Reactivity of Enol Carbonates with Ozone
J . Org. Chem., Vol. 64, No. 18, 1999 6601
California, Santa Barbara, CA. Gas chromatographic separa-
tions were made on a 30 m SPB-30 Supelco capillary column.
3-(3-Bu ten yl)-3-m eth ylcycloh ex-1-en yl Meth yl Ca r bon -
a te (3). A. Preparation of the Grignard reagent: Magnesium
(0.40 g, 16.3 mmol) and several crystals of iodine were placed
into a dry three-neck 50 mL round-bottom flask containing a
reflux condenser and addition funnel. After the contents were
flamed, the flask was cooled under argon. A mixture of dry
ether (20 mL) and the bromide (1.38 mL, 1.84 g, 13.62 mmol)
was added dropwise from the addition funnel over a 15 min
period. The mixture was refluxed for an additional 15 min,
then cooled.
the enol carbonate (3) (0.50 g, 2.232 mmol) and dry Et2O (10
mL). After the mixture was cooled in a methanol/ice bath, the
resultant was treated dropwise with n-BuLi (4.32 mL, 1.6M,
6.91 mmol) over a period of 5 min. The resultant was stirred
for 1 h at -10 °C. After the addition of HMPA (1.55 mL, 8.93
mmol), the reaction mixture was treated by the dropwise
addition of AcCl (0.56 g, 0.51 mL, 0.713 mmol) over a 5 min
period. After being stirred at room temperature overnight, the
mixture was diluted with 25 mL of petroleum ether (30-60)
and washed five times with water and once with brine. After
drying with Na2SO4, filtration, and concentration in a rotary
evaporator, 0.53 g of material was obtained. The crude was
chromatographed on 24 g of silica gel (5% EtOAc/95% 30-60
petroleum ether eluent) to give 0.34 g (74%) of the desired
product, 7, as a colorless liquid: IR (neat) 3076.6, 1757.7,
B. Under a flow of argon, in a dried 125 mL round-bottom
flask containing an addition funnel and reflux condenser, was
added CuBr‚DMS (0.19 g, 0.91 mmol), 3-methylcyclohex-2-en-
1-one (1.03 mL, 1.0 g, 9.08 mmol), and 40 mL of dry DMS/
Et2O (50:50). The Grignard reagent was transferred via
cannula to the addition funnel and added dropwise to the 0
°C cooled solution over a period of 1.5 h. After being warmed
to room temperature for 1 h and then returned back to 0 °C,
the mixture was treated with methyl chloroformate (3.51 mL,
4.29 g, 45.4 mmol) and then allowed to stir at room temper-
ature overnight. The reaction mixture was quenched with 10
mL of NH4Cl(satd) and the layers separated. The aqueous
layer was washed once with 20 mL of ether. The combined
ethers were washed four times with 20 mL portions of NH4-
Cl(satd) and then dried with MgSO4. After concentration at
the rotary evaporator, the 2.21 g of product, which contained
carbon- and oxygen-acylated products, and the untrapped
ketone, was purified on silica gel (85 g) (4% EtOAc/96% hexane
eluent) to produce 0.91 g (45%) of the desired product, 3, as a
1
1686.7, 1640.1, 1220.0 cm-1; H NMR (CDCl3) δ 5.80 (m 1H),
5.13 (s 1H), 4.93 (m 2H), 2.10 (s 3H), 2.06 (m 4H), 1.75 (m
2H), 1.42 (m 4H), 1.02 (s 3H); 13C NMR (CDCl3) δ 169.18,
147.44, 139.20, 122.67, 113.91, 41.76, 34.64, 33.98, 28.45,
27.15, 26.77, 21.00,19.31; HRMS calcd for C13H21O2 (M + H)+
m/e 209.15416, measured 209.15407. Anal. Calcd for
C
13H20O2: C, 74.96; H, 9.68. Found: C, 75.06; H, 9.71.
Cycloh ex-1-en yl Meth yl Ca r bon a te (16). Into a 100 mL
round-bottom flask under argon was added KH (2.68 g of 35%
) 0.94 g, 23.43 mmol) as a 35% suspension in oil.23 The hydride
was washed three times with hexane and then blown dry with
argon. Dry THF (55 mL) was added with stirring. Cyclohex-
anone (2.0 g, 20.38 mmol) was added dropwise via syringe over
a 10 min period. After 15 min, the resulting gel-like material
was treated by the dropwise addition of a solution of methyl
chloroformate (2.5 g, 26.5 mmol) in THF (10 mL). After this
addition, the gel dispersed to give a light yellow solution that
was stirred at room temperature overnight. The reaction
mixture was quenched with 35 mL of Na2CO3 (satd) and then
extracted three times with 25 mL of Et2O. The combined ether
layers were washed twice with 25 mL of Na2CO3 (satd) and
once with brine and dried with MgSO4. Concentration gave
2.66 g of crude product that was chromatographed on silica
gel (130 g) using a gradient elution (2%, 3%, then 4% ethyl
acetate with 30-60 petroleum ether) to give 1.0 g (32%) of the
desired product, 16, as a colorless liquid: IR (neat) 1757.2,
colorless liquid: IR (neat) 1759.5, 1689.5, 1640.2, 1256.3 cm-1
1H NMR (CDCl3) δ 5.79 (m 1H), 5.25 (s 1H), 4.03 (m 2H), 3.80
(s 3H), 2.15 (m 4H), 1.76 (m 2H), 1.43 (m 4H), 1.02 (s 3H); 13
;
C
NMR (CDCl3) δ 153.89, 147.61, 139.05, 122.63, 113.91, 54.65,
41.64, 34.64, 33.83, 28.38, 27.00, 26.27, 19.23; HRMS calcd
for C13H21O3 (M + H)+ m/e 225.14907, measured 225.14831.
Anal. Calcd for C13H20O3: C, 69.61; H, 8.99. Found: C, 69.73;
H, 8.77.
3-(3-Bu ten yl)cycloh ex-1-en yl Meth yl Ca r bon a te (5).22
As in the preparation of enol carbonate (3), the Grignard
reagent was prepared from 4-bromo-1-butene (10.1 g, 74.8
mmol) and magnesium (3.6 g, 148.1 mmol) in dry ether (30
mL). Under argon and with cooling (0 °C), the Grignard
reagent was added dropwise over a period of 1.5 h to cyclohex-
2-en-1-one (4.42 g, 46.0 mmol) and copper bromide (0.76 g, 5.30
mmol) in dry ether (20 mL). After an additional 1 h of stirring
at 0 °C, dry HMPA (40 mL) was added, followed by the
dropwise addition of methyl chloroformate (48.0 g, 508 mmol)
at such a rate that the exotherm of the reaction was controlled.
After being stirred to room temperature overnight, the mixture
was poured into saturated NH4Cl (100 mL) and extracted three
times with 50 mL of ether. The ether extract was washed four
times with 30 mL water and once with 30 mL of brine and
then dried with MgSO4. After concentration at the rotary
evaporator, the 6.71 g of product was impregnated on silica
gel (20 g) and loaded onto and purified from silica gel (100 g)
(4% EtOAc/96% hexane eluent) to produce 0.66 g (7%) of the
desired product, 5, as a colorless liquid: IR (neat) 1759.5,
1
1692.6, 1441.5, 1259.6 cm-1; H NMR (CDCl3) δ 5.42 (m 1H),
3.80 (s 3H), 2.18 (m 2H), 2.11 (m 2H), 1.75 (m 2H), 1.58 (m
2H); 13C NMR (CDCl3) δ 153.90, 148.41, 113.84, 54.62, 26.15,
23.33, 22.38, 21.38; mass spectrum m/e 156 (M+); HRMS calcd
for C8H12O3 (M+) 156.07864, measured 156.07819 Anal. Calcd
for C8H12O3: C, 61.52; H, 7.74. Found: C, 61.70; H, 7.87.
Gen er a l P r oced u r e for th e Ozon olysis of Dien es 3, 5,
a n d 7 a n d th e Ch a r a cter iza tion of Ald eh yd es 4, 6, a n d
8. Into a 100 mL round-bottom flask containing a gas disper-
sion tube were added the diene (1.0 mmol) and CH2Cl2 (30
mL), followed by a trace of Sudan Red 7B dye (sufficient to
impart a pale burgundy color).24 Nitrogen was bubbled through
the solution, which was then cooled to -78 °C. The nitrogen
line was replaced with a line from the ozone generator, and a
stream was delivered over a 5 min period until the burgundy
color began to change toward that of a white zinfandel. The
ozone line was quickly removed and the nitrogen stream
replaced. After 20 min under a stream of nitrogen, the gas
dispersion tube was removed and replaced by a magnetic
stirring bar. Zinc dust (1.0 g, 15.3 mmol) was added, followed
by 2 mL of glacial acetic acid. The cooling bath was removed
and the flask allowed to warm to room temperature. The
solution was filtered through diatomaceous earth and concen-
trated at the rotary evaporator. The residue was flashed
through a plug of silica gel with CH2Cl2 and concentrated to
give the pure aldehyde product. The structure of these
1
1686.9, 1654.3, 1265.6 cm-1; H NMR (CDCl3) δ 5.79 (m 1H),
5.40 (m 1H), 4.97 (m 2H), 3.79 (m 3H), 2.16 (m 5H), 1.75 (m
3H), 1.44 (m 2H), 1.18 (m 1H); 13C NMR (CDCl3) δ 153.97,
148.62, 138.49, 118.30, 114.51, 54.77, 34.97, 33.75, 31.00,
27.96, 26.42, 21.27; mass spectrum (M + H)+ m/e 211; HRMS
calcd for
209.11834. Anal. Calcd for
Found: C, 68.32; H, 8.43.
C
12H17O3 (M - H)+ m/e 209.11777, measured
C12H18O3: C, 68.54; H, 8.63.
1
3-(3-Bu ten yl)-3-m eth ylcycloh ex-1-en ol Aceta te (7). Un-
der argon, into a dry three-neck round-bottom flask was added
compounds was consistent with their infrared, H NMR, and
mass spectra. In addition, they corresponded to those reported
by Danishefsky9 and were interconvertible with their dienes
(22) Attempts to directly trap the potassium enolate, itself prepared
by the potassium/ammonia reduction of the corresponding R,â-unsatur-
ated enone, also produced very low yields of the enol carbonate product,
with the untrapped saturated ketone predominating. We are currently
investigating the potassium/ammonia reduction of R,â-unsaturated
ketones and will report on that in the future.
(23) The use of KH to generate enolates is described: Brown, C. A.
J . Org. Chem. 1974, 39, 3913-3918.
(24) The use of the Sudan dyes in ozonolysis is described: Veysoglu,
T.; Mitscher, L. A.; Swayze, J . K. Synthesis 1980, 807-810.