(R = CH&tbond;C-)

[59092-51-2]  · C5H4O2  · b-Ethynyl-b-propiolactone  · (MW 96.09) (R = CH2=CH-)

[7379-79-0]  · C5H6O2  · b-Vinyl-b-propiolactone  · (MW 98.11)

(five-carbon homologating reagents for synthesis of dienoic and enoic acid derivatives)

Physical Data: R = ethynyl, bp 34-36 °C/3 mmHg; R = vinyl, bp 44-48 °C/4 mmHg.

Solubility: miscible with alcohol, acetone, ether, chloroform.

Form Supplied in: colorless oil.

Preparative Methods: by [2 + 2] cycloaddition of ketene with propynal (for b-ethynyl-b-propiolactone)2a and with acrolein (for the b-vinyl analog).2b,c

Handling, Storage, and Precautions: can be stored in the refrigerator for several months without noticeable changes. Cancer suspect reagent; b-ethynyl- and b-vinyl-b-propiolactone should be handled with due care.


Studies on the ring opening of b-ethynyl-b-propiolactone indicate that, under the influence of a catalytic amount of Palladium(II) Chloride in methanol or ethanol at room temperature, the ring opening takes place smoothly to give 3-alkoxy-4-pentynoic acids (eq 1).2a When the crude mixture is refluxed for a few hours, a quantitative esterification takes place.

Regioselective attack at the terminal sp carbon is accomplished by the use of Grignard reagents in the presence of Copper(I) Iodide to give 3,4-alkadienoic acids (eq 2).3 Results using a variety of Grignard reagents are summarized in Table 1. In the case of allylic metal reagents, diallylcuprate appears to be the reagent of choice.

The application of this procedure to the synthesis of pellitorine is accomplished by the use of this ring opening followed by isomerization of the allenic double bond and amide formation (eq 3).4


The regioselectivity of the ring opening of the vinyl analog is dependent on the nucleophile used (eq 4). Sodium Methoxide, a hard nucleophile, effects acyl-oxygen cleavage (path A), whereas methanol and benzylamine attack at the b-carbon to the carbonyl (path B), and a soft nucleophile such as Lithium Iodide or organocopper reagents favor path C.5 In the case of organocopper reagents, the geometry of the resulting double bonds is (E) when the reaction is conducted at lower temperatures. Similar to the reaction with the b-ethynyl derivative, diallylcuprate seems to be a better reagent for allylation.5,6 In addition to Grignard reagents, the regioselective ring opening proceeds with metalated N,N-dimethylhydrazone (2), an enolate equivalent, to give 7-oxo-3-alkenic acid,7 whereas lithium dithioester enolate (3) effects the formation of 6-(methylthio)thiocarbonyl-(E)-3-alkenoic acid.8

Under the influence of a catalytic amount of PdCl2 in methanol or ethanol at room temperature, the b-vinyl derivative also undergoes ring opening smoothly to give 3-alkoxy-4-pentenoic acids (eq 5).2a

The reaction with 9-Borabicyclo[3.3.1]nonane (9-BBN) followed by sodium methoxide gives cyclopropylacetic acid (eq 6).9

b-Vinyl-b-propiolactone serves as a useful C5 unit for the syntheses of royal jelly acid (4), queen substance (5),10 recifeiolide (6), and pyrenophorin (7).11

Related Reagents.

N-Benzyloxycarbonyl-L-serine b-Lactone; a,b-Butenolide; g-Butyrolactone; Dihydro-5-(hydroxymethyl)-2(3H)-furanone; b-Methyl-b-propiolactone; b-Propiolactone.

1. (a) Fujisawa, T.; Sato, T. J. Synth. Org. Chem. Jpn. 1982, 40, 618 (CA 1982, 97, 198 011y). (b) Pommier, A.; Pons, J. M. S 1993, 441.
2. (a) Noels, A. F.; Herman, J. J.; Teyssie, P. JOC 1976, 41, 2527. (b) McCain, J. H.; Marcus, E. JOC 1970, 35, 2414. (c) White, E. R. In Acrolein; Smith, C. W., Ed.; Wiley: New York, 1962; p 142.
3. Sato, T.; Kawashima, M.; Fujisawa, T. TL 1981, 22, 2375.
4. Fujisawa, T.; Okada, N.; Takeuchi, M.; Sato, T. CL 1983, 1271.
5. Fujisawa, T.; Sato, T.; Takeuchi, M. CL 1982, 71.
6. (a) Sato, T.; Takeuchi, M.; Itoh, T.; Kawashima, M.; Fujisawa, T. TL 1981, 22, 1817. (b) Kawashima, M.; Sato, T.; Fujisawa, T. BCJ 1988, 61, 3255.
7. Fujisawa, T.; Takeuchi, M.; Sato, T. CL 1982, 1521.
8. Fujisawa, T.; Itoh, T.; Sato, T. CL 1983, 1901.
9. Kawashima, M.; Fujisawa, T. CL 1983, 1273.
10. Fujisawa, T.; Sato, T.; Itoh, T. CL 1982, 219.
11. Fujisawa, T.; Takeuchi, M.; Sato, T. CL 1982, 1795.

Tamotsu Fujisawa & Makoto Shimizu

Mie University, Japan

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