Synthesis of new chiral and racemic 1,3-dioxolanes

Article abstract of DOI:10.1002/jhet.937

A series of chiral 1,3-dioxolanes, 3-12, with >99% ee values, have been synthesized. This is the first study of chiral ketalization reaction starting from ketones with aryl, monosubstituted aryl, and long alkyl chains (C ₁₁-AC₁₃). Their ee values were determined by chiral high-performance liquid chromatography (HPLC) on Chiralcel OD column, using their racemic 1,3-dioxolanes rac-3-12, which were also synthesized for the first time. These chiral and racemic 1,3-dioxolanes were characterizated by infrared, NMR (¹H, ¹³C), mass spectrometry, elemental analysis, optical rotation, and chiral HPLC.

Full text of DOI:10.1002/jhet.937

1066
Synthesis of New Chiral and Racemic 1,3-Dioxolanes
Vol 49
*
Hatice Başpınar Küçük and Ayşe Yusufoğlu
Department of Chemistry, Faculty of Engineering, Istanbul University
34320 Avcılar, Istanbul, Turkey
*
E-mail: ayseserg@istanbul.edu.tr
Additional Supporting Information may be found in the online version of this article.
Received February 3, 2011
DOI 10.1002/jhet.937
Published online 26 October 2012 in Wiley Online Library (wileyonlinelibrary.com).
A series of chiral 1,3-dioxolanes, 3–12, with >99% ee values, have been synthesized. This is the first
study of chiral ketalization reaction starting from ketones with aryl, monosubstituted aryl, and long alkyl
chains (C11—AC13). Their ee values were determined by chiral high-performance liquid chromato-
graphy (HPLC) on Chiralcel OD column, using their racemic 1,3-dioxolanes rac-3–12, which were also
synthesized for the first time. These chiral and racemic 1,3-dioxolanes were characterizated by infrared,
NMR (1H, 13C), mass spectrometry, elemental analysis, optical rotation, and chiral HPLC.
J. Heterocyclic Chem., 49, 1066 (2012).
INTRODUCTION
using the catalyst Mont.K10, other catalysts such as
p-toluenesulfonic acid and Amberlyst 15 were tried.
Mont.K10 was found to be the best catalyst result-
ing in the formation of 1,3-dioxolanes from ketones
with aryl, monosubstituted aryl, and long alkyl chains
(C11—C13).
According to literature search, Mont.K10 catalyzes the
formation of 1,3-dioxolanes from a various of aldehydes
with ethane-1,2-diol. The sterically hindered ketones,
however, failed to react with diols under same reaction
conditions. Several 1,3-dioxolanes have been prepared
using cyclic and aliphatic ketones with short chain
lengths and benzylic ketones in the presence of Mont.
K10 as an acidic catalyst [6].
However, chiral 1,3-dioxolanes with long alkyl chain
lengths are missing from the literature. Therefore, the aim
of this work was to synthesize chiral 1,3-dioxolanes with
aryl, monosubstituted aryl, and long alkyl chain groups
(C11—C13). Ketones 1a–e with aryl, monosubstituted aryl,
and long alkyl chains (C11—C13) were used for chiral
ketalization reaction applied in this study. The ketones 1d
and 1e are original. (R,R)-Diisopropyl-L-tartrate, (R,R)-
dimethyl-L-tartrate, and montmorillonite K-10 were the
other reagents, and the reaction took place under the condi-
tions described in the experimental part.
Ten different chiral (4R,5R)-1,3-dioxolanes 3–12 were
synthesized as original 1,3-dioxolanes for the first time
in this study (Table 1). Their racemic dioxolane com-
pounds rac-3–12 have not been reported in the literature,
therefore they were obtained as original racemic dioxo-
lanes rac-3–12 by ketalization of the ketones mentioned
Compounds with 1,3-dioxolane’s structure are of
interest in the industry for the preparation of many
pharmaceuticals and fragrances [1]. They are also ap-
preciated as starting chiral pools for the synthesis of
different natural compounds, like in the synthesis of
(R)-muscone, which was synthesized using a chiral
cyclic acetal [2].
1,3-Dioxolane structures have been described as chiral
inhibitors of leukotrienes, which are a family of impor-
tant biological molecules. 2-Acetylnaphtalene deriva-
tives with a dioxolane structure were screened for their
anticonvulsant activities. Similarly, isatin and its deriva-
tives having dioxolane moieties exert pharmacological
effects on the central nervous system, including anxio-
genic, sedative, and anticonvulsant activities. Some
cyclic ketals resulted from a cineole ketone were sub-
mitted to antimicrobial assays and showed their activity
against several microorganisms [3].
The most convenient and practical method for the
preparation of acetals is the reaction of carbonyl com-
pounds with 1,2-diols in the presence of an acid catalyst.
The catalysts commonly used are sulfuric acid, hydro-
cloric acid, phosphoric acid, and p-toluenesulfonic acid.
These catalysts are often corrosive, difficult to work-up,
and are not environmentally friendly [4].
In this study, montmorillonite K10-catalyst was used,
which is of strong acidity and inexpensive, exposing
mild reaction conditions, selectivity, easily set- and
work-up possibility, and giving high yields [5]. Before
© 2012 HeteroCorporation

September 2012
Synthesis of New Chiral and Racemic 1,3-Dioxolanes
1067
Table 1
Table 2
Ketalization of orthoesters with chiral diols (2a,2b) by montmorillonite
Ketalization of orthoesters with racemic diols (2c,2d) by montmorillonite
K10 catalyst.a
K10 catalyst.a
Entry
Ketone
Diol
Product
eeb (%)
Yieldc (%)
(tRR)b
(min)
(tSR)b
(min)
Yieldc
(%)
Entry Ketone Diol
Product
1
2
3
4
5
6
7
8
9
10
1a
1a
1b
1b
1c
1c
1d
1d
1e
1e
2a
2b
2a
2b
2a
2b
2a
2b
2a
2b
3
4
5
6
7
8
9
10
11
12
>99
>99
>99
>99
>99
>99
>99
>99
>99
>99
82
75
80
77
84
75
84
75
68
65
1
2
3
4
5
6
7
8
9
1a
1a
1b
1b
1c
1c
1d
1d
1e
1e
2c
2d
2c
2d
2c
2d
2c
2d
2c
2d
rac-3
rac-4
rac-5
rac-6
rac-7
rac-8
rac-9
rac-10
rac-11
rac-12
4.225
4.210
4.331
4.370
4.160
4.540
5.327
5.650
5.400
5.620
4.965
6.010
6.091
5.270
5.420
6.210
6.377
6.880
6.930
7.320
85
77
82
79
85
77
87
76
70
68
10
aAll reactions were carried out under Dean-Stark conditions.
bThe enantiomeric excesses were determined by HPLC using a Chiralcel
OD column. The separation conditions were given in experimental part.
cIsolated yield.
aAll reactions were carried out under Dean-Stark conditions.
bThe retention times were determined by HPLC using a Chiralcel OD
column. Entries 1–6: mobile phase iso-PrOH/hexane: 5/95. Entries 7–10:
mobile phase iso-PrOH/hexane: 3/97.
cIsolated yield.
above with racemic dimethyl tartrate (2c) and racemic
diisopropyl tartrate (2d), respectively (Table 2). These
10 racemic 1,3-dioxolanes were used for enantiosepera-
tion and %ee analysis by chiral high-performance liquid
chromatography (HPLC) on Chiralcel OD column, which
was made also for the first time.
Chiral dioxolanes 3–12 (Table 1) were obtained by the
reaction of orthoesters with chiral diols (2a,2b) using
Mont.K10 catalyst.
Racemic dioxolanes rac-3–12 (Table 2) were synthe-
sized by the reaction of orthoesters with racemic diols
(2c,2d) in the presence of Mont.K10 catalyst.
RESULTS AND DISCUSSION
CONCLUSIONS
In the first step of our study, five prochiral alkyl phenyl
ketones 1a–e were synthesized via Friedel Crafts reaction
(Scheme 1) [7]. Two of them (1d and 1e) were obtained
for the first time in this study.
Ketalization was more difficult for sterically hindered
ketones 1a–e used in this study. The key step of the asym-
metric ketalization strategy was solved in this study by
adding TMOF. Direct ketalization did not work for long
chain ketone substrates, we discovered that TMOF can
Initial attempts to ketalize ketones 1a–e directly with
diols (2a,2b) had no success. Therefore, these sterically
hindered ketones 1a–e were activated by trimethyl
orthoformate (TMOF) by converting them to their more
reactive orthoesters (Scheme 2). These orthoesters gave,
then, the asymmetric ketalization reaction with chiral
(2a,2b) and racemic diols (2c,2d) successfully with
good yields and high enantiomeric excesses (>99%
ee). In this activated ketalization reaction, methanol
was separated instead of water and easy azeotropic
removal of methanol, formed during the reaction, would
force the equilibrium toward the cyclization products. In
the literature, TMOF has been added only in some cases
as additive [2,8], but the effect of TMOF has not been
explained. This work demonstrates the importance of
TMOF for sterically hindered ketones.
Scheme 1. Synthesis of prochiral alkyl phenyl ketones (1a–e).
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

1068
H. B. Küçük and A. Yusufoğlu
Vol 49
Scheme 2. Reaction of ketones with TMOF.
cooling, the catalyst was removed by filtration. The reaction
mixture was washed with solid NaHCO3 and water. The
organic layer was dried (MgSO4) and the solvent was
evaporated under reduced pressure. The colorless oil was
purified by flash chromatography (silica gel, hexane/ethyl
acetate as an eluent) to give 1,3-dioxolane in excellent yield.
Dimethyl (4R,5R)-2-phenyl-2-undecyl-1,3-dioxolane-4,5-dicar-
boxylate (3). Yield 0.344 g (82%), light yellow oil and >99%
ee. [a]2D0 +22 (c 1,CHCl3). IR nmax (neat)/cmÀ1 3060, 2946,
catalyze the reaction and make it work. In this way, the
10 new enantiopure 1,3-dioxolanes 3–12 and the 10
new racemic 1,3-dioxolanes rac-3–12 with long alkyl
chains could be synthesized with high enantiomeric
excesses and yields. The (4R,5R)- and (4S,5S)-enantiomers
of 1,3-dioxolanes has not been resolved before in the
literature, and therefore, racemic 1,3-dioxolanes were
enantioseparated on chiral HPLC. The (S,S)-enantiomers
came later than the (R,R)-enantiomers with changing
retention time values (Table 2).
1
2892, 1754, 1456, 1239, 1104, 1050, 752, 725. H-NMR (400
MHz, CDCl3): d 7.31–7.48 (5H, m), 4.76–4.81 (2H, dd, J =
5.85 Hz), 3.83 (3H, s), 3.53 (3H, s), 1.97 (2H, t, J = 7.3 Hz),
1.22–1.39 (18H, m), 0.87 (3H, t, J = 7.3 Hz). 13C-NMR (125
MHz, CDCl3): d 168.33, 139.93, 127.2, 126.86, 124.96,
113.94, 76.34, 75.25, 51.71, 51.27, 39.72, 30.89, 28.59, 28.57,
28.52, 28.50, 28.43, 22.24, 21.65, 13.06. HPLC analysis:
mobile phase iPrOH/hexane: 5/95, 35ꢀC, flow rate: 1.0
mL/min, wavelength: 210 nm; tR (retention time): 4.230 min.
m/z (ESI) 420.98 [M+]. Anal. calcd. for C24H36O6: C 68.54,
H 8.63. Found: C 68.43, H 8.69.
In this study, the ketalization reaction was started with
enantiopure (R,R)-diols, and therefore, the products were
enantiopure and of (R,R)-configuration because the two
chiral centers are not directly involved in the reactions.
The (R,R)-configuration of chiral 1,3-dioxolanes was
checked once again by comparing the retention times of
(R,R)- and (S,S)-enantiomers of racemic 1,3-dioxolanes,
which were resolved on chiral HPLC.
These compounds can be used as chiral building blocks
and starting materials for natural, cosmetic, and pharma-
ceutical purposes as seen in the synthesis of (R)-muscone
[2]. In subsequent study, we plan to examine their possible
pharmacological activities.
Dimethyl 2-phenyl-2-undecyl-1,3-dioxolane-4,5-dicarboxylate
(rac-3). This compound was synthesized by the same afore-
mentioned reaction of 1a with racemic 2c. The spectroscopic data
[IR, NMR (1H, 13C), mass spectrometry (MS), elemental analysis]
are equal to 3.
Diisopropyl (4R,5R)-2-phenyl-2-undecyl-1,3-dioxolane-4,5-
dicarboxylate (4). Yield 0.356 g (75%), light yellow oil and
>99% ee. [a]D20 +12 (c 1,CHCl3). IR nmax (neat)/cmÀ1 3050,
1
2946, 2865, 1754, 1456, 1375, 1266, 1212, 1104, 725. H-NMR
(400 MHz, CDCl3): d 7.26–7.51 (5H, m), 5.10–5.17 (1H, heptet,
J = 6.35 Hz), 4.82–4.87 (1H, heptet, J = 6.35 Hz), 4.67 (2H, s),
1.97 (2H, t, J = 7.3 Hz), 1.29–1.30 (6H, d, J = 6.35 Hz), 1.22–
1.27 (18H, m), 1.08–1.13 (6H, d, J = 6.35 Hz), 0.87 (3H, t, J =
7.3 Hz). 13C-NMR (125 MHz, CDCl3): d 167.44, 140.48,
127.12, 126.85, 125.00, 113.82, 76.96, 75.71, 68.61, 68.40,
39.96, 30.89, 28.47, 28.30, 22.24, 21.65, 20.69, 20.66, 20.54,
i
EXPERIMENTAL
20.37, 13.07. HPLC analysis: mobile phase PrOH/hexane: 5/95,
35ꢀC, flow rate: 1.0 mL/min, wavelength: 210 nm; tR (retention
time): 4.190 min. m/z (ESI) 477.09 [M+H+]. Anal. calcd. for
C28H44O6: C 70.56, H 9.19. Found: C 70.38, H 9.19.
All reagents (materials) were obtained from commercial sup-
pliers and used as provided without further purification. Toluene
was dried over sodium. The reactions were monitored with a thin
layer chromatography (TLC) plate (Merck 60 F-254). Column
chromatography was performed on silica gel 60 (70–230 mesh).
1H- and 13C-NMR spectra were measured in CDCl3 and recorded
on a Varian (400 MHz) Spectrometer with tetramethylsilane
(TMS) as the internal standard. Mass spectra (electrospray ioniza-
tion (ESI)) were recorded on Thermo Finnigen Spectrometer. In-
frared (IR) spectra were recorded on a Mattson 1000 series
spectrometer as thin films between NaCl plates. Optical rotations
were measured on a Optical Activity AA-55 digital polarimeter
and were average of more than five measurements. Enantiomeric
purities of 1,3-dioxolanes were determined by chiral HPLC anal-
yses. HPLC analysis was carried out using a Daicel CHIRALCEL
OD column with a Schimatzu system.
Diisopropyl 2-phenyl-2-undecyl-1,3-dioxolane-4,5-dicarbox-
ylate (rac-4). This compound was synthesized by the same
aforementioned reaction of 1a with racemic 2d. The
spectroscopic data [IR, NMR (1H, 13C), MS, elemental analysis]
are equal to 4.
Dimethyl (4R,5R)-2-phenyl-2-dodecyl-1,3-dioxolane-4,5-dicar-
boxylate (5). Yield 0.348 g (80%), light yellow oil and >99%
ee. [a]2D0 +22 (c 1,CHCl3). IR nmax (neat)/cmÀ1 3060, 2946,
1
2892, 1754, 1456, 1239, 1104, 1050, 752, 725. H-NMR (400
MHz, CDCl3): d 7.31–7.48 (5H, m), 4.76–4.81 (2H, dd, J =
5.85 Hz), 3.83 (3H, s), 3.53 (3H, s), 1.97 (2H, t, J = 7.3 Hz),
1.22–1.39 (20H, m), 0.87 (3H, t, J = 7.3 Hz). 13C-NMR (125
MHz, CDCl3): d 168.33, 139.93, 127.2, 126.86, 124.96,
113.94, 76.34, 75.25, 51.71, 51.27, 39.72, 30.89, 28.61, 28.59,
28.57, 28.52, 28.50, 28.43, 22.24, 21.65, 13.06. HPLC
General procedure for the synthesis of 1,3-dioxolanes (3–
12 and rac-3–12). A mixture of ketone (1.0 mmol), trimethy-
lorthoformate (0.11 mL, 1.0 mmol), Montmorillonite K-10
(300 mg), and sodium dried toluene (20.0 mL) was taken in a
round-bottomed flask fitted with a Dean-Stark apparatus to stir
for 1 h, then diol was added (2.0 mmol) and refluxed at 2 h
(Entries 1–6)—4 h (Entries 7–10) with removing the methanol.
The progress of the reaction was monitored by TLC. After
i
analysis: mobile phase PrOH/hexane: 5/95, 35ꢀC, flow rate:
1.0 mL/min, wavelength: 210 nm; tR (retention time): 4.320
min. m/z (ESI) 434.71 [M+]. Anal. calcd. for C25H38O6:
C 69.10, H 8.81. Found: C 69.06, H, 8.80.
Dimethyl 2-phenyl-2-dodecyl-1,3-dioxolane-4,5-dicarboxy-
late (rac-5). This compound was synthesized by the same
aforementioned reaction of 1b with racemic 2c. The
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

September 2012
Synthesis of New Chiral and Racemic 1,3-Dioxolanes
1069
spectroscopic data [IR, NMR (1H, 13C), MS, elemental analysis]
are equal to 5.
spectroscopic data [IR, NMR (1H, 13C), MS, elemental analysis]
are equal to 8.
Diisopropyl (4R,5R)-2-phenyl-2-dodecyl-1,3-dioxolane-4,5-
dicarboxylate (6). Yield 0.377 g (77%), light yellow oil and
>99% ee. [a]D20 +12 (c 1,CHCl3). IR nmax (neat)/cmÀ1 3050,
2946, 2865, 1754, 1456, 1375, 1266, 1212, 1104, 725. 1H-
NMR (400 MHz, CDCl3): d 7.26–7.51 (5H, m), 5.10–5.17
(1H, heptet, J = 6.35 Hz), 4.82–4.87 (1H, heptet, J = 6.35
Hz), 4.67 (2H, s), 1.97 (2H, t, J = 7.3 Hz), 1.29–1.30 (6H, d,
J = 6.35 Hz), 1.22–1.27 (20H, m), 1.08–1.13 (6H, d, J = 6.35
Hz), 0.87 (3H, t, J = 7.3 Hz). 13C-NMR (125 MHz, CDCl3): d
167.44, 140.48, 127.12, 126.85, 125.00, 113.82, 76.96, 75.71,
68.61, 68.40, 39.96, 30.89, 28.57, 28.47, 28.30, 22.24, 21.65,
20.69, 20.66, 20.54, 20.37, 13.07. HPLC analysis: mobile
Dimethyl (4R,5R)-2-(4-methylphenyl)-2-dodecyl-1,3-dioxolane-
4,5-dicarboxylate (9). Yield 0.376 g (84%), light yellow oil
and >99% ee. [a]D20 +18 (c 1,CHCl3). IR nmax (neat)/cmÀ1
2946, 2892, 1754, 1510, 1483, 1375, 1266, 1104, 1050, 833,
752. 1H-NMR (400 MHz, CDCl3): d 7.26–7.28 (2H, d, J =
7.8 Hz), 7.03–7.05 (2H, d, J = 7.8 Hz), 4.67–4.72 (2H, dd, J
= 5.85 Hz), 3.76 (3H, s), 3.48 (3H, s), 2.25 (3H, s), 1.86
(2H, t, J = 7.3 Hz), 1.14–1.18 (20H, m), 0.80 (3H, t, J = 6.8
Hz). 13C-NMR (125 MHz, CDCl3): d 169.59, 138.22, 138.14,
128.40, 126.13, 115.26, 77.50, 76.41, 52.95, 52.52, 40.97,
29.84, 29.83, 29.76, 29.74, 29.70, 29.66, 29.63, 29.51,
23.49, 22.88, 21.32, 14.29. HPLC analysis: mobile phase
iPrOH/hexane: 3/97, 35ꢀC, flow rate: 1.0 mL/min, wavelength:
210 nm; tR (retention time): 5.312 min. m/z (ESI) 471.18
[M+Na+]. Anal. calcd. for C26H40O6: C 69.61, H 9.59. Found:
C 69.36, H 8.87.
i
phase PrOH/hexane: 5/95, 35ꢀC, flow rate: 1.0 mL/min,
wavelength: 210 nm; tR (retention time): 4.380 min. m/z (ESI)
490.40 [M+]. Anal. calcd. for C29H46O6: C 70.99, H 9.45.
Found: C 70.78, H 9.44.
Diisopropyl 2-phenyl-2-dodecyl-1,3-dioxolane-4,5-dicarbox-
ylate (rac-6). This compound was synthesized by the same
aforementioned reaction of 1b with racemic 2d. The
spectroscopic data [IR, NMR (1H, 13C), MS, elemental analysis]
are equal to 6.
Dimethyl 2-(4-methylphenyl)-2-dodecyl-1,3-dioxolane-4,5-
dicarboxylate (rac-9). This compound was synthesized the by
the same aforementioned reaction of 1d with racemic 2c. The
spectroscopic data [IR, NMR (1H, 13C), MS, elemental analysis]
are equal to 9.
Dimethyl (4R,5R)-2-phenyl-2-tridecyl-1,3-dioxolane-4,5-dicar-
boxylate (7). Yield 0.376 g (84%), light yellow oil and >99%
ee. [a]2D0 +20 (c 1,CHCl3). IR nmax (neat)/cmÀ1 3060, 2892,
Diisopropyl (4R,5R)-2-(4-methylphenyl)-2-dodecyl-1,3-diox-
olane-4,5- dicarboxylate (10). Yield 0.356 g (75%), light
yellow oil and >99% ee. [a]2D0 +14 (c 1,CHCl3). IR nmax
(neat)/cmÀ1 2946, 2892, 1754, 1456, 1239, 1104, 1050, 833,
752. 1H-NMR (400 MHz, CDCl3): d 7.30–7.31 (2H, d, J =
8.3 Hz), 7.03–7.04 (2H, d, J = 8.3 Hz), 4.03–5.10 (1H,
heptet, J = 6.35 Hz), 4.76–4.90 (1H, heptet, J = 6.35 Hz),
4.58 (2H, s), 2.24 (3H, s), 1.88 (2H, t, J = 7.3 Hz), 1.21–
1.22 (6H, d, J = 6.35 Hz), 1.14–1.16 (20H, m), 1.01–1.07
(6H, d, J = 6.35 Hz), 0.80 (3H, t, J = 7.3 Hz). 13C-NMR
1
1754, 1456, 1239, 1104, 1050, 752, 725. H-NMR (400 MHz,
CDCl3): d 7.19–7.40 (5H, m), 4.69–4.74 (2H, dd, J = 5.85
Hz), 3.76 (3H, s), 3.46 (3H, s), 1.90 (2H, t, J = 7.3 Hz), 1.14–
1.22 (22H, m), 0.80 (3H, t, J = 7.3 Hz). 13C-NMR (125 MHz,
CDCl3): d 168.33, 139.91, 127.30, 126.86, 124.96, 113.93,
76.33, 75.23, 51.74, 51.29, 39.71, 30.90, 28.65, 28.62, 28.61,
28.59, 28.52, 28.50, 28.43, 28.33, 22.23, 21.66, 13.07. HPLC
i
analysis: mobile phase PrOH/hexane: 5/95, 35ꢀC, flow rate:
(125 MHz, CDCl3): d 168.71, 138.73, 138.02, 128.75,
1.0 mL/min, wavelength: 210 nm; tR (retention time): 4.250
min. m/z (ESI) 449.33 [M+H+]. Anal. calcd. for C26H40O6: C
69.61, H 8.99. Found: C 68.35, H 8.85.
Dimethyl 2-phenyl-2-tridecyl-1,3-dioxolane-4,5-dicarboxylate
(rac-7). This compound was synthesized by the same
aforementioned reaction of 1c with racemic 2c. The
spectroscopic data [IR, NMR (1H, 13C), MS, elemental analysis]
are equal to 7.
Diisopropyl (4R,5R)-2-phenyl-2-tridecyl-1,3-dioxolane-4,5-
dicarboxylate (8). Yield 0.356 g (75%), light yellow oil and
>99% ee. [a]D20 +14 (c 1,CHCl3). IR nmax (neat)/cmÀ1 3050,
2946, 2892, 1754, 1456, 1375, 1294, 1212, 1104, 752, 725.
1H-NMR (400 MHz, CDCl3): d 7.19–7.43 (5H, m), 5.03–
5.10 (1H, heptet, J = 6.35 Hz), 4.74–4.81 (1H, heptet, J =
6.35 Hz), 4.60 (2H, s), 1.89 (2H, t, J = 7.3 Hz), 1.21–1.23
(6H, d, J = 6.35 Hz), 1.14–1.17 (22H, m), 0.99–1.06 (6H, d,
J = 6.35 Hz), 0.80 (3H, t, J = 7.3 Hz). 13C-NMR (125 MHz,
CDCl3): d 168.67, 141.69, 128.35, 128.07, 126.22, 115.04,
78.17, 76.91, 69.82, 69.62, 41.18, 32.13, 29.87, 29.85, 29.84,
29.82, 29.76, 29.75, 29.69, 29.55, 23.46, 22.89, 21.92,
21.59, 14.30. HPLC analysis: mobile phase iPrOH/hexane:
5/95, 35ꢀC, flow rate: 1.0 mL/min, wavelength: 210 nm;
tR (retention time): 4.513 min. m/z (ESI) 505.01 [M+H+].
Anal. calcd. for C30H48O6: C 71.39, H 9.59. Found: C 71.22,
H 9.62.
126.17, 115.13, 78.12, 76.87, 69.78, 69.59, 41.18, 32.12,
29.84, 29.83, 29.80, 29.78, 29.76, 29.70, 29.55, 23.49,
22.89, 21.92, 21.60, 21.30, 14.30. HPLC analysis: mobile
i
phase PrOH /hexane: 3/97, 35ꢀC, flow rate: 1.0 mL/min,
wavelength: 210 nm; tR (retention time): 5.628 min. m/z
(ESI) 505.37 [M+H+]. Anal. calcd. for C30H48O6: C 71.39,
H 9.59. Found: C 71.42, H 9.33.
Diisopropyl 2-(4-methylphenyl)-2-dodecyl-1,3-dioxolane-4,5-
dicarboxylate (rac-10). This compound was synthesized by the
same aforementioned reaction of 1d with racemic 2d. The
spectroscopic data [IR, NMR (1H, 13C), MS, elemental analysis]
are equal to 10.
Dimethyl (4R,5R)-2-(4-methoxyphenyl)-2-tridecyl-1,3-diox-
olane-4,5- dicarboxylate (11). Yield 0.325 g (68%), light
yellow oil and >99% ee. [a]2D0 +18 (c 1,CHCl3). IR nmax
(neat)/cmÀ1 2946, 2892, 1754, 1537, 1456, 1266, 1212,
1104, 1050, 833, 779. 1H-NMR (400 MHz, CDCl3): d 7.30–
7.31 (2H, d, J = 7.8 Hz), 6.75–6.76 (2H, d, J = 7.8 Hz),
4.67–4.74 (2H, dd, J = 5.85 Hz), 3.76 (3H, s), 3.72 (3H, s),
3.49 (3H, s), 1.88 (2H, t, J = 6.84 Hz), 1.14–1.23 (22H, m),
0.80 (3H, t, J = 7.3 Hz). 13C-NMR (125 MHz, CDCl3): d
168.41, 158.57, 131.99, 130.58, 126.33, 112.20, 76.27,
75.17, 51.73, 51.34, 39.80, 30.90, 28.69, 28.66, 28.62,
28.60, 28.54, 28.51, 28.45, 28.33, 22.32, 21.66, 14.10.
i
HPLC analysis: mobile phase PrOH/hexane: 3/97, 35ꢀC,
Diisopropyl 2-phenyl-2-tridecyl-1,3-dioxolane-4,5-dicarbox-
ylate (rac-8). This compound was synthesized by the same
aforementioned reaction of 1c with racemic 2d. The
flow rate: 1.0 mL/min, wavelength: 210 nm; tR (retention
time): 5.440 min. m/z (ESI) 479.25 [M+H+]. Anal. calcd. for
C27H42O7: C 67.76, H 8.84. Found: C 67.72, H 8.61.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

1070
H. B. Küçük and A. Yusufoğlu
Vol 49
Dimethyl 2-(4-methoxyphenyl)-2-tridecyl-1,3-dioxolane-4,5-
Acknowledgments. This work was supported by Scientific
Research Projects Coordination Unit of Istanbul University.
Project number: T-892/02062006.
dicarboxylate (rac-11). This compound was synthesized by the
same aforementioned reaction of 1e with racemic 2c. The
spectroscopic data [IR, NMR (1H, 13C), MS, elemental analysis]
are equal to 11.
Diisopropyl (4R,5R)-2-(4-methoxyphenyl)-2-tridecyl-1,3-diox-
olane-4,5- dicarboxylate (12). Yield 0.347 g (65%), light yellow
oil and >99% ee. [a]2D0 +14 (c 1,CHCl3). IR nmax (neat)/cmÀ1
2973, 2892, 1754, 1619, 1510, 1483, 1375, 1266, 1104, 1050,
REFERENCES AND NOTES
[1] Bucsi, I.; Meleg, A.; Molnar, A.; Bartok, M. J Mol Catal A:
Chem 2001, 168, 47.
[2] Takabe, K.; Sugiura, M.; Asumi, Y.; Mase, N.; Yoda, H.;
Shimizu, H. Tetrahedron Lett 2005, 46, 3457.
1
833, 779. H-NMR (400 MHz, CDCl3): d 7.33–7.35 (2H, d, J =
8.3 Hz), 6.75–6.76 (2H, d, J = 8.3 Hz), 5.04–5.09 (1H, heptet, J
= 6.35 Hz), 4.77–4.82 (1H, heptet, J = 6.35 Hz), 4.58 (2H, s),
3.71 (3H, s), 1.88 (2H, t, J = 7.3 Hz), 1.21–1.23 (6H, d, J =
6.35 Hz), 1.14–1.16 (22H, m), 1.03–1.04 (6H, d, J = 5.86 Hz),
0.80 (3H, t, J = 7.3 Hz). 13C-NMR (125 MHz, CDCl3): d
168.73, 159.73, 133.87, 132.95, 127.57, 113.41, 78.11, 76.88,
69.79, 69.61, 55.43, 41.24, 32.13, 29.88, 29.86, 29.84, 29.83,
29.78, 29.75, 29.71, 29.55, 23.54, 22.88, 21.92, 21.67, 14.29.
[3] (a) Crawley, C. G.; Briggs, M. T. J Med Chem 1995, 38, 3951;
(b) Özkanlı, F.; Güney, A.; Calis, U.; Uzbay, T. Aranelm-Forach/Drug
Res 2003, 53, 758; (c) Zapata-Sudo, G.; Pontes, L. B.; Gabriel, D.;
Mendes, T. C. F.; Ribeiro, N. M.; Pinto, A. C.; Trachez, M. M.; Sudo,
R. T. Pharmacol Biochem Behav 2007, 86, 678; (d) Genta, M. T.; Villa,
C.; Mariani, E.; Loupy, A.; Petit, A.; Rizzetto, R.; Mascarotti, A.; Morini,
F.; Ferro, M. Int J Pharm 2002, 231, 11.
[4] (a) Pourjavadi, A.; Mirjalili, B. F. J Chem Res (S) 1999, 562; (b)
Patel, S. M.; Chudasama, U. V.; Ganeshpure, P. A. J Mol Catal A: Chem
2003, 194, 267; (c) Cornelis, A.; Laszlo, P. Synlett 1995, 10, 155.
[5] (a) Ponde, D.; Borate, H. B.; Sudalai, A.; Ravindranathan, T.;
Deshpande, V. H. Tetrahedron Lett 1996, 37, 4605; (b) Villemin, D.;
Labiad, B.; Hammadi, M. J Chem Soc Chem Commun 1992, 1192; (c)
Rakhmankulov, D. L.; Shavshukova, S. Y.; Latypova, F. N. Chem Het-
erocycl Comp 2005, 41, 951.
[6] (a) Banik, B. K.; Chapa, M.; Marquez, J.; Cardona, M. Tetrahe-
dron Lett 2005, 46, 2341; (b) Fkuzawa, S.; Tsuchimoto, T.; Hotaka, T.;
Hiyama, T. Synlett 1995, 1077; (c) Kawabata, T.; Mizugaki, T.; Ebitani,
K.; Kaneda, K. Tetrahedron Lett 2001, 42, 8329; (d) Ballini, R.; Bosica,
G.; Frullanti, B.; Maggi, R.; Sartori, G.; Schroer, F. Tetrahedron Lett
1998, 39, 1615; (e) Ponde, D. E.; Deshpande, V. H.; Bulbule, V. J.;
Sudalai, A.; Gajare, A. S. J Org Chem 1998, 63, 1058.
i
HPLC analysis: mobile phase PrOH/hexane: 3/97, 35ꢀC, flow
rate: 1.0 mL/min, wavelength: 210 nm; tR (retention time):
5.770 min. m/z (ESI) 535.65 [M+]. Anal. calcd. for C31H50O7:
C 69.63, H 9.42. Found: C 69.59, H 9.41.
Diisopropyl 2-(4-methoxyphenyl)-2-tridecyl-1,3-dioxolane-4,5-
dicarboxylate (rac-12). This compound was synthesized by the
same aforementioned reaction of 1e with racemic 2d. The
spectroscopic data [IR, NMR (1H, 13C), MS, elemental analysis]
are equal to 12.
[7] Breusch, F. L.; Oğuzer, M. Chem Berichte 1954, 87, 1225.
[8] (a) Tanaka, A.; Otsuka, S.; Yamashita, K. Agric Biol Chem
1984, 48, 2135; (b) Bruckner, R. Advanced Organic Chemistry: Reaction
Mechanisms; Harcourt/Academic Press: San Diego, 2002; pp.291, 292.
SUPPORTING INFORMATION
IR, H NMR, and 13C NMR spectra are available.
1
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet