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DOI:10.15227/orgsyn.068.0175

Organic Syntheses, Coll. Vol. 8, p.43 (1993); Vol. 68, p.175 (1990).

INTRAMOLECULAR CYCLIZATION OF cis,cis-1,5CYCLOOCTADIENE USING HYPERVALENT IODINE: BICYCLO[3.3.0]OCTANE-2,6-DIONE[1,4-Pentalenedione, hexahydro-]

Submitted by Robert M. Moriarty1, Michael P. Duncan1, Radhe K. Vaid1, and OM Prakash2.
Checked by Deng Bing and Ekkehard Winterfeldt.

1. Procedure
A. 2,6-Diacetoxybicyclo[3.3.0]octane. (Compound 2; (Note 1) and (Note 2).) An ovendried. 1-L
round-bottomed flask, equipped with a magnetic stirring bar, a reflux condenser, and a drying tube(Drierite), is charged with iodosobenzene diacetate (IBD) (100 g. 0.31 mol) and 300 mL of glacialacetic acid. To this stirred mixture, 25 g (0.23 mol) of cis,cis-1,5-cyclooctadiene (COD) is added. The
resulting mixture is then heated to reflux for 16 hr (Note 3), at which time the colorless solution has
become brown-orange. At the end of this time the acetic acid is evaporated using a rotary evaporator (15mm). Reduced-pressure distillation (74–84°C at 0.060 mm) yields 29.1–30.5 g (56–58%) of 2.6diacetoxybicyclo[3.3.0]octane, as a pale-yellow liquid (lit.3 bp 84–88°C at 0.2 mm) (Note 4).
B. Bicyclo[3.3.0]octane-2,6-diol. (Compound 3; (Note 5).) An ice-cooled aqueous 10% solution ofsodium hydroxide (100 mL) is placed in a 250-mL, round-bottomed flask equipped with a magnetic
stirring bar and a stopper. To this ice-cooled solution 27.8 g of diacetate 2 (0.123 mol) is added
dropwise over a few minutes. The cooled solution is slowly allowed to warm to room temperature (1 hr)
and stirring is continued for 15 hr. at which time the colorless solution has become yellow-orange (Note6).
The reaction mixture is then extracted continuously with ether for a 3 days. After extraction theether is removed by rotary evaporation. The crude viscous liquid that results after evaporation (Note 7)
is distilled (Note 8) under reduced pressure (106–111°C at 0.06 mm) (lit.3 bp 90–96°C at 0.3 mm) toyield 14.5–16.2 g (83–93%) of 3, pure bicyclo[3.3.0]octane-2,6-diol, as a yellow viscous liquid (Note9).

C. Bicyclo[3.3.0]octane-2,6-dione. (Compound 4; (Note 10).) Diol 3, 12.6 g (0.089 mol), is placedin a 250-ml, three-necked, round-bottomed flask equipped with a mechanical stirrer and a reflux
condenser. Acetone (125 mL) is added and the mixture is cooled to 0°C. A 2.7 M solution of Jones
reagent (Note 11) (70 mL) is slowly added dropwise over 10 min at 0°C. The solution is allowed towarm slowly to room temperature (1 hr) and stirring is continued for an additional 15 hr.
After 15 hr the acetone is removed on a rotary evaporator and water (125 mL) is added. The darkgreen aqueous mixture is extracted continuously with ether for 3 days. The ether is removed by rotary
evaporation, which results in a yellow oil. The oil is then distilled under reduced pressure (74–79°C at0.06 mm) to yield analytically pure bicyclo[3.3.0]octane-2,6-dione, 4 (6.4–7.1 g, 52–58%) as a white
crystalline solid, mp 45–46°C (lit.4 mp 45.1–46.3°C) (Note 12) and (Note 13).

2. Notes
1. cis,cis-1,5-Cyclooctadiene (COD) and iodosobenzene diacetate (IBD) are purchased from Aldrich
Chemical Company, Inc.
2. The diacetate (2) is a mixture of three difficultly separable stereoisomers [the di-exo-diacetate (2a),di-endo-diacetate (2b), and the exo–endo-diacetate (2c)]. The major isomer is the di-exo-diacetate (2a)based on 13C-NMR of the known di-exo-diol (Note 9).

3. This solution of iodosobenzene, acetic acid, and cis,cis-1,5-cyclooctadiene should continue to be
stirred and should not be allowed to react for more than 20 hr (at refluxing temperature) to prevent
decomposition of the product diacetate.
4. The 1H NMR spectrum (CDCl3) is as follows δ: 1.60 (m, 8 H, CH2), 1.97 (s, 6 H, OAc), 2.55 (br, s, 2
H, CH), 4.90 (br, s, 2 H, CHOAc). The IR spectrum (neat) shows a carbonyl peak at 1738 cm−1.
5. This procedure for the preparation of the diol is an adapted version of that by Cantrell and Strasser.3 It
is a procedure superior to that of Crandall and Mayer.5
6. The checkers monitored the reaction by TLC using ethyl acetate as the developing solvent.
7. This viscous liquid (3) is easily transferred to a distilling flask by using acetone.
8. The use of a heat gun aids the distillation because the product is extremely viscous.
9. The 1H NMR spectrum (CDCl3) is as follows δ: 1.70 (m, 8 H, CH2), 2.61 (m, 2 H, CH), 3.05 (s, 2 H,OH), 3.90 (m, 2 H, CHOH). The IR spectrum shows a broad peak at 3500 cm−1. The major peaks in the13C NMR spectrum (CDCl ) are δ: 27.41 (C-4), 33.81 (C-3), 50.64 (C-1), 79.54 (C-2). The 13C NMR
3indicates that the major stereoisomer is 3a, the exo,exo-2,6-dihydroxy-cis-bicyclo[3.3.0]octane [lit.6 13C
NMR δ: 27.8 (C-4), 34.2 (C-3), 51.0 (C-1), 79.9 (C-2)].

10. Other oxidation procedures were used, including pyridinium chlorochromate (Corey's reagent),7 anddipyridine Cr(VI) oxide (Collins' reagent),8 but did not produce yields comparable to the Jones method.
11. Jones reagent was prepared by the method in Fieser and Fieser:9 Dissolve 13.36 g of chromium
trioxide in 11.5 mL of concd sulfuric acid, and carefully dilute this cooled solution (0°C) with water to
50 mL.
12. The 1H NMR spectrum (CDCl3) is as follows δ: 2.23 (m, 8 H, CH2), 3.00 (m, 2 H, CH). The IRspectrum (Nujol) shows a carbonyl peak at 1745 cm−1.
13. GLC analysis shows that the product is contaminated by small amounts of diol. If desired, purer
material could be obtained by sublimation at 35–40°C at 0.01 mm onto a cold finger kept at 0°C.4

3. Discussion
The preparation of bicyclo[3.3.0]octane-2,6-dione has been accomplished by intermolecular
reactions,4,10 intramolecular reactions,3,11 and degradation reactions.5,12
Bicyclo[3.3.0]octane-2,6-dione has been known since 1934,10 but extant procedures for large-scale
multigram synthesis of this versatile intermediate are cumbersome, except for the recently publishedresults of Hagedorn and Farnum.4 Whitesell and Matthews6 have shown that bicyclo[3.3.0]octanes arevaluable intermediates for the total synthesis of natural products.
We now report a simple, three-step synthesis of the dione, which uses simple procedures andinexpensive starting materials, to procure multigram amounts of bicyclo[3.3.0]octane-2,6-dione inreasonable yields.

References and Notes
Department of Chemistry, University of Illinois at Chicago, Chicago, IL 60607.
Department of Chemistry, Kurukshetra University, Kurukshetra (Haryana), India 132119.
Cantrell, T. S.; Strasser, B. L. J. Org. Chem. 1971, 36, 670.
Hagedorn, A. A., III; Farnum, D. G. J. Org. Chem. 1977, 42, 3765.
Crandall, J. K.; Mayer, C. F.; J. Am. Chem. Soc. 1967, 89, 4374.
Whitesell, J. K.; Matthews, R. S. J. Org. Chem. 1977, 42, 3878.
Corey, E. J.; Suggs, J. W. Tetrahedron Lett. 1975, 2647.
Collins, J. C.; Hess, W. W. Org. Synth., Coll. Vol. VI, 1988, 644.
Fieser, L. F.; Fieser, M. "Reagents for Organic Synthesis," Wiley: New York, 1967, Vol. 1, pp.
142–144.
10. Ruzicka, L.; Borges de Almeida, A.; Brack. A. Helv. Chim. Acta 1934, 17, 183.
11. Julia, M.; Colomer, E. An. Quim. 1971, 67, 199; Chem. Abstr. 1971, 75, 19766z.
12. McCabe, P. H.; Nelson, C. R. Tetrahedron Lett. 1978, 2819.
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9.

Appendix
Chemical Abstracts Nomenclature (Collective Index Number);(Registry Number)sulfuric acid (7664-93-9)
acetic acid (64-19-7)ethyl acetate (141-78-6)
ether (60-29-7)
sodium hydroxide (1310-73-2)
iodine (7553-56-2)
acetone (67-64-1)
chromium trioxide (1333-82-0)

Iodosobenzene diacetate (3240-34-4)
pyridinium chlorochromate (26299-14-9)
Bicyclo[3.3.0]octane-2,6-dione,
1,4-Pentalenedione, hexahydro- (77483-80-8)
2.6-diacetoxybicyclo[3.3.0]octane,
2,6-Diacetoxybicyclo[3.3.0]octane (17572-85-9)
Bicyclo[3.3.0]octane-2,6-diol (17572-86-0)
iodosobenzene, acetic acidcis,cis-1,5-cyclooctadiene
exo,exo-2,6-dihydroxy-cis-bicyclo[3.3.0]octane
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