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DOI:10.15227/orgsyn.068.0041

Organic Syntheses, Coll. Vol. 8, p.377 (1993); Vol. 68, p.41 (1990).

VICINAL DICARBOXYLATION OF AN ALKENE: cis-1METHYLCYCLOPENTANE-1,2-DICARBOXYLIC ACID
[1,2-Cyclopentanedicarboxylic acid, 1-methyl-, cis-(±)-]

Submitted by Jean-Pierre Deprés and Andrew E. Greene1.
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-1cyclopentene (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 (Note6) in 100 mL of anhydrous ether. Magnetic stirring is begun and the solution is added dropwise over 1hr 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 thenbriefly 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 overanhydrous 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 (0.2mm), nD20 1.4970 (Note 7).
B. cis-1-Methylcyclopentane-1,2-dicarboxylic acid. A 1-L, one-necked, round-bottomed flask (Note1) 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). Afterbeing stirred for 15 min with continued cooling, the reaction mixture is treated with 14.2 mL (150mmol) 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 solventand excess acetic anhydride are directly removed with a rotary evaporator at 25°C under water pumppressure (Note 10). The resulting solid residue is further dried for 15–30 min at 4 mm and thendissolved 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 (187mmol) 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 thickmixture 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 theaqueous phase is added 900 mL of 2 : 1 ether–ethyl acetate followed by a 2 N aqueous hydrochloric acidsolution until a pH of 2–3 is obtained (Note 14). After being vigorously agitated, the phases areseparated 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-1,2dicarboxylic 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 procedure2 for the preparation of the zinc–copper couple was followed except for the useof slightly more (28%) than the indicated amount of copper sulfate. The checkers found that the kind ofzinc 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). TheFisher zinc was of unknown mesh, but was much more finely-divided than the Aldrich Chemical
Company, Inc. zinc.
4. Ether and tetrahydrofuran were distilled from the sodium ketyl of benzophenone.
5. 1-Methyl-1-cyclopentene (96% pure) and trichloroacetyl chloride (99% pure) were purchased fromthe Aldrich Chemical Company, Inc. The trichloroacetyl chloride was distilled prior to use.
6. Phosphorus oxychloride (99% pure) was obtained from the Aldrich Chemical Company, Inc. anddistilled from potassium carbonate prior to use.
7. This material was found to darken with time. Its spectral properties are the following: IR (film) cm−1:1805; 1H NMR (CDCl3, 80 MHz) δ: 1.57 (s, 3 H), 1.5–2.5 (m, 6 H), 3.50 (m, 1 H). These values are inaccord with those reported in the literature.3
8. The solution of butyllithium in hexane was purchased from the Aldrich Chemical Company, Inc. andstandardized with menthol and phenanthroline4 before use.
9. Acetic anhydride was distilled prior to use.
10. A trap is used between the flask and the rotary evaporator as a precaution against possible bumping
during the evaporation.
11. Sodium periodate was obtained from the Aldrich Chemical Company, Inc. and ruthenium(III)chloride hydrate (5–10% water) was purchased from Fluka. The more expensive periodic acid canreplace sodium periodate; however, ruthenium(III) chloride appears to be somewhat more efficient thanruthenium(IV) oxide.
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 thetrituration flask overnight at −25°C prior to removal of the supernatant solution. On evaporation, thesupernatant 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 (CDCl3, 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 greaterthan 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 thanthe palladium-catalyzed carbonylation reaction and other more circuitous procedures.10 Part A of thisprocedure 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 process11 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 used10,12 for the vicinal dicarboxylation of 1-decene, cis- and trans-2butene, 2-methyl-2-butene, 2,3-dimethyl-2-butene, 1-methyl-1-cyclohexene, 1,6-dimethyl-1cyclohexene, 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 ofmethods: by oxidative cleavage (HNO3) of cyclobutanone5 and cyclopentanone6 precursors, throughsaponification and oxidation (KMnO4) of a γ-butyrolactone intermediate,7 and by anhydride formationand 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 andpractical. It requires only readily available reagents and easily affords, without any chromatographic
separations, a product of high purity.

References and Notes
1. Laboratoire d'Etudes Dynamiques et Structurales de la Sélectivité (LEDSS), Université Joseph
Fourier de Grenoble, Bât. 52 Chimie Recherche BP. 68, 38402 Saint Martin d'Hères Cedex,France. This work was supported by CNRS (UA 332).
2. Krepski, L. R.; Hassner, A. J. Org. Chem. 1978, 43, 2879–2882.
3. Jeffs, P. W.; Molina, G.; Cass, M. W.; Cortese, N. A. J. Org. Chem. 1982, 47, 3871–3875.
4. Watson, S. C.; Eastham, J. F. J. Organomet, Chem. 1967, 9, 165–168.
5. Wiberg, K. B.; Klein, G. W. Tetrahedron Lett. 1963, 1043–1045
6. Bagchi, P.; Banerjee, D. K. J. Indian. Chem Soc. 1947, 24, 12–14
7. Julia, M.; Salard, J. M.; Chottard, J. C. Bull. Soc. Chim. Fr. 1973, 2478–2482
8. Dutta, P. C. J. Indian. Chem. Soc. 1940, 17, 611–618
9. Bachmann, W. E.; Struve, W. S. J. Am. Chem. Soc. 1941, 63, 1262–1265.
10. See: Deprés, J.-P.; Coelho, F.; Greene, A. E. J. Org. Chem. 1985, 50, 1972–1973, and references
cited therein.
11. Carlsen, P. H. J.; Katsuki, T.; Martin, V. S.; Sharpless, K. B. J. Org. Chem. 1981, 46, 3936–3938.
12. Greene. A. E.; Deprés, J.-P.; Coelho, F.; Brocksom, T. J. J. Org. Chem. 1985, 50, 3943–3945.

Appendix
Chemical Abstracts Nomenclature (Collective Index Number);(Registry Number)petroleum ether
sodium ketyl of benzophenone
copper couple
1,2-Cyclopentanedicarboxylic acid, 1-methyl-, cis-(±)potassium carbonate (584-08-7)hydrochloric acid (7647-01-0)
ethyl acetate (141-78-6)
ether (60-29-7)
acetic anhydride (108-24-7)acetonitrile (75-05-8)
sodium hydroxide,
NaOH (1310-73-2)
sodium bicarbonate (144-55-8)
sodium chloride (7647-14-5)
sodium sulfate (7757-82-6)
carbon tetrachloride (56-23-5)
sodium thiosulfate (7772-98-7)
nitrogen (7727-37-9)
copper sulfate (7758-98-7)
iodine (7553-56-2)
Phosphorus Oxychloride (21295-50-1)
zinc,
Zinc metal (dust) (7440-66-6)
palladium (7440-05-3)
zinc chloride (7646-85-7)
Cyclopentanone (120-92-3)

γ-butyrolactone (96-48-0)
menthol (15356-60-2)
2,3-dimethyl-2-butene (563-79-1)
2-methyl-2-butene (513-35-9)butyllithium (109-72-8)
Tetrahydrofuran (109-99-9)
hexane (110-54-3)
periodic acid
1-methyl-1-cyclohexene
ruthenium(III) chloride (14898-67-0)
phenanthroline
Cyclobutanone (1191-95-3)
trichloroacetyl chloride (76-02-8)
Sodium periodate (7790-28-5)
cis- and trans-2-butene
1-decene (872-05-9)
1-methyl-1-cyclopentene
7,7-Dichloro-1-methylbicyclo[3.2.0]heptan-6-one (51284-43-6)
ruthenium(III) chloride hydrate (13815-94-6)
ruthenium(IV) oxide
1,6-dimethyl-1-cyclohexene
5α-cholest-2-ene
cis-1-Methylcyclopentane-1,2-dicarboxylic acid (70433-31-7)
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