Highly efficient 1,4-addition of 1,3-diesters to conjugated enones by In/TMSCl

Article abstract of DOI:10.1021/jo026600t

Organoindium reagents derived from indium and diethyl bromomalonates were added to a wide range of conjugated enones in a 1,4-fashion in the presence of TMSCl under mild conditions, and corresponding oxo-1,3-diesters were obtained in good to excellent yields.

Full text of DOI:10.1021/jo026600t

SCHEME 1
High ly Efficien t 1,4-Ad d ition of 1,3-Diester s
to Con ju ga ted En on es by In /TMSCl
Phil Ho Lee,* Dong Seomoon, Kooyeon Lee, and
Yunkiu Heo
Department of Chemistry, Kangwon National University,
Chunchon 200-701, Republic of Korea
phlee@kangwon.ac.kr
unique example of R,â-unsaturated ketones, the reaction
of 4-phenyl-3-buten-2-one with organoindium reagents,
produced regioselective 1,2-addition product.6a,b However,
little has been reported on the Michael addition reaction
to R,â-unsaturated ketones using allylindium reagents.
Recently, it was reported that indium-mediated addition
of allyl bromide to 1,1-dicyano-2-arylethenes gave good
yields to Michael addition products in aqueous media.7
Tetraorganoindium ate complexes reacted with R,â-
unsaturated ketones in a 1,4-addition fashion.8 The
reaction of allylic indium sesquihalides with R,â-unsatur-
ated carbonyl compounds, in which two electron-with-
drawing groups were attached to alkenes, proceeded in
a 1,2-addition mode. On the other hand, a 1,4-addition
reaction took place with 1,1-dicyano-2-arylethenes which
was extremely electron deficient olefins.9 We had re-
ported on the regioselectivity in the reactions of R,â-
enones with allylindiums.10 Despite the latest develop-
ment, there is still a strong need for a highly efficient
and mild method for 1,4-addition of 1,3-diesters to
conjugated enones. To continue our studies on the devel-
opment of efficient indium-mediated reactions,5 described
herein are our attempts to achieve this goal with an In
and TMSCl system as shown in Scheme 1.
Received October 24, 2002
Abstr a ct: Organoindium reagents derived from indium and
diethyl bromomalonates were added to a wide range of
conjugated enones in a 1,4-fashion in the presence of TMSCl
under mild conditions, and corresponding oxo-1,3-diesters
were obtained in good to excellent yields.
The Michael reaction is one of the most efficient
methods for C-C bond formation and has wide applica-
tions in organic synthesis.1 It is usually carried out with
a base as the reagent. However, it suffers from some side
reactions such as autocondensations, bis-additions, rear-
rangements, polymerizations, and 1,2-additions in the
presence of strong bases. In recent years, various re-
agents (LiI, DBN under high pressure, alumina, BiCl3,
and CdI2) were proposed to overcome these problems.2
But the high tendency of methyl vinyl ketone to polymer-
ize is a serious limitation of these reagents.3 Also,
â-disubstituted R,â-enones do not undergo smooth reac-
tions because of steric hindrance. Our interests in
extending the scope of the Michael addition reaction4 as
well as our interests in applying indium metal to modern
organic synthesis5 have led us to investigate indium-
promoted Michael addition reactions. Generally, orga-
noindium reagents reacted with R,â-unsaturated alde-
hydes to afford 1,2-addition products in good yields.6 A
In a test reaction of 2-cyclohexen-1-one (1j) with diethyl
bromomalonate (2a ), we found that transformation could
be efficiently effected by using indium in the presence of
certain additives (Table 1). A survey of various additives
revealed that the highest reactivity was achieved with
TMSCl. The use of indium trichloride or indium without
TMSCl did not produce 1,4-addition product (entries 1
* To whom correspondence should be addressed. Tel: +82 (0)33 250
8493. Fax: +82 (0)33 253 7582.
(1) (a) Bergman, E. D.; Ginsburg, D.; Pappo, R. Org. React. 1959,
10, 179. (b) Posner, G. H. Org. React. 1972, 19, 1. (c) Posner, G. H. An
Introduction to Synthesis Using Organocopper Reagents; Wiley-Inter-
science: New York, 1980. (d) Taylor, R. J . K. Synthesis 1985, 364. (e)
Lipshutz, B. H. Synthesis 1987, 325. (f) Oare. A.; Heathcock, C. H.
Topics in Stereochemistry; Interscience: New York, 1989; Vol. 19, p
227. (g) Duval, D.; Geribaldi, S. The Chemistry of Enones Part 1;
Interscience: New York, 1989; p 355. (h) Hulce, M. Org. React. 1990,
38, 225. (i) Perlmutter, P. Conjugate Addition Reactions in Organic
Synthesis; Pergamon Press: Oxford, 1992. (j) Lipshutz, B. H.; Sen-
gupta, S. Org. React. 1992, 41, 135. (k) Taylor, R. J . K. Organocopper
Reagents; Oxford University Press: Oxford, 1994.
(2) (a) Nelson, J . H.; Howells, P. N.; DeLullo, G. C.; Landen, G. L.;
Henry, R. A. J . Org. Chem. 1980, 45, 1246. (b) Ranu, B. C.; Bhar, S.
Tetrahedron 1992, 48, 1327. (c) Antonioletti, R.; Bonadies, F.; Mon-
teagudo, E. S.; Scettri, A. Tetrahedron Lett. 1991, 32, 5373. (d) Baruah,
B.; Boruah, A.; Prajapati, D.; Sandhu, J . S. Tetrahedron Lett. 1997,
38, 1449. (e) Dauben, W. G.; Gerdes, J . M. Tetrahedron Lett. 1983, 24,
3841.
(5) (a) Lee, P. H.; Bang, K.; Lee, K.; Lee, C.-H.; Chang, S. Tetrahe-
dron Lett. 2000, 41, 7521. (b) Lee, P. H.; Lee, K.; Sung, S.-Y.; Chang,
S. J . Org. Chem. 2001, 66, 8646. (c) Lee, P. H.; Lee, K.; Kim, S. Org.
Lett. 2001, 3, 3205. (d) Lee, P. H.; Sung, S.-Y.; Lee, K. Org. Lett. 2001,
3, 3201. (e) Lee, P. H.; Lee, K.; Chang, S. Synth. Commun. 2001, 31,
3189. (f) Lee, P. H.; Bang, K.; Lee, K.; Sung, S.-Y.; Chang, S. Synth.
Commun. 2001, 31, 3781. (g) Lee, P. H.; Bang, K.; Ahn, H.; Lee, K.
Bull. Korean Chem. Soc. 2001, 22, 1385. (h) Lee, P. H.; Seomoon, S.;
Lee, K. Bull. Korean Chem. Soc. 2001, 22, 1380. (i) Bang, K.; Lee, K.;
Park, Y. K.; Lee, P. H. Bull. Korean Chem. Soc. 2002, 23, 1272. (j)
Lee, P. H.; Sung, S.-Y.; Lee, K.; Chang, S. Synlett 2002, 146. (k) Lee,
K.; Seomoon, D.; Lee, P. H. Angew. Chem., Int. Ed. 2002, 41, 3901. (l)
Lee, K.; Lee, J .; Lee, P. H. J . Org. Chem. 2002, 67, 8265. (m) Iwasawa,
N.; Miura, T.; Kiyota, K.; Kusama, H.; Lee, K.; Lee, P. H. Org. Lett.
2002, 4, 4463.
(6) (a) Araki, S.; Ito, Hirokazu.; Butsugan, Y. J . Org. Chem. 1988,
53, 1833. (b) Araki, S.; Ito, H.; Katsumura, N.; Butsugan, Y. J .
Organomet. Chem. 1989, 369, 291. (c) Araki, S.; Ito, H.; Butsugan, Y.
Synth. Commun. 1988, 453.
(3) Huffman, J . W.; Potnis, S. M.; Satish, A. V. J . Org. Chem. 1985,
50, 4266.
(4) (a) Lee, P. H.; Shim, S. C.; Kim, S. Bull. Korean Chem. Soc. 1986,
7, 425. (b) Kim, S.; Lee, P. H.; Tetrahedron Lett. 1988, 29, 5413. (c)
Kim, S.; Lee, P. H.; Kim, S. S. Bull. Korean Chem. Soc. 1989, 10, 218.
(d) Kim, S.; Lee, P. H. Bull. Korean Chem. Soc. 1992, 13, 580. (e) Lee,
P. H.; Cho, M.; Han, I.-S.; Kim, S. Tetrahedron Lett. 1999, 40, 6975.
(f) Lee, P. H.; Park, J .; Lee, K.; Kim, H.-C. Tetrahedron Lett. 1999, 40,
7109.
(7) Wang, L.; Sun, X.; Zhang, Y. Synth. Commun. 1998, 28, 3263.
(8) Araki, S.; Shimizu, T.; J in, S.-J .; Butsugan, Y. Chem. Commun.
1991, 824.
(9) Araki, S.; Horie, T.; Kato, M.; Hirashita, T.; Yamamura, H.;
Kawai, M. Tetrahedron Lett. 1999, 40, 2331.
(10) Lee, P. H.; Ahn, H.; Lee, K.; Sung, S.-Y.; Kim, S. Tetrahedron
Lett. 2001, 42, 37.
10.1021/jo026600t CCC: $25.00 © 2003 American Chemical Society
Published on Web 02/14/2003
2510
J . Org. Chem. 2003, 68, 2510-2513

TABLE 1. Exa m in a tion of Op tim u m Con d ition
TABLE 2. Rea ction s of r,â-En on es w ith Or ga n oin d iu m
in th e P r esen ce of TMSCl
entry
equiv of TMSCl
5.0
In reagent
isolated yielda (%)
1
2
3
4
5
6
7
8
9
InCl3
InCl3
In
0
0
0
1.0
1.0
1.0
5.0
5.0
5.0
5.0
5.0
Inb
In
0
6c,d
22c
0
In
Inb
Ine
In
36
80d
92
0f
10
11
In
In
a
Reaction performed in the presence of TMSCl, 1 equiv of In,
and 1.5 equiv of diethyl bromomalonate in THF at room temper-
b
ature for 30 min. 0.1 equiv of In was used. c Yield of 1,2-addition
d
product. 1.0 equiv of diethyl bromomalonate was used. e 0.5 equiv
of In was used. f CH2Cl2 was used as a solvent.
and 3). The use of indium trichloride did not provide the
desired compound 3j in the presence of TMSCl as an
additive (entry 2). Although the use of 1.0 equiv of TMSCl
produced 1,2-addition product in low yield (entries 5 and
6), we could obtain the desired product 3j in 92% yield
with 1 equiv of indium and 5 equiv of TMSCl within 30
min at room temperature (entry 10). Test reactions with
a catalytic amount of indium did not proceed despite the
use of TMSCl (entries 7 and 8). THF was the solvent
chosen from several reaction media screened.
To demonstrate the efficiency and scope of the present
method, we applied the optimum conditions to a variety
of R,â-enones. The results are summarized in Table 2.
As shown in Table 2, this new recipe for 1,4-addition
reaction of diethyl bromomalonate to conjugated enones
could be applied to a broad range of substrates. For
example, methyl vinyl ketone reacted with organoindium
derived from indium and diethyl bromomalonate in the
presence of TMSCl to give the 1,4-addition product 3a
in 80% yield (entry 1). In addition to methyl vinyl ketone,
several other â-substituted acyclic enones also served as
good Michael acceptors (entries 2-7). It should be noted
that mesityl oxide, in which a â-dimethyl group was
attached, was treated with indium reagent to produce
3g in 88% yield under mild conditions (25 °C, 30 min)
despite steric hindrance (entry 7). We next explored the
possibility of cyclic R,â-enones. Several cyclic R,â-enones
underwent a novel Michael addition with the same
efficiency. 2-Cyclopenten-1-one reacted with organoin-
dium to give 1,4-addition product in 92% yield (entry 8).
Treatment of 2-methyl-2-cyclopenten-1-one with orga-
noindium gave 3i in 93% yield (entry 9). In the case of
3-methyl-2-cyclohexen-1-one and 4,4-dimethyl-2-cyclo-
hexen-1-one having steric hindrance, the desired products
3k and 3l were produced in 89% and 86% yields,
respectively, under optimum conditions (entries 11 and
12). 2-Cyclohepten-1-one was treated with organoindium
to give 3m in 82% yield (entry 13). 1-Acetylcyclohexene,
in which planarity was weak, reacted with organoindium
to afford 1,4-addition product 3n (entry 14). It may be
a
Diastereomeric ratio.
worth noting that the reaction of 3-methylene-2-norbor-
nanone with indium reagent gave the corresponding
compound 3o in an excellent yield (entry 15.)
J . Org. Chem, Vol. 68, No. 6, 2003 2511

to the residual signals of this solvent (δ 7.24 for 1H and δ 77.0
for 13C). High-resolution mass spectra were recorded on a VG
Autospec Ulpima. Infrared spectra were recorded on a J ASCO
FT/IR-460 plus FT-IR spectrometer as either a thin film pressed
between two sodium chloride plates or as a solid suspended in
a potassium bromide disk.
With these results in hand, we carried out the reaction
of 2-cyclohexen-1-one (1j) with organoindium derived
from indium and dimethyl dibromomalonate (2c) in the
presence of TMSCl, which resulted in the desired product
5 in 84% yield (eq 1). Treatment of 1j with indium and
diethyl 2-bromo-2-methylmalonate (2b) afforded 6 in 86%
yield. In the case of diethyl chloromalonate and ethyl
2-chloroacetoacetate, 1,4-addition products were not pro-
duced under the present conditions.
Typ ica l Exp er im en ta l P r oced u r e. Indium (114.8 mg, 1.0
mmol), diethyl bromomalonate (359.0 mg, 1.5 mmol) ,and TMSCl
(543.2 mg, 5.0 mmol) in THF (1 mL) were slowly added to
2-cyclohexen-1-one (96.1 mg, 1.0 mmol) in THF (1 mL) at room
temperature under a nitrogen atmosphere. After 30 min, the
reaction mixture was quenched with NaHCO3 (satd aq). The
aqueous layer was extracted with diethyl ether (3 × 20 mL),
and the combined organics were washed with water and brine,
dried with MgSO4, filtered, and concentrated under reduced
pressure. The residue was purified with silica gel column
chromatography (EtOAc/hexane ) 1:10) to give diethyl 2-(3′-
oxocyclohexyl)malonate (235.7 mg, 92%): 1H NMR (400 MHz,
CDCl3) δ 4.24-4.18 (m, 4H), 3.30 (d, J ) 7.9 Hz, 1H), 2.56-
2.50 (m, 1H), 2.47-2.39 (m, 2H), 2.31-2.21 (m, 2H), 2.11-2.05
(m, 1H), 1.96 (d, J ) 13.14 Hz, 1H), 1.72-1.66 (m, 1H), 1.56-
1.50 (m, 1H), 1.30-1.26 (m, 6H); 13C NMR (400 MHz, CDCl3) δ
209.66, 167.89, 167.80, 77.23, 61.56, 56.92, 45.12, 41.04, 38.03,
28.80, 24.56, 14.10; IR (film) 1748, 1729, 1715, 1267, 1173, 1158
cm-1; HRMS (EI) calcd for C13H20O5M+ 256.1311, found 256.1303.
Eth yl 2-eth oxyca r bon yl-5-oxoh exa n oa te (3a ): 1H NMR
(400 MHz, CDCl3) δ 4.23-4.16 (m, 4H), 3.39 (t, J ) 7.32 Hz,
1H), 2.55 (t, J ) 7.28 Hz, 2H), 2.18-2.13 (m, 5H), 1.26 (t, J )
7.15 Hz, 6H); 13C NMR (400 MHz, CDCl3) δ 207.60, 169.52,
61.83, 51.06, 40.85, 30.32, 22.82, 14.44; IR (film) 1746, 1728,
1267, 1157 cm-1; HRMS (EI) calcd for C11H18O5M+ 230.1154,
found 230.1153.
To investigate the chemoselectivity of R,â-enone and
ketone, the mixture of 2-cyclohexen-1-one and cyclohex-
anone was treated with an organoindium compound. This
treatment produced a chemoselective Michael addition
compound 3j in 76% yield and recovered cyclohexanone
in 95% yield (eq 2).
E t h yl
2-et h oxyca r b on yl-3-m et h yl-5-oxoh ep t a n oa t e
(3b): 1H NMR (400 MHz, CDCl3) δ 4.19 (q, J ) 7.13 Hz, 4H),
3.37 (d, J ) 6.69 Hz, 1H), 2.81-2.76 (m, 1H), 2.66 (dd, J ) 4.72,
16.97 Hz, 1H), 2.45-2.37 (m, 3H), 1.27 (t, J ) 7.11 Hz, 6H),
1.11-1.02 (m, 6H); 13C NMR (400 MHz, CDCl3) δ 209.97, 168.66,
168.62, 61.27, 56.27, 46.30, 36.33, 28.98, 17.76, 14.10, 7.75; IR
(film) 1746, 1727, 1277, 1253 cm-1; HRMS (EI) calcd for
C13H22O5M+ 258.1467, found 258.1440.
2-Cyclohexen-1-one did not react with carbanion de-
rived from diethyl malonate and sodium hydride in the
presence of TMSCl. Also, the reaction of organoindium
reagent derived from indium and diethyl bromomalonate
with 2-cyclohexen-1-one in the presence of TMSCl as an
additive and TEMPO as a radical scavenger did not
produce the desired product. With these results in hand,
although the mechanism of the present reaction is not
clear, we assume that this reaction proceeds not through
carbanion but radical species. These and other plausible
mechanistic pathways are under investigation.
In conclusion, we have demonstrated that a novel
indium-mediated strategy can be achieved for a 1,4-
addition of diethyl bromomalonates to conjugated enones
in the presence of TMSCl as an additive under mild
conditions. The process is simple to conduct and provides
a diverse range of ethyl 2-ethoxycarbonyl-5-oxoalkanoates
in good to excellent yields. This protocol is an appealing
alternative to the existing two-step Michael reaction
route that requires generation of anion of diethyl mal-
onate.
E t h yl
3-n -b u t yl-2-e t h oxyca r b on yl-5-oxoh e xa n oa t e
(3c): 1H NMR (400 MHz, CDCl3) δ 4.21-4.15 (m, 4H), 3.53 (d,
J ) 5.52 Hz, 1H), 2.74 (dd, J ) 5.20, 17.21 Hz, 1H), 2.69-2.66
(m, 1H), 2.51 (dd, J ) 6.55, 17.22 Hz, 1H), 2.14 (s, 3H), 1.38-
1.24 (m, 14H), 0.87 (t, J ) 6.73 Hz, 3H); 13C NMR (400 MHz,
CDCl3) δ 207.57, 169.02, 168.75, 77.23, 61.30, 61.19, 54.04, 45.32,
33.55, 32.18, 31.72, 30.30, 26.62, 22.50, 14.10, 14.00; IR (film)
1745, 1726, 1270, 1261, 1158 cm-1; HRMS (EI) calcd for
C16H28O5M+ 300.1937, found 300.1938.
Eth yl 2-eth oxyca r bon yl-5-oxo-3-p h en ylh exa n oa te (3d ):
1H NMR (400 MHz, CDCl3) δ 7.29-7.18 (m, 5H), 4.19 (q, J )
7.13 Hz, 2H), 4.00-3.92 (m, 3H), 3.69 (d, J ) 9.88 Hz, 1H), 2.98-
2.91 (m, 2H), 2.02 (s, 3H), 1.25 (t, J ) 7.15 Hz, 3H), 1.01 (t, J )
7.11 Hz, 3H); 13C NMR (400 MHz, CDCl3) δ 206.09, 168.22,
167.65, 140.41, 128.48, 128.15, 127.22, 61.65, 61.33, 57.44, 47.44,
40.49, 30.31, 14.03, 13.76; IR (film) 2940, 1748, 1730, 1263, 1155
cm-1; HRMS (EI) calcd for C17H22O5M+ 306.1467, found 306.1464.
Eth yl 4-ben zoyl-2-eth oxyca r bon yl-3-p h en ylbu ta n oa te
(3e): 1H NMR (400 MHz, CDCl3) δ 7.89 (d, J ) 7.43 Hz, 2H),
7.53 (t, J ) 7.37 Hz, 1H), 7.42 (t, J ) 7.63 Hz, 2H), 7.27-7.15
(m, 5H), 4.24-4.15 (m, 3H), 3.95 (q, J ) 7.12 Hz, 2H), 3.82 (d,
J ) 9.75 Hz, 1H), 3.57-3.42 (m, 2H), 1.24 (t, J ) 7.15 Hz, 3H),
1.01 (t, J ) 7.14 Hz, 3H); 13C NMR (400 MHz, CDCl3) δ 197.55,
168.36, 167.74, 140.45, 136.80, 133.03, 128.54, 128.39, 128.24,
128.09, 127.13, 77.23, 61.66, 61.35, 57.59, 42.63, 40.80, 14.02,
13.76; IR (film) 1748, 1731, 1687, 1264, 1156 cm-1; HRMS (EI)
calcd for C22H24O5M+ 368.0405, found 368.1624.
Exp er im en ta l Section
Reactions were carried out in oven-dried glassware under
nitrogen atmosphere. All commercial reagents were used without
purification, and all solvents were reaction grade. THF was
freshly distilled from sodium/benzophenone under nitrogen. All
reaction mixtures were stirred magnetically and were monitored
by thin-layer chromatography using Merck silica gel 60 F254
precoated glass plates, which were visualized with UV light and
then developed using either iodine or a solution of anisaldehyde.
Flash column chromatography was carried out using Fluka silica
gel 60 (0.040-0.063 mm, 230-400 mesh). 1H NMR and 13C NMR
spectra were recorded on a Bruker DPX FT (400 MHz) spec-
trometer. Deuterated chloroform was used as the solvent, and
chemical shift values (δ) are reported in parts per million relative
E t h yl 2-et h oxyca r b on yl-5-oxo-3-(2′-t h ien yl)h exa n oa t e
(3f): 1H NMR (400 MHz, CDCl3) δ 7.14 (d, J ) 4.82 Hz, 1H),
6.89-6.87 (m, 2H), 4.26 (q, J ) 7.38 Hz, 1H), 4.22-4.16 (m, 2H),
4.05 (q, J ) 7.12 Hz, 2H), 3.74 (d, J ) 8.59 Hz, 1H), 3.00 (d, J
) 6.84 Hz, 2H), 2.09 (s, 3H), 1.25 (t, J ) 7.14 Hz, 3H), 1.12 (t,
J ) 7.09 Hz, 3H); 13C NMR (400 MHz, CDCl3) δ 205.74, 167.91,
167.57, 143.55, 126.60, 125.77, 124.22, 61.69, 61.55, 57.76, 47.96,
2512 J . Org. Chem., Vol. 68, No. 6, 2003

35.67, 30.32, 14.01, 13.86; IR (film) 1747, 1730, 1238, 1155 cm-1
HRMS (EI) calcd for C15H20O5M+ 312.1031, found 312.1043.
;
Dieth yl 2-(2′-a cetylcycloh exyl)m a lon a te (3n ): 1H NMR
(400 MHz, CDCl3) δ (isomer A) 4.22-4.12 (m, 4H), 3.74 (d, J )
11.19 Hz, 1H), 2.89-2.86 (m, 1H), 2.34-2.27 (m, 1H), 2.10 (s,
3H), 2.06-2.01 (m, 1H), 1.95-1.83 (m, 2H), 1.76-1.62 (m, 3H),
1.54-1.47 (m, 2H), 1.36-1.17 (m, 6H), (isomer B) 4.22-4.12 (m,
4H), 3.44 (d, J ) 4.32 Hz, 1H), 2.61-2.58 (m, 1H), 2.44-2.43
(m, 1H), 2.10 (s, 3H), 2.06-2.01 (m, 1H), 1.95-1.83 (m, 2H),
1.76-1.62 (m, 3H), 1.54-1.47 (m, 2H), 1.36-1.17 (m, 6H); 13C
NMR (400 MHz, CDCl3) δ (isomer A) 210.77, 168.98, 168.96,
77.23, 61.26, 61.23, 54.70, 48.51, 38.97, 29.58, 28.09, 26.23, 25.41,
21.92, 14.17, (isomer B) 211.77, 168.76, 168.63, 77.23, 61.19,
61.05, 53.58, 53.51, 37.80, 30.05, 29.44, 27.55, 25.65, 25.48, 14.10;
IR (film) 1747, 1726, 1710, 1265, 1217, 1162 cm-1; HRMS (EI)
calcd for C15H24O5M+ 284.1624, found 284.1628.
E t h yl 2-et h oxyca r b on yl-3,3-d im et h yl-5-oxoh exa n oa t e
(3g): 1H NMR (400 MHz, CDCl3) δ 4.19 (q, J ) 7.14 Hz, 4H),
3.84 (s, 1H), 2.75 (s, 2H), 2.11 (s, 3H), 1.26 (t, J ) 7.11 Hz, 6H),
1.21 (s, 6H); 13C NMR (400 MHz, CDCl3) δ 207.96, 168.55, 77.24,
60.95, 58.19, 51.79, 35.26, 31.86, 25.67, 14.10; IR (film) 1747,
1725, 1268, 1155 cm-1; HRMS (EI) calcd for C13H22O5M+
258.1467, found 258.1468.
Dieth yl 2-(3′-oxocyclop en tyl)m a lon a te (3h ): 1H NMR
(400 MHz, CDCl3) δ 4.26-4.18 (m, 4H), 3.34 (d, J ) 9.41 Hz,
1H), 2.89-2.83 (m, 1H), 2.52 (dd, J ) 18.45, 18.42 Hz, 1H), 2.38-
2.16 (m, 3H), 2.03 (dd, J ) 18.51, 18.45 Hz, 1H), 1.72-1.64 (m,
1H), 1.28 (q, J ) 6.89 Hz, 6H); 13C NMR (400 MHz, CDCl3) δ
217.18, 168.16, 168.07, 77.23, 61.64, 61.62, 56.55, 42.93, 38.22,
Diet h yl 2-(2′-oxob icyclo[2.2.1]h ep t a n -3-yl)m et h ylm a -
lon a te (3o): 1H NMR (400 MHz, CDCl3) δ 4.23-4.17 (m, 4H),
3.57 (t, J ) 7.64 Hz, 1H), 2.62 (d, J ) 7.64 Hz, 1H), 2.59 (s, 1H),
2.27-2.20 (m, 1H), 2.07-2.03 (m, 1H), 1.88-1.81 (m, 2H), 1.68
(d, J ) 10.42 Hz, 1H), 1.63-1.57 (m, 3H); 13C NMR (400 MHz,
CDCl3) δ 218.53, 169.34, 169.01, 77.22, 61.51, 51.04, 50.47, 50.37,
36.33, 27.51, 14.11, 14.09; IR (film) 1741, 1264, 1155 cm-1
HRMS (EI) calcd for C12H18O5M+ 242.1154, found 242.1152.
;
Dieth yl 2-(2′-m eth yl-3′-oxocyclop en tyl)m a lon a te (3i): 1H
NMR (400 MHz, CDCl3) isomer A δ 4.23 (q, J ) 7.13 Hz, 4H),
3.46 (d, J ) 7.02 Hz, 1H), 2.43-2.36 (m, 2H), 2.23-2.13 (m, 2H),
2.08-2.03 (m, 1H), 1.77-1.69 (m, 1H), 1.31-1.26 (m, 6H), 1.08
(d, J ) 6.99 Hz, 3H), isomer B δ 4.23 (q, J ) 7.13 Hz, 4H), 3.37
(d, J ) 11.06 Hz, 1H), 2.43-2.36 (m, 2H), 2.23-2.13 (m, 2H),
2.08-2.03 (m, 1H), 1.77-1.69 (m, 1H), 1.31-1.26 (m, 6H), 0.97
(d, J ) 7.69 Hz, 3H); 13C NMR (400 MHz, CDCl3) δ (isomer A)
218.90, 168.39, 167.97, 61.61, 61.53, 54.73, 47.66, 43.62, 36.78,
24.70, 14.13, 14.07, 13.18, (isomer B) 220.09, 168.39, 167.97,
61.67, 53.33, 44.92, 39.66, 36.90, 24.40, 14.13, 14.07, 13.18, 10.47;
IR (film) 1740, 1266, 1152 cm-1; HRMS (EI) calcd for C13H20O5M+
256.1311, found 256.1335.
38.69, 36.96, 25.71, 25.36, 21.21, 14.07; IR (film) 1743, 1269 cm-1
HRMS (EI) calcd for C15H22O5M+ 282.1467, found 282.1465.
;
Dim eth yl 2-br om o-2-(3′-oxocycloh exyl)m a lon a te (5): 1H
NMR (400 MHz, CDCl3) δ 3.83 (s, 3H), 3.82 (s, 3H), 2.67-2.61
(m, 1H), 2.55-2.51 (m, 1H), 2.42 (t, J ) 13.44 Hz, 2H), 2.31-
2.23 (m, 1H), 2.14-2.05 (m, 2H), 1.72-1.64 (m, 2H); 13C NMR
(400 MHz, CDCl3) δ 209.09, 166.41, 166.17, 67.71, 54.11, 54.03,
44.44, 43.93, 40.85, 27.54, 23.90; IR (film) 1746, 1715, 1268 cm-1
;
HRMS (EI) calcd for C11H15BrO5M+ 306.0103, found 306.0077.
Dieth yl 2-m eth yl-2-(3′-oxocycloh exyl)m a lon a te (6): 1H
NMR (400 MHz, CDCl3) δ 4.27-4.15 (m, 4H), 2.52 (tt, J ) 3.32,
12.56 Hz, 1H), 2.43-2.33 (m, 2H), 2.27-2.19 (m, 2H), 2.12-2.06
(m, 1H), 1.91 (d, J ) 12.88 Hz, 1H), 1.71-1.60 (m, 1H), 1.41 (s,
3H), 1.26 (t, J ) 7.12 Hz, 6H); 13C NMR (400 MHz, CDCl3) δ
210.33, 171.04, 170.88, 61.47, 61.41, 56.79, 43.39, 42.52, 41.15,
Dieth yl 2-(1′-m eth yl-3′-oxocycloh exyl)m a lon a te (3k ): 1H
NMR (400 MHz, CDCl3) δ 4.23-4.17 (m, 4H), 3.31 (s, 1H), 2.76
(d, J ) 13.76 Hz, 1H), 2.33-2.28 (m, 3H), 1.98-1.92 (m, 2H),
1.86-1.81 (m, 2H), 1.30-1.26 (m, 6H), 1.14 (s, 3H); 13C NMR
(400 MHz, CDCl3) δ 210.70, 167.61, 167.51, 77.22, 61.30, 61.28,
61.65, 50.93, 40.79, 40.54, 33.72, 22.34, 21.39, 14.10; IR (film)
1750, 1726, 1273, 1259, 1154 cm-1; HRMS (EI) calcd for
26.66, 24.76, 16.80, 14.05; IR (film) 1729, 1715, 1263, 1118 cm-1
HRMS (EI) calcd for C14H22O5M+ 270.1467, found 270.1464.
;
C
14H22O5M+ 270.1467, found 270.1462.
Diet h yl 2-(2′,2′-d im et h yl-5′-oxocycloh exyl)m a lon a t e
(3l): 1H NMR (400 MHz, CDCl3) δ 4.22-4.16 (m, 4H), 3.57 (d,
J ) 4.86 Hz, 1H), 2.65 (t, J ) 13.68 Hz, 1H), 2.56-2.51 (m, 1H),
2.46-2.28 (m, 3H), 1.72-1.63 (m, 2H), 1.27 (q, J ) 7.44 Hz, 6H),
1.06 (s, 6H); 13C NMR (400 MHz, CDCl3) δ 210.10, 168.87,
168.63, 77.23, 61.82, 61.44, 52.29, 45.18, 40.43, 40.05, 37.81,
33.21, 28.72, 20.16, 14.00 IR (film) 1748, 1727, 1300, 1260, 1203,
1174 cm-1; HRMS (EI) calcd for C15H24O5M+ 284.1624, found
284.1608.
Ack n ow led gm en t. This work was supported finan-
cially by a KOSEF Grant No. R02-2002-000-00046-0
from the Basic Research Program of the Korea Science
& Engineering Foundation and the CMDS at KAIST.
We thank Keuckchan Bang for the preliminary experi-
ments. The gas chromatograms were provided by GC
facility, supported by Research Center for Advanced
Mineral Aggregate Composite Products.
Dieth yl 2-(3′-oxocycloh ep tyl)m a lon a te (3m ): 1H NMR
(400 MHz, CDCl3) δ 4.24-4.18 (m, 4H), 3.31 (d, J ) 6.74 Hz,
1H), 2.61-2.47 (m, 5H), 1.97-1.87 (m, 3H), 1.57-1.37 (m, 3H),
1.28 (t, J ) 7.11 Hz, 6H); 13C NMR (400 MHz, CDCl3) δ 212.65,
168.23, 168.15, 77.23, 61.54, 57.50, 47.28, 43.61, 35.66, 34.16,
28.80, 24.46, 14.10; IR (film) 1741, 1268, 1156 cm-1; HRMS (EI)
calcd for C14H22O5M+ 270.1467, found 270.1430.
Su p p or tin g In for m a tion Ava ila ble: Spectral data of all
the new compounds. This material is available free of charge
via the Internet at http://pubs.acs.org.
J O026600T
J . Org. Chem, Vol. 68, No. 6, 2003 2513