Synthesis of 2,8-dioxabicyclo[3.3.1]nonane derivatives via a sequential knoevenagel condensation and hetero-Diels-Alder reaction in an aqueous medium

Article abstract of DOI:10.1021/jo401990h

Utilizing aldehyde-substituted vinylogous carbonates and 1,3-diketones, a simple protocol is presented for the synthesis of 2,8-dioxabicyclo[3.3.1]nonane derivatives via Knoevenagel condensation followed by a hetero-Diels-Alder reaction under green reacti

Full text of DOI:10.1021/jo401990h

Note
pubs.acs.org/joc
Synthesis of 2,8-Dioxabicyclo[3.3.1]nonane Derivatives via a
Sequential Knoevenagel Condensation and Hetero-Diels−Alder
Reaction in an Aqueous Medium
Venu Srinivas and Mamoru Koketsu*
Department of Chemistry and Biomolecular Science, Faculty of Engineering, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan
S
* Supporting Information
ABSTRACT: Utilizing aldehyde-substituted vinylogous car-
bonates and 1,3-diketones, a simple protocol is presented for
the synthesis of 2,8-dioxabicyclo[3.3.1]nonane derivatives via
Knoevenagel condensation followed by a hetero-Diels−Alder
reaction under green reaction conditions. The structure of a
key product is unequivocally confirmed by X-ray crystallog-
raphy.
Vinylogous carbonates have been extensively used in organic
synthesis for the construction of many heterocycles and
polycyclics having pharmaceutical and biological significance.
For example, Gharpure and co-workers have been working
extensively on these substrates to achieve the benzoxepines,
oxa-/aza-angular triquinanes, 2,3-disubstituted dihydrobenzo-
furans, oxazino[4,3-a]indoles, unsymmetrical dioxa-cage com-
pounds, 2,3,3,5-tetrasubstituted tetrahydrofurans, and (+)-Ha-
gen’s gland lactones.9,10 On the basis of previous results and
keeping the importance of these vinylogous carbonates in mind,
herein we report a method for the construction of the 2,8-
dioxabicyclo[3.3.1]nonane derivatives by using a gold(III)-
catalyzed reaction of aldehyde-substituted vinylogous carbo-
nates and 1,3-diketones via a domino KC/HDA sequence in an
aqueous medium. Gold catalysts have become a well-
established synthetic tool for the construction of several
heterocycles and polycyclics because simple hydrocarbons
such as alkenes, alkynes, or allenes can be selectively activated
toward the attack of a plethora of carbon- and heteroatom-
based nucleophiles under very mild conditions.11
andem/domino reactions are a powerful tool in organic
Tsynthetic chemistry that allows for efficient and stereo-
selective construction of a plethora of complex molecules from
simple starting materials and combines a variety of trans-
formations in a single reaction vessel.1 These reactions have
been studied in detail by Tietze and co-workers.2 The domino
Knoevenagel and hetero-Diels−Alder reactions of alkene-
substituted aromatic and aliphatic aldehydes with different
1,3-dicarbonyl compounds have been described previously.3 An
important way to reduce human effort, the amount of chemical
waste, and cost is to use tandem reactions, as they involve
multiple sequences of reactions in a single step or one-pot
process.4
The 2,8-dioxabicyclo[3.3.1]nonane motifs have been identi-
fied as attractive synthetic targets because of their prevalence in
many naturally occurring products and due to their medicinally
interesting bioactivities (Chart 1).5 In accordance, a great deal
of effort has been devoted to the synthesis of similar types of
molecular frameworks in recent years.5,6 Recently, this type of
motifs have been synthesized via a silver triflate catalyzed
reaction of 2-hydroxychalcones with naphthols/substituted
phenols6a and an iodine-catalyzed reaction of 2-hydroxychal-
cones with 4-hydroxycoumarines as starting precursors under
environmentally benign conditions.6b A proline-catalyzed
reaction toward these derivatives has also been described;
however, the reaction time was longer (24 h), and more
importantly, the use of acetylacetone and 1,3-cyclopentadione
failed to give the 2,8-dioxabicyclo[3.3.1]nonane derivatives
even at elevated temperatures.6c
The required compounds are aldehyde-based vinylogous
carbonates 1a−e that are prepared from the commercially
available substituted salicyladehydes and ethyl propiolate or
methyl propiolate (Scheme 1).12
At the outset, vinylogous carbonate 1a and the acetylacetone
2a were selected as the model substrates for the AuBr3-
catalyzed Knoevenagel condensation/hetero-Diels−Alder (KC/
HDA) reaction. The diketone 2a was found to be less reactive
when compared to the diketones 2c−d.6c Thus, we chose this
diketone (2a) for the optimization reactions and improvement
of the product yields (Table 1). The reaction of vinylogous
carbonate 1a with diketone 2a in dichloroethane (DCE) as the
solvent at 80 °C in the absence of any catalyst did not produce
the expected product (Table 1, entry 1), and the use of
Organic reactions in aqueous media have attracted much
attention because (i) water induces unique reactivity and
selectivity that are not observed for reactions in organic media
and (ii) water as solvent reduces the use of harmful organic
solvents and may lead to the development of environmentally
friendly chemical processes.7 It is also important to note that
the Diels−Alder reactions can be accelerated in water medium.8
Received: September 10, 2013
Published: October 22, 2013
© 2013 American Chemical Society
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Note
Chart 1. Natural Products Containing 2,8-Dioxabicyclo[3.3.1]nonane Skeleton
AgOTf (10 mol %) or FeCl3(10 mol %) in DCE at 60 °C gave
the product 3a in moderate yield (Table 1, entries 6 and 7).
Fortunately, when the reaction was performed with AuBr3 (5
mol %) in DCE, product 3a was produced in an excellent yield
(Table 1, entry 8). To our surprise, decreasing the catalyst
loading to 1.0 mol % also afforded the product in an excellent
yield (Table 1, entry 9). In our recent studies, we have reported
the propargylamine synthesis by using gold(III) salt as catalyst
in a water medium.11h Therefore, we performed the
Knoevenagel condensation/hetero-Diels−Alder (KC/HDA)
reactions in the aqueous medium, but the yield was very low
(Table 1, entry 10). To our surprise, however, when vinylogous
carbonate 1a was treated with the diketone 2a using catalytic
AuBr3 (1 mol %) in ethanol/water (1:1), compound 3a was
produced in excellent yield (Table 1, entry 11). Changing the
ratio of ethanol/water to 1:4 also provided an excellent yield
(Table 1, entry 12). The reaction time was longer (4 h) when
we used 1.0 molar equiv of the 1,3-diketone, and the yield of
the compound 3a did not change (92%) by decreasing the 1,3-
Scheme 1. Synthesis of Aldehyde-Substituted Vinylogous
Carbonates 1a−e
organocatalyst D-proline in EtOAc as the solvent produced only
5% of the isolated product 3a (Table 1, entry 2). Therefore, we
changed our attention to the metal catalysts. The use of ZnBr2
(20 mol %) in dichloroethane (DCE) at 80 °C failed to give the
product (Table 1, entry 3). With Zn(OTf)2 (10 mol %) as
catalyst in DCE or toluene, product 3a was formed in moderate
yields (Table 1, entries 4 and 5). The use of metal salts like
Table 1. Optimization Studies for the Synthesis of 2,8-Dioxabicyclo[3.3.1]nonane Derivative 3a
entry
catalyst (mol %)
solvent
DCE
temp (°C)
time (h)
yield (%) (3a)
a
1
80
50
24
24
18
18
20
7
NR
2
D-proline
EtOAc
5
a
3
ZnBr2 (20)
Zn(OTf)2 (10)
Zn(OTf)2 (10)
AgOTf (10)
FeCl3 (10)
AuBr3 (5)
DCE
80
NR
4
DCE
60
58
43
62
36
89
85
10
95
92
43
5
toluene
100
60
6
DCE
7
DCE
80
6
8
DCE
50
8
9
AuBr3 (1)
DCE
50
8
10
11
12
13
14
15
16
17
18
19
AuBr3 (1)
H2O
60
10
4
AuBr3 (1)
EtOH/H2O (1:1)
EtOH/H2O (1:4)
EtOH/H2O (1:1)
EtOH/H2O (1:1)
EtOH/H2O (1:1)
DMF
60
AuBr3 (1)
60
2
Zn(OTf)2 (10)
FeCl3 (10)
CuI (10)
80
16
18
20
18
14
20
16
a
80
NR
a
80
NR
AuBr3 (5)
100
100
60
50
64
42
54
AuBr3 (5)
toluene
AuBr3 (5)
THF
AuBr3 (5)
acetonitrile
80
a
NR = no reaction.
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Note
Table 2. Substrate Scope of the Synthesis of 2,8-Dioxabicyclo[3.3.1]nonane Derivatives 3a−m
a
Reaction conditions: compound 1 (0.23 mmol) and compound 2 (0.46 mmol) in ethanol/water (1:4, 4 mL) and AuBr3 (1.0 mg, 0.0023 mmol) at
60 °C for 2−3 h.
diketone molar equivalents. Thus, we believe that the reaction
can be performed by using green conditions that can reduce the
chemical waste. However, except for Zn(OTf)2, the use of
other metal salts like FeCl3 and CuI did not produce the KC/
HDA product (Table 1, entries 13−15). We have also studied
the solvent effect by using AuBr3 (5 mol %) as the catalyst.
When the reaction was carried out by changing the solvents,
such as DMF, toluene, THF, and acetonitrile, the product 3a
was obtained in moderate yields (Table 1, entries 16−19).
With the optimal reaction conditions in hand, we then
examined the KC/HDA reaction of various aldehyde-based
vinylogous carbonates 1a−e and 1,3-diketones 2a−d in
aqueous medium to afford the bicyclic compounds (3) in
good yields (Table 2). The incorporation of the gold(III)
catalyst increased the yield, and the reaction was completed in a
short reaction time (2−3 h) when compared to the proline-
catalyzed conditions. By using the optimized conditions, the
vinylogous carbonates 1a,b were treated with acetylacetone
(2a) to yield the products 3a,b in excellent yields (92% and
88%, entries 1 and 2, Table 2). These compounds are
1
characterized by their H/13C NMR spectra. The product 3b
was further confirmed by single-crystal X-ray crystallography
(see the Supporting Information, Figure S1). It is interesting to
note that the reaction of bromine-substituted vinylogous
carbonate 1b with the less reactive 1,3-cyclopantadione 2b
also afforded the product 3c in good yield (79%, Table 2). The
bromine-substituted and methoxy-substituted vinylogous car-
bonates 1b,c also reacted smoothly with the diketones 2c,d to
yield the final products 3d−i. The reaction mixture contained
exclusively the final product, and it could be easily passed
through a short silica gel column to afford the expected product
in excellent isolated yields (90−98%, entries 4−9, Table 2).
The different types of vinylogous carbonates 1d−e were also
employed as the starting materials to establish the generality of
the present transformation. When compound 1d was treated
with acetylacetone (2a), it was interesting to note that the
reaction successfully yielded the expected product 3j in high
yield (95%, entry 10, Table 2). In a similar manner, the reaction
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Note
Scheme 2. Possible Pathway for the Formation of Compound 3a via KC/HDA Reaction
diluted with ethyl acetate (10 mL), and an excess of water (5 mL) and
extracted. The aqueous layer was washed again with ethyl acetate (10
mL). The combined organic layer was washed with water (10 mL) and
saturated brine solution (10 mL) and dried over anhydrous Na2SO4.
Subsequent evaporation of organic solvent by using a rotary
evaporator afforded a brown gummy material. The residue was
purified by silica gel column chromatography [hexanes/ethyl acetate
(1:4)] to give the final compound 3a.
of bromine-substituted compound 1e with 1,3-cyclopentadione
(2b) also furnished the product 3k in excellent yields (86%,
entry 11, Table 2). Finally, reaction of the compound 1e with
1,3-diketones 2c,d was also gave the expected products 3l,m in
very good yields (96% and 90%, entries 12 and 13, Table 2).
Overall, these results highlight the great potential and versatility
of the method, which provides a direct and practical access to
highly valuable 2,8-dioxabicyclo[3.3.1]nonane derivatives from
readily accessible starting materials.
The remaining products (3b−m) were also prepared by following
the general procedure using the same molar quantities of 1a−e and
2a−d.
On the basis of a previous report,13 the present Au(III)-
catalyzed domino process can be rationalized as depicted in
Scheme 2. Initially, the intermediate A was formed via
Knoevenagel condensation, and then this intermediate A
underwent hetero-Diels−Alder reaction in [4 + 2] fashion to
form only one diastereomer (3a). It may be due to the
restricted conformation of intermediate A, as revealed from the
X-ray crystal structure of final product 3b (Figure S1,
Supporting Information).
Compound 3a: yield 0.066 g (92%); gummy liquid; IR (CHCl3,
1
cm−1) 2951, 1739, 1631, 1472, 1386, 1229; H NMR (400 MHz,
CDCl3) δ 1.24 (t, J = 7.3 Hz, 3H), 2.21 (s, 3H), 2.39 (s, 3H), 3.07
(dd→t, J = 1.3 Hz, 1H), 4.13−4.26 (m, 2H), 4.60 (br, 1H), 6.24 (t, J =
1.8 Hz, 1H), 6.88−6.95 (m, 2H), 7.11−7.16 (m, 1H), 7.30−7.33 (m,
1H); 13C NMR (100 MHz, CDCl3) δ 14.2, 20.5, 28.9, 30.9, 40.1, 61.5,
91.5, 116.5, 121.9, 125.4, 128.2, 128.3, 150.1, 162.2, 168.4, 196.0; MS
(EI) m/z 302 [M]+. Anal. Calcd for C17H18O5: C, 67.54; H, 6.00.
Found: C, 67.41; H, 5.73.
Compound 3b: yield 0.076 g (88%); mp 152−154 °C; IR (CHCl3,
In summary, we have described an effective AuBr3-catalyzed
protocol for the synthesis of 2,8-dioxabicyclo[3.3.1]nonane
derivatives via the domino Knoevenagel condensation/hetero-
Diels−Alder reaction in an aqueous reaction medium. The
precursors used are aldehyde-based vinylogous carbonates and
1,3-diketones. We have also shown that the less reactive 1,3-
diketones such as acetylacetone and 1,3-dicyclopentadione are
effective under the reaction conditions to provide 2,8-
dioxabicyclo[3.3.1]nonane derivatives. The products are
important motifs in many natural products and pharmaceut-
icals, and this atom-economical and mild approach delivers an
attractive alternative to the classical protocols.
1
cm−1) 2952, 1740, 1632, 1472, 1386, 1228; H NMR (400 MHz,
CDCl3) δ 1.24 (t, J = 7.2 Hz, 3H), 2.22 (s, 3H), 2.39 (s, 3H), 3.03
(dd→t, J = 1.4 Hz, 1H), 4.12−4.26 (m, 2H), 4.59 (br, 1H), 6.24 (t, J =
1.8 Hz, 1H), 6.80 (d, J = 8.7 Hz, 1H), 7.23 (dd, J = 8.7, 2.2 Hz, 1H),
7.46 (d, J = 2.2 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 14.2, 20.6,
28.5, 31.0, 39.8, 61.6, 91.4, 114.2, 116.4, 118.3, 127.6, 130.9, 131.2,
149.4, 162.4, 168.0, 195.5; MS (EI) m/z 380 [M]+. Anal. Calcd for
C17H17BrO5: C, 53.56; H, 4.50. Found: C, 53.23; H, 4.64. This
compound was crystallized from ethyl acetate/hexane (1:9, 2 mL)
mixture at 20 °C. The X-ray structure was determined for this sample
(Figure S1, Supporting Information).
Compound 3c: yield 0.068 g (79%); mp 157−159 °C; IR (CHCl3,
1
cm−1) 2952, 1741, 1634, 1472, 1385, 1286; H NMR (400 MHz,
CDCl3) δ 1.25 (t, J = 7.4 Hz, 3H), 2.40−2.45 (m, 2H), 2.53−2.57 (m,
2H), 3.13 (dd→t, J = 2.3 Hz, 1H), 4.16−4.24 (m, 3H), 6.42 (t, J = 1.8
Hz, 1H), 6.82 (d, J = 8.7 Hz, 1H), 7.22−7.26 (m, 1H), 7.43 (t, J = 2.3
Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 14.2, 25.8, 26.3, 34.3, 40.3,
61.9, 94.2, 114.6, 118.3, 118.7, 126.9, 130.6, 131.4, 149.8, 167.4, 181.2,
200.5; MS (EI) m/z 378 [M]+. Anal. Calcd for C17H15BrO5: C, 53.85;
H, 3.99. Found: C, 53.85; H, 4.17.
EXPERIMENTAL SECTION
■
General Remarks. All materials were obtained and used as
received from commercial sources unless otherwise noted. Melting
points were recorded on a micromelting point apparatus. Infrared (IR)
spectra were recorded on a FT/IR (Fourier transform infrared
1
spectrometer) in CHCl3. H NMR (400 MHz) and 13C NMR (100.6
Compound 3d: yield 0.077 g (98%); mp 163−165 °C; IR (CHCl3,
MHz) spectra were determined at rt on a 400 MHz spectrometer in
CDCl3 solution. Chemical shifts are expressed in parts per million
(ppm) downfield from tetramethylsilane for 1H spectra and are
referenced to CDCl3 for 13C (δC 77.16). Data are reported as follows:
chemical shift, multiplicity (s = singlet, d = doublet, t = triplet, dd =
doublet of doublet, q = quartet and m = multiplet), coupling constants
(Hz), and integration. The mass spectra (MS) were measured on a
mass spectrometer (EI). Analytical thin-layer chromatography (TLC)
was performed on a silica gel glass plate. Silica gel 60N (spherical,
neutral) was received by local manufacturer and used for flash column
chromatography, and the column was usually eluted with ethyl
acetate−hexane mixture. The starting materials 1a−e are prepared by
1
cm−1) 2966, 1734, 1631, 1462, 1387, 1234; H NMR (400 MHz,
CDCl3) δ 0.94 (s, 3H), 0.99 (s, 3H), 1.25 (t, J = 7.2 Hz, 3H), 2.16−
2.32 (m, 4H), 3.11 (dd→t, J = 2.8 Hz, 1H), 4.12−4.24 (m, 2H), 4.54
(br, 1H), 6.30 (t, J = 4.1 Hz, 1H), 6.86−6.92 (m, 2H), 7.09−7.13 (m,
1H), 7.34 (dd, J = 7.8, 2.0 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ
14.2, 25.4, 27.1, 29.3, 32.5, 40.2, 41.2, 50.3, 61.6, 92.3, 114.0, 116.1,
122.0, 125.5, 128.0, 128.4, 150.2, 166.8, 168.3, 195.4; MS (EI) m/z
342 [M]+. Anal. Calcd for C20H22O5: C, 70.16; H, 6.48. Found: C,
70.48; H, 6.14.
Compound 3e: yield 0.092 g (96%); mp 122−124 °C; IR (CHCl3,
1
cm−1) 2960, 1736, 1636, 1471, 1385, 1233; H NMR (400 MHz,
following the reported procedures, and the H/13C NMR data are
1
CDCl3) δ 0.97 (s, 3H), 0.99 (s, 3H), 1.25 (t, J = 7.2 Hz, 3H), 2.19−
2.34 (m, 4H), 3.07 (dd→t, J = 2.7 Hz, 1H), 4.11−4.22 (m, 2H), 4.50
(br, 1H), 6.30 (t, J = 2.3 Hz, 1H), 6.80 (d, J = 9.2 Hz, 1H), 7.21 (dd, J
= 9.2, 2.3 Hz, 1H), 7.48 (d, J = 2.3 Hz, 1H); 13C NMR (100 MHz,
CDCl3) δ 14.2, 25.2, 27.1, 29.4, 32.6, 40.0, 41.2, 50.3, 61.7, 92.3, 113.5,
114.2, 118.0, 127.5, 130.9, 131.0, 149.5, 166.9, 167.9, 195.2; MS (EI)
m/z 420 [M]+. Anal. Calcd for C20H21BrO5: C, 57.02; H, 5.02. Found:
C, 57.02; H, 5.33.
consistent with the reported compounds.12
General Procedure for the Synthesis of 2,8-Dioxabicyclo-
[3.3.1]nonane Derivative (3a). To a solution of 1a (0.23 mmol)
and 2a (0.46 mmol) in ethanol/water (1:4, 4 mL) was added AuBr3
(1.0 mg, 0.0023 mmol) and the mixture stirred at 60 °C for 2−3 h.
When there was no starting material remaining (TLC or H NMR),
the reaction mixture was concentrated in vacuo. Then the mixture was
1
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Note
Compound 3f: yield 0.077 g (90%); gummy liquid; IR (CHCl3,
1H); 13C NMR (100 MHz, CDCl3) δ 20.6, 25.4, 27.5, 36.4, 40.0, 52.7,
92.0, 114.3, 114.5, 118.0, 127.6, 131.1, 149.5, 168.4, 168.6, 195.5; MS
(EI) m/z 378 [M]+. Anal. Calcd for C17H15BrO5: C, 53.85; H, 3.99.
Found: C, 53.62; H, 3.78.
X-ray Data. Single-crystal X-ray diffraction data for compound 3b
were collected on a X-ray diffractometer with graphite-monochro-
mated Mo Kα radiation (λ = 0.71069 Å). The structure was solved and
refined by standard methods.
Crystal data for compound 3b: colorless plate, C17H17BrO5, M =
381.21, monoclinic, space group C2/c, a = 23.335(6) Å, b =
6.2952(15) Å, c = 23.129(6) Å, β = 107.557(3)°, V = 3239.3(14) Å3, Z
= 8, μ = 2.561 mm−1, data/restraints/parameters: 3724/0/211, R
indices (I > 2σ(I)): R1 = 0.0346, wR2 (all data) = 0.1242. The data
(CCDC no. 957790) can be obtained free of charge from the
Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/
data_request/cif.
1
cm−1) 2958, 1735, 1632, 1383, 1157; H NMR (400 MHz, CDCl3) δ
0.95 (s, 3H), 0.98 (s, 3H), 1.24 (t, J = 7.3 Hz, 3H), 2.16−2.29 (m,
4H), 3.09 (dd→t, J = 1.8 Hz, 1H), 3.73 (s, 3H), 4.17 (q, J = 7.3 Hz,
2H), 4.48 (br, 1H), 6.28 (t, J = 1.8 Hz, 1H), 6.44−6.47 (m, 2H), 7.22
(d, J = 9.0 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 14.2, 24.7, 27.0,
29.2, 32.5, 40.5, 41.1, 50.3, 55.4, 61.5, 92.3, 101.7, 108.0, 114.4, 117.9,
128.8, 151.0, 159.5, 166.5, 168.3, 195.4; MS (EI) m/z 372 [M]+. Anal.
Calcd for C21H24O6: C, 67.73; H, 6.50. Found: C, 67.82; H, 6.45.
Compound 3g: yield 0.068 g (95%); gummy liquid; IR (CHCl3,
1
cm−1) 2928, 1735, 1630, 1459, 1385, 1234; H NMR (400 MHz,
CDCl3) δ 1.23 (t, J = 7.3 Hz, 3H), 1.86−1.92 (m, 2H), 2.24−2.34 (m,
2H), 2.39−2.42 (m, 2H), 3.10 (dd→t, J = 3.2 Hz, 1H), 4.10−4.27 (m,
2H), 4.55 (br, 1H), 6.30 (t, J = 2.3 Hz, 1H), 6.89−6.93 (m, 2H),
7.10−7.15 (m, 1H), 7.36 (dd, J = 8.3, 2.1 Hz, 1H); 13C NMR (100
MHz, CDCl3) δ 14.2, 20.7, 25.5, 27.5, 36.4, 40.3, 61.5, 92.2, 115.1,
116.2, 122.0, 125.5, 128.1, 128.6, 150.2, 168.3, 168.6, 195.7; MS (EI)
m/z 314 [M]+. Anal. Calcd for C18H18O5: C, 68.78; H, 5.77. Found: C,
68.45; H, 5.52.
Compound 3h: yield 0.088 g (98%); mp 136−138 °C; IR (CHCl3,
cm−1) 2948, 1736, 1632, 1472, 1385, 1230, 1174; 1H NMR (400
MHz, CDCl3) δ 1.23 (t, J = 7.3 Hz, 3H), 1.87−1.94 (m, 2H), 2.30−
2.35 (m, 2H), 2.40−2.43 (m, 2H), 3.07 (dd→t, J = 2.8 Hz, 1H), 4.11−
4.26 (m, 2H), 4.51 (br, 1H), 6.28 (t, J = 1.7 Hz, 1H), 6.79 (d, J = 8.7
Hz, 1H), 7.22 (dd, J = 8.7, 2.7 Hz, 1H), 7.49 (d, J = 2.7 Hz, 1H); 13C
NMR (100 MHz, CDCl3) δ 14.2, 20.6, 25.3, 27.4, 36.3, 40.0, 61.6,
92.0, 114.2, 114.5, 118.0, 127.5, 131.00, 131.05, 149.4, 167.8, 168.6,
195.4; MS (EI) m/z 392 [M]+. Anal. Calcd for C18H17BrO5: C, 54.98;
H, 4.36. Found: C, 54.62; H, 4.44.
ASSOCIATED CONTENT
■
S
* Supporting Information
Materials including the ORTEP diagram of the compound 3b,
1
copies of H/13C NMR spectra of all new products, and X-ray
data of compound 3b (CIF). This material is available free of
charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail: koketsu@gifu-u.ac.jp.
■
Notes
Compound 3i: yield 0.072g (92%); mp 182−184 °C; IR (CHCl3,
cm−1) 2948, 1736, 1632, 1472, 1385, 1230, 1174; 1H NMR (400
MHz, CDCl3) δ 1.23 (t, J = 7.3 Hz, 3H), 1.86−1.94 (m, 2H), 2.28−
2.42 (m, 4H), 3.07 (dd→t, J = 2.3 Hz, 1H), 3.74 (s, 3H), 4.12−4.24
(m, 2H), 4.48 (br, 1H), 6.28 (t, J = 1.8 Hz, 1H), 6.46−6.48 (m, 2H),
7.22−7.28 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 14.2, 20.7, 24.9,
27.4, 36.4, 40.6, 55.5, 61.4, 92.1, 101.7, 108.1, 115.5, 117.9, 128.9,
151.0, 159.6, 168.30, 168.32, 195.7; MS (EI) m/z 344 [M]+. Anal.
Calcd for C19H20O6: C, 66.27; H, 5.85. Found: C, 66.19; H, 5.86.
Compound 3j: yield 0.063 g (95%); mp 150−152 °C; IR (CHCl3,
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by The Greater Nagoya Invitation
Program for International Research Scientists in Environmental
Science Field to which we are grateful.
REFERENCES
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1
cm−1) 2951, 1739, 1631, 1472, 1386, 1173; H NMR (400 MHz,
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1
cm−1) 2950, 1731, 1635, 1469, 1228; H NMR (400 MHz, CDCl3) δ
0.97 (s, 3H), 0.98 (s, 3H), 2.19−2.30 (m, 4H), 3.08 (dd→t, J = 2.8
Hz, 1H), 3.71 (s, 3H), 4.50 (br, 1H), 6.30 (t, J = 1.8 Hz, 1H), 6.79 (d,
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