 (3), 213 (2), 184 (3), 126 (3), 91 (70)
[C7H7]+; HRMS (EI, M+) calculated for C28H22O6: 454.1428;
found: 454.1433.
18 J.-C. Hsieh and C.-H. Cheng, Chem. Commun., 2008, 2992.
19 W. Huang, X. Zhou, K.-I. Kanno and T. Takahashi, Org. Lett., 2004, 6,
2429.
Acknowledgements
20 (a) E. Yoshikawa, K. V. Radhakrishnan and Y. Yamamoto, J. Am. Chem.
Soc., 2000, 122, 7280; (b) D. Peña, D. Pérez, E. Guitián and L. Castedo,
J. Org. Chem., 2000, 65, 6944; (c) D. Peña, S. Escudero, D. Pérez,
E. Guitián and L. Castedo, Angew. Chem., Int. Ed., 1998, 37, 2659.
21 (a) Y.-T. Wu, K.-H. Huang, C.-C. Shin and T.-C. Wu, Chem.–Eur. J.,
2008, 14, 6697; (b) S. Kawasaki, T. Satoh, M. Miura and M. Nomura, J.
Org. Chem., 2003, 68, 6836; (c) G. Wu, A. L. Rheingold, S. J. Geib and
R. F. Heck, Organometallics, 1987, 6, 1941; (d) T. Sakakibara, Y. Tanaka
and S.-I. Yamasaki, Chem. Lett., 1986, 797.
22 N. Umeda, H. Tsurugi, T. Satoh and M. Miura, Angew. Chem., Int. Ed.,
2008, 47, 4019.
23 (a) A. S. Mayhoub, A. Talukdar and M. Cushman, J. Org. Chem., 2010,
75, 3507; (b) C.-K. Lin and T.-J. Lu, Tetrahedron, 2010, 66, 9688.
We thank Dr. J. Conrad for NMR spectra and Dr. A. Baskakova
for mass spectra.
Notes and references
1 For reviews on Cu-catalyzed C,X- and C,C bond formations,: see:
(a) Y. Liu and J.-P. Wan, Org. Biomol. Chem., 2011, 9, 6873;
(b) F. Monnier and M. Taillefer, Angew. Chem., Int. Ed., 2009, 48, 6954;
(c) G. Evano, N. Blanchard and M. Toumi, Chem. Rev., 2008, 108, 3054;
(d) D. Ma and Q. Cai, Acc. Chem. Res., 2008, 41, 1450; (e) S. V. Ley and
This journal is © The Royal Society of Chemistry 2012
Org. Biomol. Chem., 2012, 10, 3899–3905 | 3905