1,7-Octadien-3-one

[70855-06-0]  · C8H12O  · 1,7-Octadien-3-one  · (MW 124.20)

(used mainly as a bisannulation reagent to prepare two annulated six-membered rings)

Physical Data: colorless liquid, bp 38-42 °C/3 mmHg, 65 °C/20 mmHg; semicarbazone: mp 180-182 °C.

Solubility: sol most organic solvents.

Preparative Methods: prepared most conveniently by the palladium-catalyzed reaction of 1,3-Butadiene with Acetic Acid affording an equilibrium mixture (1:3) of 1-acetoxy-2,7-octadiene (2) and 3-acetoxy-1,7-octadiene (1) (eq 1);1,2 the lower-boiling (1) (90-95 °C/25 mmHg) can be separated from the higher-boiling (2) (103-108 °C/25 mmHg) by distillation. The desired allylic acetate (1) can also obtained by the palladium-catalyzed allylic rearrangement of the isomeric allylic acetate (2); hydrolysis of (1) affords 1,7-octadien-3-ol; this allylic alcohol is oxidized with Manganese Dioxide in CCl4, or with CrO3-pyridine in CH2Cl2, to afford the title reagent.

In another method, 1,7-octadien-3-ol is prepared in 80% yield by the reaction of Acrolein with the Grignard reagent prepared from 4-pentenyl bromide (eq 2); Jones oxidation of the alcohol affords 1,7-octadien-3-one in 89% yield.3

Handling, Storage, and Precautions: use in a fume hood.

Bisannulation.

1,7-Octadien-3-one can be regarded as a masked equivalent for 1-octene-3,7-dione, and can be used as a bisannulation reagent for the preparation of two annulated cyclohexene rings. The enone portion of the reagent is used for Michael and aldol reactions, while the terminal double bond serves as a masked methyl ketone which can be unmasked by Wacker-type oxidation with Palladium(II) Chloride-Copper(I) Chloride in aq DMF.4 A typical application is shown by the annulation of 2-methylcyclopentane-1,3-dione (eq 3).1 The first step involves Michael addition to the diketone, which is followed by aldol condensation to give the annulated cyclohexenone. The terminal double bond is then oxidized with catalytic PdCl2/CuCl, yielding the trione. The last step is aldol condensation to generate a new cyclohexenone ring.

(+)-19-Nortestosterone has been prepared from a CD ring intermediate by the bisannulation method using 1,7-octadien-3-one according to the sequence of reactions summarized in eq 4.1,5

Synthesis of a Trisannulation Reagent.

1,7-Octadien-3-one is converted to 7-acetoxydodeca-1,11-dien-3-one, used as a trisannulation reagent, by the sequence of reactions shown in eq 5.6 This compound is a masked equivalent for 1-dodecene-3,7,11-trione, with the C-7 and C-11 ketones masked as an acetoxy group and terminal double bond, which can be unmasked in a stepwise manner to generate the ketones.

A steroid synthesis based on the trisannulation is also carried out using the trisannulation reagent described above (eq 6).6


1. Tsuji, J.; Shimizu, I.; Suzuki, H.; Naito, Y. JACS 1979, 101, 5070.
2. (a) Takahashi, S.; Shibano, T.; Hagihara, N. TL 1967, 2451; BCJ 1968, 41, 454.
3. Oppolzer, W.; Bättig, K.; Hudlicky, T. T 1981, 37, 4359.
4. (a) Tsuji, J. S, 1984, 369; (b) Tsuji, J.; Shimizu, I.; Yamamoto, K. TL 1976, 2975.
5. Shimizu, I.; Naito, Y.; Tsuji, J. TL 1980, 21, 487.
6. Tsuji, J.; Kobayashi, Y.; Takahashi, T. TL 1980, 21, 483.

Jiro Tsuji

Okayama University of Science, Japan



Copyright 1995-2000 by John Wiley & Sons, Ltd. All rights reserved.