Organic Syntheses, CV 8, 377
[1,2-Cyclopentanedicarboxylic acid, 1-methyl-, cis-(±)-]
Submitted by Jean-Pierre Deprés and Andrew E. Greene
1.
Checked by Scott K. Thompson, Gregory A. Slough, and Clayton H. Heathcock.
1. Procedure
A.
7,7-Dichloro-1-methylbicyclo[3.2.0]heptan-6-one. A
500-mL, two-necked, round-bottomed flask is equipped with a
Teflon-covered magnetic stirring bar, a
250-mL pressure-equalizing addition funnel topped with a gas inlet, and a
condenser connected to a
Nujol-filled bubbler (Note
1). The system is flushed with
nitrogen (Note
2). The flask is then charged with
10.0 g (ca. 150 mmol) of zinc–copper couple (Note
3),
200 mL of anhydrous ether (Note
4), and
10.5 mL (8.2 g, 100 mmol) of 1-methyl-1-cyclopentene (Note
5), and the addition funnel is filled with a solution of
13.4 mL (21.8 g, 120 mmol)
of trichloroacetyl chloride (Note
5) and
11.2 mL (18.4 g, 120 mmol) of phosphorus oxychloride (Note
6) in
100 mL of anhydrous ether. Magnetic stirring is begun and the solution is added dropwise over 1 hr to the reaction flask at room temperature. After being stirred for an additional 14 hr, the reaction mixture is filtered under
water pump pressure through 30 g of filter aid, which is then washed with
120 mL of ether. The filtrate is concentrated to ca. 100–120 mL, treated with
400 mL of hexane, and then briefly stirred to precipitate the
zinc chloride. The supernatant solution is transferred to a
separatory funnel and the viscous residue is washed with two
75-mL portions of
3 : 1 hexane–ether. The combined solution is washed successively with 200 mL of cold water,
200 mL of saturated aqueous sodium bicarbonate solution, and 2 ×
50 mL of saturated aqueous sodium chloride solution, dried over anhydrous
sodium sulfate, and concentrated to dryness by rotary evaporation at 25°C to give
17.0–17.8 g of a brown oil. Vacuum distillation of this material without fractionation provides
14.9–16.0 g (
77–83%) of
7,7-dichloro-1-methylbicyclo[3.2.0]heptan-6-one as a clear, light-yellow oil, bp
38°C (0.2 mm),
nD20 1.4970 (Note
7).
B.
cis-1-Methylcyclopentane-1,2-dicarboxylic acid. A
1-L, one-necked, round-bottomed flask (Note
1) equipped with a Teflon-covered magnetic stirring bar is flushed with
nitrogen and then charged with
300 mL of dry tetrahydrofuran (Note
4) and
14.5 g (75 mmol) of 7,7-dichloro-1-methylbicyclo[3.2.0]heptan-6-one. The flask is capped with a septum and connected to a Nujol bubbler and to a
nitrogen line by means of syringe needles (Note
2). To the stirred solution cooled in a
dry ice–acetone bath is added by syringe over 5 min
33.2 mL (83 mmol) of a 2.50 M solution of butyllithium in hexane (Note
8). After being stirred for 15 min with continued cooling, the reaction mixture is treated with
14.2 mL (150 mmol) of
acetic anhydride all at once (Note
9). The cooling bath is removed and the reaction mixture is allowed to warm to room temperature and then stirred for an additional 1 hr. Most of the solvent and excess
acetic anhydride are directly removed with a
rotary evaporator at 25°C under water pump pressure (Note
10). The resulting solid residue is further dried for 15–30 min at 4 mm and then dissolved in a mixture of
100 mL of acetonitrile, 100 mL of carbon tetrachloride, and 150 mL of distilled water. The mixture is cooled in an
ice bath and, with efficient stirring, treated with
40.1 g (187 mmol) of sodium periodate and
346 mg (1.5 mmol) of ruthenium(III) chloride hydrate (Note
11). After 15 min, the cooling bath is removed (Note
12) and stirring is continued for 5 hr,
whereupon the thick mixture is treated with
200 mL of 10% aqueous sodium hydroxide solution and then extracted in a separatory funnel with
500 mL of 1 : 1 ether–hexane (Note
13). The phases are separated and to the aqueous phase is added
900 mL of 2 : 1 ether–ethyl acetate followed by a
2 N aqueous hydrochloric acid solution until a pH of 2–3 is obtained (Note
14). After being vigorously agitated, the phases are separated and the organic phase is washed successively with solutions of
3% aqueous sodium thiosulfate (Note
15) and saturated aqueous
sodium chloride. All aqueous phases are mixed and, at pH 2 to 3, extracted with
1 L of 3 : 2 ether–ethyl acetate,
which is then washed as before. The
ether–
ethyl acetate solutions are combined and dried over anhydrous
sodium sulfate and the solvents are removed by rotary evaporation to leave a light-yellow solid, mp
123–126°C. Trituration of this material with
1 : 1 ethyl acetate–petroleum ether (Note
16) gives
7.9–8.0 g (
61–62%) of
cis-1-methylcyclopentane-1,2-dicarboxylic acid as a white solid, mp
123–124.5°C (Notes
16-19).
2. Notes
1. All glassware was dried overnight in an
oven at 115°C and allowed to cool in a
desiccator.
2. A slight positive pressure of
nitrogen is maintained throughout the reaction.
3. A literature procedure
2 for the preparation of the zinc–copper couple was followed except for the use of slightly more (28%) than the indicated amount of
copper sulfate. The checkers found that the kind of
zinc used is critical.
Zinc dust, 325-mesh, from Aldrich Chemical Company, Inc. (catalog no. 20,998-8) gave
7,7-dichloro-1-methylbicyclo[3.2.0]heptan-6-one in
80–89% yield.
Zinc metal (dust) from Fisher Scientific Company (Lot 8744394) gave the dichloro ketone in yields of
37–61% (five trials). The Fisher
zinc was of unknown mesh, but was much more finely-divided than the Aldrich Chemical Company, Inc.
zinc.
7. This material was found to darken with time. Its spectral properties are the following: IR (film) cm
−1: 1805;
1H NMR (CDCl
3, 80 MHz) δ: 1.57 (s, 3 H), 1.5–2.5 (m, 6 H), 3.50 (m, 1 H). These values are in accord with those reported in the literature.
3
10. A
trap is used between the flask and the rotary evaporator as a precaution against possible bumping during the evaporation.
12. Should a noticeably exothermic reaction ensue, the cooling bath is replaced for a few minutes.
13. At this point the checkers filtered the mixture through a pad of 30 g of Celite to remove the green precipitate. This filtration reduces the problem of emulsions and clogging of the separatory funnel during subsequent extractions.
14.
Iodine formation becomes substantial at lower pH.
15. Normally 50–100 mL of this solution is required.
16. This is done first with 20 mL and then with 8 mL. Product loss is minimized by storing the trituration flask overnight at −25°C prior to removal of the supernatant solution. On evaporation, the supernatant solution affords an oil containing the diacid and a small amount of the corresponding anhydride. Treatment of this oil with
10% aqueous NaOH at room temperature overnight and then processing the solution as before yields an additional
0.4 g (
3%) of the diacid, mp
126–127°C.
17. The submitters report a crude yield of
11.5 g (
89%) and a recrystallized yield of
9.0 g (
70%), mp
128–129°C.
18. Melting points of
123–129°C have been reported for this compound.
5;
6;
7;
8;
9 Its spectral properties are the following: IR (Nujol) cm
−1: 2720, 2630, 1690;
1H NMR (CDCl
3, 80 MHz) δ: 1.44 (s, 3 H), 1.5–2.5 (m, 6 H), 2.72 (pseudo-t, 1 H,
J = 8), 10.8 (br s, 2 H).
19. Gas-chromatographic analysis (10%, Carbowax 20 M on 80–100 mesh Chromosorb W, 2.5 × 2 mm, column temperature 180°C, injection temperature 230°C, flow rate 10 mL/min, retention time 10 min) of the corresponding dimethyl ester, formed with ethereal diazomethane, indicated a purity of greater than 99%.
3. Discussion
This procedure serves to illustrate a relatively inexpensive, two-pot, stereoselective method for effecting vicinal dicarboxylation of alkenes that is more generally applicable and higher-yielding than the
palladium-catalyzed carbonylation reaction and other more circuitous procedures.
10 Part A of this procedure is a slight modification of the dichloroketene–olefin cycloaddition method previously described by Krepski and Hassner.
2 Part B makes use of Sharpless and co-workers'
ruthenium(III) chloride-catalyzed oxidation process
11 for the cleavage of the β-chloro enol acetate, which is formed on trapping the β-chloro enolate intermediate with
acetic anhydride. A slightly different, nonoptimized version of this procedure has been used
10,12 for the vicinal dicarboxylation of
1-decene,
cis- and trans-2-butene,
2-methyl-2-butene,
2,3-dimethyl-2-butene,
1-methyl-1-cyclohexene,
1,6-dimethyl-1-cyclohexene, and
5α-cholest-2-ene with overall yields of 52–83%.
cis-1-Methylcyclopentane-1,2-dicarboxylic acid has been previously prepared by a variety of methods: by oxidative cleavage (HNO
3) of
cyclobutanone5 and
cyclopentanone6 precursors, through saponification and oxidation (KMnO
4) of a
γ-butyrolactone intermediate,
7 and by anhydride formation and then hydrolysis starting from mixtures of the
cis- and
trans-diacids (obtained in about five steps).
8,9 Compared with these methods, the cycloaddition–cleavage procedure is much more efficient and practical. It requires only readily available reagents and easily affords, without any chromatographic separations, a product of high purity.
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