Notes
J . Org. Chem., Vol. 62, No. 26, 1997 9325
1.75 mmol) in t-BuOH (7 mL) provided 4c (0.58 g, 5.29 mmol)
in 76% yield as a light yellow oil.
tuted conjugate cyclohexenones by a series of Michael
addition, aldol reaction, and decarboalkoxylation of â-keto
esters and conjugate enones (or enals) in the t-BuOK/t-
BuOH system. This highly mild reaction condition allows
for simple conjugate enones (or enals) to be used in the
annulation reaction without any polymerization. Con-
structions of bicyclic and heterocyclic compounds using
this approach are currently under investigation.
Isop h or on e (4d ).30 The reaction of 1a (0.91 g, 7 mmol) and
2d (0.69 g,7 mmol) under t-BuOK (0.20 g, 1.75 mmol) in t-BuOH
(7 mL) provided 4d (0.73 g, 5.25 mmol) in 75% yield as a light
yellow oil.
3-Eth yl-2-cycloh exen -1-on e (4e).20 The mixture of 1a (0.91
g, 7 mmol) and 2e (0.59 g, 7 mmol) under t-BuOK (0.20 g, 1.75
mmol) in t-BuOH (7 mL) was stirred at room temperature for 3
h and then heated to reflux for 3 h. After general workup and
purification, 4e (0.59 g, 4.76 mmol) was obtained in 68% yield
as a light yellow oil.
Exp er im en ta l Section
6-Meth yl-2-cycloh exen -1-on e (4f).4,27,31,32 The reaction of
1b (1.01 g, 7 mmol) and 2f (0.39 g, 7 mmol) under t-BuOK (0.20
g, 1.75 mmol) in t-BuOH (7 mL) provided 4f (0.42 g, 3.78 mmol)
in 54% yield as a light yellow oil.
Gen er a l. Ethyl 2-methyl-2-propionylacetate (1d ) was pre-
pared by following the literature procedure.21,22 All other
reagents were obtained from Aldrich Chemical Co. and used as
received. Reactions were monitored by GC and TLC on silica
gel plates (EM Science, Kieselgel 60, F254). TLC plates were
visualized by UV, iodine vapor, and phosphomolybdic acid stain.
The column chromatographies were carried out with silica gel
60, 70-230 mesh ASTM supplied by Merck. 1H NMR and 13C
NMR spectra were recorded in CDCl3 at 500 and 125 MHz,
respectively. Chemical shifts are reported in ppm downfield
from the internal standard, tetramethylsilane, and coupling
constants are given in hertz. Infrared spectra were obtained
with CH2Cl2 as a solvent. The products, cyclohexenones, were
identified by comparison of the spectral data with those reported
in the literature. 3-Methyl-2-cyclohexen-1-one and isophorone
are commercially available from Aldrich Chemical Co.
3,6-Dim eth yl-2-cycloh exen -1-on e (4 g).4,32 The reaction of
1b (1.01 g, 7 mmol) and 2c (0.49 g, 7 mmol) under t-BuOK (0.20
g, 1.75 mmol) in t-BuOH (7 mL) provided 4g (0.52 g, 4.20 mmol)
in 60% yield as a light yellow oil.
2,3-Dim eth yl-2-cycloh exen -1-on e (4h ).33 The reaction of
1c (1.01 g, 7.0 mmol) and 2c (0.49 g, 7.0 mmol) under t-BuOK
(0.35 g, 3.15 mmol) in t-BuOH (7 mL) provided 4h (0.817 g, 6.58
mmol) in 94% yield as a light yellow oil.
2,6-Dim eth yl-2-cycloh exen -1-on e (4i).32,34 The reaction of
1d (1.20 g, 7 mmol) and 2f (0.39 g, 7 mmol) under t-BuOK (0.20
g, 1.75 mmol) in t-BuOH (7 mL) provided 4i (0.29 g, 2.34 mmol)
in 33% yield as a light yellow oil.
4-Ca r beth oxy-3,5-d im eth yl-2-cycloh exen -1-on e (10). The
reaction of 1a (2.60 g, 20 mmol) and acetaldehyde (0.44 g, 10
mmol) under t-BuOK (0.28 g, 2.50 mmol) in t-BuOH (20 mL)
provided a 2.8:1 stereoisomeric mixture of 10 (1.39 g, 7.1 mmol)
in 71% yield as a light yellow oil.
Gen er a l P r oced u r e. To a stirred solution of â-keto ester 1
(1 equiv) and acyclic conjugate enone (or enal) 2 (1 equiv) in
t-BuOH (1 M) was added a catalytic amount of t-BuOK (0.05
equiv) at 0 °C. The reaction mixture was stirred at that
temperature for 30 min, and 0.2 equiv of t-BuOK was added
again. The mixture was then heated at reflux for 20 h. Upon
cooling to room temperature, the mixture was quenched with 1
M HCl (10 mL) solution, diluted with a 1:1 mixture of ether and
benzene (80 mL), washed with 1 M NaOH solution (20 mL × 3)
and brine (20 mL × 2). The separated organic layer was dried
over anhydrous Na2SO4, filtered, and concentrated under re-
duced pressure. The crude product was purified by flash column
chromatography (SiO2, 1:9-2:8 EtOAc:hexanes).
Ack n ow led gm en t. Financial support provided by
Korea Science and Engineering Foundation (grant no.
951-0301-029-2) and Regional Research Center spon-
sored by KOSEF and Kyunggi-Do is greatly acknowl-
edged.
Registr y No. (supplied by author) 1d , 759-66-0; 4a , 7214-
50-8; 4b, 5515-76-4; 4c, 1193-18-6; 4d , 78-59-1; 4e, 17299-34-2;
4f, 6610-21-5; 4g, 15329-10-9; 4h , 1122-20-9; 4i, 40790-56-5.
5-Meth yl-2-cycloh exen -1-on e (4a ).23-26 The reaction of 1a
(0.91 g, 7 mmol) and 2a (0.49 g, 7 mmol) under t-BuOK (0.20 g,
1.75 mmol) in t-BuOH (7 mL) provided 4a (0.60 g, 5.4 mmol) in
78% yield as a light yellow oil.
Su p p or tin g In for m a tion Ava ila ble: Characterization
data for cyclohexenones 3a , 4a -i, and 10, together with 1H
NMR spectra for 3a and 10 (4 pages). This material is
contained in libraries on microfiche, immediately follows this
article in the microfilm version of the journal, and can be
ordered from the ACS; see any current masthead page for
ordering information.
6-Ca r beth oxy-5-m eth yl-2-cycloh exen -1-on e (3a ). The re-
action of 1a (0.91 g, 7 mmol) and 2a (0.49 g, 7 mmol) under
EtONa (0.25 equiv, 0.12 g, 1.75 mmol) in EtOH (7 mL) produced
a 1:1 mixture of 3a (0.48 g, 2.64 mmol, 38%, a single stereoiso-
mer) and 4a (0.29 g, 2.66 mmol, 37%) as light yellow oils.
4-Meth yl-2-cycloh exen -1-on e (4b).25-28 The reaction of 1a
(0.91 g, 7 mmol) and 2b (0.49 g, 7 mmol) under t-BuOK (0.20 g,
1.75 mmol) in t-BuOH (7 mL) provided 4b (0.40 g, 3.64 mmol)
in 52% yield as a light yellow oil.
J O970145X
3-Meth yl-2-cycloh exen -1-on e (4c).26,29 The reaction of 1a
(0.91 g, 7 mmol) and 2c (0.49 g, 7 mmol) under t-BuOK (0.20 g,
(27) Dauben, W. G.; Shaffer, G. W.; Vietmeyer, N. D. J . Org. Chem.
1968, 33, 4060.
(28) Chatani, N.; Fujii, S.; Yamasaki, Y.; Murai, S.; Sonoda, N. J .
Am. Chem. Soc. 1986, 108, 7361.
(21) Wilson, G. E. J r.; Hess, A. J . Org. Chem. 1980, 45, 2766.
(22) Roberts, D. C.; McElvain, S. M. J . Am. Chem. Soc. 1937, 59,
2007.
(23) Blanchard, J . P.; Goering, H. L. J . Am. Chem. Soc. 1951, 73,
5863.
(24) Allinger, N. L.; Riew, C. K. J . Org. Chem. 1975, 40, 1316.
(25) Liotta, D.; Zima, G.; Saindane, M. J . Org. Chem. 1982, 47, 1258.
(26) Ko¨tz, A.; Steinhorst, H. J ustus Liebigs Ann. Chem. 1911, 379,
17.
(29) Rabe, P. Ber. 1907, 40, 2482.
(30) Zhou, Y. F.; Huang, N. Z. Synth. Commun. 1982, 12, 795.
(31) Reich, H. J .; Renga, J . M.; Reich, I. L. J . Am. Chem. Soc. 1975,
97, 5434.
(32) Marino, J . P.; J ae´n, J . C. J . Am. Chem. Soc. 1982, 104, 3165.
(33) J ung, M. E.; McCombs, C. A.; Takeda, Y.; Pan, Y.-G. J . Am.
Chem. Soc. 1981, 103, 6677.
(34) Ceccherelli, P.; Curini, M.; Marcotullio, M. C.; Rosati, O.;
Wenkert, E. J . Org. Chem. 1990, 55, 5, 311.