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DOI:10.15227/orgsyn.067.0114

Organic Syntheses, Coll. Vol. 8, p.13 (1993); Vol. 67, p.114 (1989).

PALLADIUM(0)-CATALYZED syn-1,4-ADDITION OF
CARBOXYLIC ACIDS TO CYCLOPENTADIENE MONOEPOXIDE:
cis-3-ACETOXY-5-HYDROXYCYCLOPENT-1-ENE[4-Cyclopentene-1,3-diol, monoacetate, cis-]

Submitted by Donald R. Deardorff and David C. Myles1.
Checked by Helmut Grebe and Ekkehard Winterfeldt.

1. Procedure
An oven-dried, 300-mL, two-necked, round-bottomed flask is equipped with a Teflon-coatedmagnetic stirring bar, a pressure-equalizing dropping funnel, and a rubber septum with an 18-gauge
needle connected to a dry-nitrogen source. The nitrogen-flushed apparatus is charged with 125 mL of
dry tetrahydrofuran (Note 1) and 0.28 g (0.24 mmol, 0.2 mol%) of tetrakis(triphenylphosphine)
palladium(0) (Note 2). The mixture is stirred at room temperature until all of the palladium catalyst
dissolves (Note 3). The solution is cooled in an ice–water bath and 7.0 mL (7.3 g, 122 mmol) of acetic
acid (Note 4) is added via syringe. At this point a slight darkening of the solution is observed. A room
temperature solution containing 10.9 g of 92% cyclopentadiene monoepoxide (10.0 g, 122 mmol, (Note5)) in 40 mL of tetrahydrofuran is added over 10 min with the aid of the addition funnel. The original
pale-yellow color gives way to a deeper transparent orange. After 5 min (Note 6), the solution isconcentrated at ambient temperature under reduced pressure and the resulting reddish-brown oil ispassed through a plug of silica gel (50 g, (Note 7) with 450 mL of ethyl ether (Note 8). The slightly
cloudy filtrate is washed through a plug of anhydrous magnesium sulfate (60 g, 5 × 7-cm coarse glassfrit) with an additional 150 mL of ether (Note 9) The solvent is removed under reduced pressure to yielda pale-yellow oil. The material is distilled through a short-path apparatus at 73–75°C (0.15 mm) toafford 12.5–13.2 g (72–76%) of colorless oil that crystallizes upon refrigeration (mp 36–39°C) . The
material is homogeneous by TLC and 1H NMR (Note 10), but can be further purified byrecrystallization from an ether–hexane mixture to give colorless crystals, mp 38.5–41°C (Note 11).

2. Notes
1. Tetrahydrofuran was predried over potassium hydroxide Caution! See Org. Synth., Coll. Vol. V, 1973,
976 for possible hazard.), then dried by distillation from sodium/benzophenone ketyl under nitrogen.
2. Tetrakis(triphenylphosphine)palladium(0) was purchased from Aldrich Chemical Company, Inc., andused without further purification. No special precautions were taken in handling the catalyst.
3. Dissolution takes approximately 2–3 min.
4. Glacial acetic acid was purchased from J. T. Baker Chemical Company (Baker Analyzed Reagent)and distilled prior to use.
5. Cyclopentadiene monoepoxide was prepared from cyclopentadiene and peracetic acid according to
the well-established procedure of Korach et al.2 However, the submitters report that epoxidation ofcyclopentadiene under conditions developed by Knapp et al.3 for cyclohexadiene increased their isolated
yields from 40% to 62%. The major impurity in distilled cyclopentadiene monoepoxide is 3cyclopentenone. This by-product can be conveniently assayed by 1H NMR integration of the four
methylene protons that appear as a broad singlet at 2.80 δ. Epoxide purity can be determined by GLC
analysis on a 25 M Carbowax capillary column operated at 50°C.
6. TLC analysis using Baker Si250F precoated glass plates with a hexane–ethyl acetate (1 : 1) solvent
system indicates that all of the starting material is consumed.

7. Baker Analyzed Reagent silica gel 60–200 mesh was used in a 4.5 × 9.0-cm column. This step
removes most palladium-containing compounds from the reaction mixture. In order to ensure that thepalladium is efficiently separated, itis important that all tetrahydrofuran be removed from the crude oil
prior to filtration.
8. Anhydrous ether (purified) was purchased from J. T. Baker Chemical Company and used without
additional purification.
9. This step removes the final traces of palladium. It is imperative that all catalyst be removed prior todistillation since, on heating, this metal catalyzes the decomposition of cis-3-acetoxy-5hydroxycyclopent-1-ene into isomeric cyclopentenones and acetic acid.
10. cis-3-Acetoxy-5-hydroxycyclopent-1-ene has the following spectral characteristics: 1H NMR (200MHz, CDCl3) δ: 1.59 (dt, 1 H, J = 4.0 and 14.5, CH2), 2.00 (s, 3 H, CH3), 2.38 (br s, 1 H, OH), 2.76
(quintet, overlapping dt, 1 H, J = 7.4 and 14.5, CH2), 4.67 (m, 1 H, CHOH), 5.45 (m, 1 H, CHOAc),
5.92 (m, 1 H, CH=CH), 6.05 (m, 1 H, CH=CH); IR (neat) cm−1: 3410 (s), 1720 (s), 1250 (s).
11. 4-Acetoxy-2-cyclopentenone could be prepared in 85% yield by treatment of 1 equiv of this alcoholwith 1.1 equiv of pyridinium chlorochromate in methylene chloride for 1 hr at room temperature,
followed by washing with water, concentration, and distillation.

3. Discussion
Functionalized cyclopentenoids have been used extensively as key building blocks for the synthesisof many biologically active molecules.4 This procedure details the facile preparation of one suchversatile intermediate: cis-3-acetoxy-5-hydroxycyclopent-1-ene. Although important in its own right,
this material also serves as a one-step precursor to the highly useful synthetic substrate 4-acetoxy-2cyclopenten-1-one.4 Only the acetic acid adduct with cyclopentadiene monoepoxide is described here.
However, this palladium-catalyzed reaction appears to be general for other acidic substrates as well.5,6For example, the corresponding benzoate and phenyl ether adducts have been successfully prepared5
from both benzoic acid and phenol in yields of 87 and 82%, respectively. Moreover, the reaction is not
limited to just the monoprotected versions of cis-cyclopentene-3,5-diol. The corresponding diesters canbe similarly prepared by replacement of the carboxylic acid component with an anhydride. This minor
modification permits direct synthetic access to either the dibenzoate or diacetate in equally good yields(74 and 79%, respectively). Recently, silyl carboxylates and silyl phenoxides were also found to react
analogously with cyclopentadiene monoepoxide in the presence of Pd(0) catalyst.7 It should be stressedthat in each case only the cis-1,4-adducts are observed, despite the fact that three other stereoisomers arepossible. This remarkable stereo- and regiospecificity is undoubtedly a manifestation of an intermediate
palladium π-allyl complex.8
Racemic cis-monoesters of cyclopentene-3,5-diol were previously prepared by the selective
acylation9 10 11 of the meso-diol and the copper-mediated12 addition of carboxylic acid salts tocyclopentadiene monoepoxide. Optically active monoacetates can be accessed by enzymatichydrolysis13 14 15 16 17 of the corresponding diester. The present method offers four principal advantagesover the earlier reports: (1) it is operationally simple; (2) it requires a much shorter reaction time; (3) itgives better yields; and (4) it has widespread applicability, since reactants other than carboxylic acids
may be employed with equally good results.
A major disadvantage with the acylation method9,10,11 is that the starting material, cis-cyclopentene3,5-diol, is not readily available and must be prepared via photoxygenation procedures.18 Furthermore,
acylation occurs with the concomitant formation of diacylated product, which results in reduced yieldsand associated purification problems. The copper-mediated12 and palladium-catalyzed procedures sharesome similarities in that both use cyclopentadiene monoepoxide as their starting material and deliver thedesired product in good yield. But, unlike the palladium-catalyzed method, copper-mediated reactions
require two full equivalents of carboxylate salt, much lower reaction temperatures (−78°C), andsubstantially longer reaction times. Finally, the enantioselective hydrolysis13,14,15,16,17 of cis-3,5diacetoxycyclopent-1-ene by hydrolase enzymes is an effective two-step method for generating
optically enriched product.
This preparation is referenced from:

Org. Syn. Coll. Vol. 9, 132
Org. Syn. Coll. Vol. 9, 136z Org. Syn. Coll. Vol. 9, 487zz

References and Notes
1. Department of Chemistry, Occidental College, Los Angeles, CA 90041. This work wassupported by a Penta Corporation Grant of Research Corporation.
2. Korach, M.; Nielson, D. R.; Rideout, W. H. Org. Synth., Coll. Vol. V, 1973, 414–418.
3. Knapp, S.; Sabastian, M. J.; Ramanathan, H. J. Org. Chem. 1983, 24, 4786.
4. Harre, M.; Raddatz, P.; Walenta, R.; Winterfeldt, E. Angew. Chem., Int. Ed. Engl. 1982, 21, 480,
and references cited therein.
Deardorff,D. R.; Myles, D. C.; MacFerrin, K. D. Tetrahedron Lett. 1985, 26, 5615.
5.
Trost,B.
M.;
Angle, S. R. J. Am. Chem. Soc. 1985, 107, 6123, 7.
6.
7. Deardorff, D. R.; Shambayati, S.; Linde II, R. G.; Dunn, M. M. J. Org. Chem. 1988, 53, 189.
8. Keinan, E.; Roth, Z. J. Org. Chem. 1983, 48, 1769.
9. Tanaka, T.; Kurozumi, S.; Toru, T.; Miura, S.; Kobayashi, M.; Ishimoto, S. Tetrahedron 1976,32, 1713;
10. Trost, B. M.; McDougal, P. G. Tetrahedron Lett. 1982, 23, 5497;
11. Nara, M.; Terashima, S.; Yamada, S. Tetrahedron 1980, 36, 3161.
12. Marino, J. P.; Jaen, J. C. Tetrahedron Lett. 1983, 24, 441.
13. Deardorff, D. R.; Matthews, A. J.; McMeekin, D. S.; Craney, C. L. Tetrahedron Lett. 1986, 27,1255;
14. Laumen, K.; Reimerdes, E. H.; Schneider, M.; Gorisch, H. Tetrahedron Lett. 1985, 26, 407;
15. Laumen, K.; Schneider, M. Tetrahedron Lett. 1984, 25, 5875;
16. Wang, Y-F.; Chen, C-S.; Girdaukas, G.; Sih, C. J. J. Am. Chem. Soc. 1984, 106, 3695;
17. Miura, S.; Kurozumi, S.; Toru, T.; Tanaka, T.; Kobayashi, M.; Matsubara, S.; Ishimoto, S.
Tetrahedron 1976, 32, 1893.
18. Kaneko, C.; Sugimoto, A.; Tanaka, S. Synthesis 1984, 876.

Appendix
Chemical Abstracts Nomenclature (Collective Index Number);(Registry Number)silica gel
sodium/benzophenone ketyl
Racemic cis-monoesters of cyclopentene-3,5-diol
acetic acid (64-19-7)ethyl acetate (141-78-6)
ether,ethyl ether (60-29-7)
phenol (108-95-2)
nitrogen (7727-37-9)

Benzoic acid (65-85-0)
potassium hydroxide (1310-58-3)
palladium (7440-05-3)
methylene chloride (75-09-2)
magnesium sulfate (7487-88-9)
Tetrahydrofuran (109-99-9)
peracetic acid (79-21-0)
hexane (110-54-3)
CYCLOPENTADIENE (542-92-7)
cyclohexadiene (592-57-4)
pyridinium chlorochromate (26299-14-9)
CYCLOPENTADIENE MONOEPOXIDE
3-cyclopentenone4-Acetoxy-2-cyclopentenone,
4-Acetoxy-2-cyclopenten-1-one (768-48-9)
tetrakis(triphenylphosphine)palladium(0) (14221-01-3)
cis-3-Acetoxy-5-hydroxycyclopent-1-ene (60410-16-4)
cis-3,5-diacetoxycyclopent-1-ene (54664-61-8)
4-Cyclopentene-1,3-diol, monoacetate, cis- (60410-18-6)
cis-cyclopentene-3,5-diol
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