184 J . Org. Chem., Vol. 66, No. 1, 2001
Hamed et al.
Ca r bon yla tion of Cycloh exa n on e. Carbonylation of cy-
clohexanone (0.52 mL, 5.0 mmol) gave dimethyl pimelate, 1,
and methyl 6-chlorohexanoate, 2, in relative yields of 87% and
13%, respectively, and a chemical yield of 62%. Data for 1:
1H NMR (400 MHz, CDCl3): δ 3.66 (s, 6H), 2.32 (m, 4H), 1.65
(m, 4H), 1.38 (m, 2H); 13C NMR (100 MHz, CDCl3): δ 174.0,
51.5, 33.8, 28.6, 24.6. Data for 2: 1H NMR (400 MHz, CDCl3):
δ 3.67 (s, 3H), 3.53 (t, J ) 6.60 Hz, 2H), 2.33 (t, J ) 7.35 Hz,
2H), 1.8 (q, 2H, J ) 7.80 Hz, 2H), 1.65 (q, J ) 7.80 Hz, 2H),
1.50 (m, 2H); 13C NMR (100 MHz, CDCl3): δ 173.9, 51.5, 44.8,
33.8, 32.2, 26.4, 24.2.
17a would most likely eliminate water (see following
discussion), the final observed product would probably
be 18a .
The route for the formation of the unsaturated cyclic
ketonic ester, 4, from R-hydroxy- or R-methoxycyclohex-
anone in eq 2 is most likely the same as for the other
ketones. However, as shown in eq 10, elimination of
Ca r bon yla tion of Cycloh ep ta n on e. Carbonylation of
cycloheptanone (0.59 mL, 5.0 mmol) gave dimethyl subarate
and 7-chloroheptanoate in relative yield of 90% and 10%,
respectively, and a chemical yield of 66%. Data for dimethyl
subarate: 1H NMR (400 MHz, CDCl3): δ 3.86 (s, 6H), 2.32 (t,
4H), 1.65 (m, 4H), 1.36 (m, 4H); 13C NMR (100 MHz, CDCl3):
δ 174.1, 51.5, 34.0, 28.8, 25.8. Data for methyl 7-chlorohep-
tanoate: 1H NMR (400 MHz, CDCl3): δ 3.68 (s, 3H), 3.54 (t,
2H), 2.32 (t, 2H), 1.78 (m, 2H), 1.64 (m, 2H), 1.44 (m, 2H),
1.38 (m, 2H); 13C NMR (100 MHz, CDCl3): δ 174.1, 51.5, 44.9,
33.9, 32.4, 28.4, 26.5, 24.7.
Ca r b on yla t ion of 2-Met h ylcyclop en t a n on e. Carbon-
ylation of 2-methylcyclopentanone (0.54 mL, 5.0 mmol) gave
dimethyl 2-methyl adipate and methyl 5-chlorohexanoate in
relative yields of 88% and 12%, respectively, and a chemical
yield of 62%. Data for dimethyl 2-methyl adipate: 1H NMR
(400 MHz, CDCl3): δ 3.68 (s, 3H), 3.67 (s, 3H), 2.48 (m, 1H),
2.30 (t, 2H), 1.65 (m, 3H),1.45 (m, 1H), 1.15 (d, 3H); 13C NMR
(100 MHz, CDCl3): δ 176.8, 173.7, 51.4, 51.3, 39.2, 33.6, 33.1,
22.6, 16.9. Data for methyl 5-chlorohexanoate: 1H NMR (400
MHz, CDCl3): δ 4.20 (m, 1H), 3.65 (s, 3H), 2.33 (t, 2H), 1.76
(m, 2H), 1.68 (m, 2H), 1.50 (d, 3H); 13C NMR (100 MHz,
CDCl3): δ 173.8, 50.8, 43.1, 33.7, 30.0, 24.3, 9.6.
water or methanol happens before ring cleavage can
occur. The elimination may be acid-catalyzed so in the
presence of proton sponge 19 may be the product.
In summary, this report describes a novel carbonyla-
tion of ketones that generally occurs with carbon-carbon
bond cleavage to give diesters. A side reaction is the
formation of terminally chlorine-substituted acid esters.
Exp er im en ta l Section
Gen er a l. 1H and 13C NMR data were recorded on a Varian
VXR 400S NMR. All chemical shifts are reported relative to
tetramethylsilane as internal standard. GLC analyses were
carried out using a GOW-MAC 350 gas chromatography fitted
with Carbowax 10 M on 80-100 mesh Chromosorb W-NAW
columns.
Ma ter ia ls. All chemicals were purchased from Aldrich
Chemical Co., unless otherwise specified, and were used as
received. PdCl2 and 2-methylcyclohexanone were purchased
from Alfa AEsar and used without further purification.
Methanol was distilled over magnesium alkoxide.
Ca r bon yla tion of 2-Meth ylcycloh exa n on e. Carbonyla-
tion of 2-methylcyclohexanone (0.61 mL, 5.0 mmol) gave
dimethyl 2-methylpimelate, and methyl 6-chloroheptanoate in
relative yields of 90% and 10%, respectively, and in a chemical
yield of 64%. Data for dimethyl 2-methylpimelate: 1H NMR
(400 MHz, CDCl3): δ 3.68 (s, 3H), 3.67 (s, 3H), 2.48 (m, 1H),
2.30 (t, 2H), 1.65 (m, 6H), 1.15 (d, 3H); 13C NMR (100 MHz,
CDCl3): δ 176.9, 173.8, 51.5, 51.4, 39.3, 33.9, 33.4, 26.8, 24.9,
17.2. Data for methyl 6-chloroheptanoate: 1H NMR (400 MHz,
CDCl3): δ 4.14 (m, 1H), 3.64 (s, 3H), 2.32 (t, 2H), 1.72 (m, 2H),
1.65 (m, 2H), 1.50 (d, 3H), 1.43 (m, 2H); 13C NMR (100 MHz,
CDCl3): δ 173.9, 58.5, 51.5, 39.9, 33.9, 26.2, 25.3, 24.1.
Ca r b on yla t ion of 2-H yd r oxycycloh exa n on e. Carbon-
ylation of 2-hydroxycyclohexanone (0.23 g, 2.0 mmol) gave
2-(carbomethoxy)cyclohex-2-en-1-one, 4, (0.17 g, 55%) yield.
The product was purified by column chromatography (hexane/
Gen er a l P r oced u r e for t h e P d Cl2-Ca t a lyzed Ca r -
bom eth oxyla tion of Keton es. All reactions were conducted
in dry glassware under a positive pressure of carbon monoxide
of a little over 1 atm. A two-necked round-bottom flask (100
mL) equipped with a magnetic stirring bar, septum, and
balloon was charged with CuCl2 (2.0 g, 15.0 mmol), PdCl2 (0.10
g, 0.56 mmol), and methanol (15 mL). The air in the flask was
replaced by CO by evacuating on an aspirator and then
pressuring with CO through a needle. Then 5 mmol of ketone
was injected, and the CO pressure was raised to a little over
1 atm. The reaction mixture was stirred at room temperature
for 4 days. After removing the solvent under reduced pressure,
the residue was dissolved in CH2Cl2, washed with diluted
NaHCO3 (20 mL), and dried over MgSO4. CH2Cl2 was then
removed under reduced pressure, and the residue was purified
by either preparative GLC or column chromatography (hexane/
AcOEt ) 8/2). In every reaction, 15-20% of the starting
material was recovered. The percent yields based on ketone
were obtained by GLC analysis in the presence of an internal
standard.
Ca r bon yla tion of Cyclop en ta n on e. Carbonylation of
cyclopentanone (0.45 mL, 5.0 mmol) gave dimethyl adipate and
methyl 5-chloropentanoate in relative yields of 85% and 15%,
respectively, and a chemical yield of 58%. Data for dimethyl
adipate: 1H NMR (400 MHz, CDCl3): δ 3.66 (s, 6H), 2.32 (m,
4H), 1.65 (m, 4H). 13C NMR (100 MHz, CDCl3): δ 173.8, 51.6,
33.7, 24.4. Data for methyl 5-chloropentanoate: 1H NMR (400
MHz, CDCl3): δ 3.68 (s, 3H), 3.56 (t, 2H), 2.36 (t, 2H), 1.80
(m, 4H); 13C NMR (100 MHz, CDCl3): δ 173.6, 51.6, 44.4, 33.2,
31.8, 22.2.
1
ethyl acetate ) 8/2). H NMR (400 MHz, CDCl3): δ 5.93 (t, J
) 4.76 Hz, 1H), 3.60 (s, 3H), 2.52 (t, J ) 7 Hz, 2H), 2.43 (q, J
) 5.7 Hz, 2H), 1.95 (m,2H); 13C NMR (100 MHz, CDCl3): δ
194.4, 175.0, 151.5, 116.3, 54.7, 38.8, 24.4, 23.0.
Ca r b on yla t ion of 2-Met h oxycycloh exa n on e. Carbon-
ylation of 2-methoxycyclohexanone (0.26 g, 2.0 mmol) gave
2-(carbomethoxy)cyclohex-2-en-1-one, 4, (0.11 g, 36%) yield.
Ca r bon yla tion of 2-Deca n on e. Carbonylation of 2-de-
canone afforded methyl nonanoate, 1-chlorooctane, and methyl
acetate in relative yields of 65%, 35%, and 100%, respectively,
and a chemical yield of 42%. Data for methyl nonanoate: 1H
NMR (400 MHz, CDCl3): δ 3.67 (s, 3H), 2.30 (t, 2H), 1.65 (m,
2H), 1.30 (m, 10H), 0.89 (t, 3H); 13C NMR (100 MHz, CDCl3):
δ 174.4, 51.4, 34.1, 31.8, 29.2, 29.1, 29.0, 24.9, 22.6, 14.1. Data
for 1-chlorooctane: 1H NMR (400 MHz, CDCl3): δ 3.54 (t, 2H),
1.78 (m, 2H), 1.45 (m, 2H), 1.30 (m, 8H), 0.89 (t, 3H); 13C NMR
(100 MHz, CDCl3): δ: 45.2, 32.6, 31.7, 29.1, 28.8, 27.0, 22.6,
14.1. Methyl acetate was identified by GLC retention time.
Ca r bon yla tion of 2-Meth ylcycloh exa n on e in th e P r es-
en ce of 13CO. Carbonylation of 2-methylcyclohexanone (0.52
mL, 5.0 mmol) in the presence of 13CO was carried out as
before to give dimethyl 2-methylpimelate (5) and methyl
6-chloroheptanoate in relative yield of 85% and 15%, respec-
1
tively. Analysis by H and 13C NMR showed that the product
5 is a mixture of two isomers 5a and 5b in relative yield of