[57-57-8]  · C3H4O2  · b-Propiolactone  · (MW 72.07)

(three-carbon homologating electrophile for synthesis of carboxylic acids and b-hetero propionates; b-hydroxypropionylating reagent)

Physical Data: mp -33.4 °C; bp 162 °C; d 1.146 g cm-3.

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

Form Supplied in: colorless oil: widely available.

Preparative Methods: prepared by reaction of Ketene and Formaldehyde under the influence of a Friedel-Crafts catalyst,1,3 by ring-closure of b-halo propionic acids with base,4 or by dehydration of 3-hydroxypropionic acid with various condensation reagents.5

Handling, Storage, and Precautions: can be stored in the refrigerator for several months without noticeable changes; reacts with bacteriophage DNA causing inactivation, repair, and recombination.2 Owing to its carcinogenic property, b-propiolactone should be handled with due care.

General Discussion.

Although b-propiolactone (1) is prone to polymerization,6 it also readily undergoes ring opening with a variety of nucleophiles to give selectively alkylated products, in which two reaction pathways are involved (eq 1).1a

The addition to carbonyl carbon predominates to give a,b-unsaturated ketones or 1,4-diols (path A), when organolithium reagents,7 Grignard reagents,8 and (trifluoromethyl)trimethylsilane-fluoride anion9 are used as nucleophiles, while organocadmium reagents,7 enamines,10 thiols,11 and aminosilanes12 effect C-O bond fission to give propionic acid derivatives (path B). Studies using Group 14 organometallics such as Me3MNEt2 (M = Sn, Ge, Si) indicate that the regiochemistry of the ring opening is also dependent on the metal used.13 For example, the acyl-oxygen bond is cleaved by the tin reagent (path A), whereas the alkyl-oxygen bond is cleaved by the silicon and germanium reagents.

Organocopper reagents exhibit interesting regiochemistry in the ring opening of b-propiolactone. Selective b-attack is accomplished by the use of organocopper reagents.14 As shown in eq 2 and Table 1, organocuprate prepared from 2 equiv of Grignard reagent and 1 equiv of Copper(I) Iodide gives b-alkylated propionic acids in better yields than those prepared from the corresponding organolithium reagents. In the presence of a catalytic amount of a copper(I) salt, Grignard reagents open up the lactone ring at the b-carbon to the carbonyl in good yields.15 However, organolithium reagents, in the presence of catalytic amounts of copper(I) salts effect ring opening at the carbonyl carbon to give acylated products.7 The organocopper-phosphine complexes,16 prepared from organolithium reagents with Tri-n-butylphosphine and copper(I) iodide, attack selectively at the b-carbon.

The application of this three-carbon elongation reaction to the construction of naturally occurring products has been demonstrated in several examples. Dialkylcopper reagents prepared from Grignard reagents and copper(I) iodide react with acetylene to give the corresponding di-(Z)-1-alkenylcuprates (3), which in turn react with b-propiolactone to afford (Z)-4-alkenoic acids (4), in good yields with excellent (Z) selectivity (eq 3).17 (Z)-4-Heptenoic acid (4) (R = Et) serves as a useful starting material for syntheses of perfume and flavor components such as cis-jasmone (5), methyl jasmonate (6), and jasmolone (7) (eqs 4-6).18

Lactones possessing large-membered rings are prepared by ring opening of b-propiolactone. In the presence of a catalytic amount of a copper salt, o-alkoxy or metalloxy Grignard reagents react with b-propiolactone to give the corresponding homologated carboxylic acids, which can cyclize to form macrocyclic lactones (8) (eq 7)19 a,o-Di-Grignard reagents also serve as good chain elongation reagents for the synthesis of macrolides (9) (eq 8).20 b-Propiolactone is converted into the b-lactam (10) (eq 9) by ring opening with a nitrogen nucleophile and the products are used for the synthesis of b-lactam antibiotics.21

The ring opening of b-lactams with nitrogen nucleophiles is used for the synthesis of macrocyclic polyamine derivatives (11) (eq 10).22 The regiochemistry of the ring opening is dependent on the solvent; acetonitrile is the solvent of choice for N-alkylation.

An intriguing C-C bond fission occurs upon reaction of b-propiolactone with Potassium-18-Crown-6 or Potassium Naphthalenide to give acetates or their alkylated derivatives in good yield (eq 11). The potassium solution generated by contact of a potassium mirror with a solution of 18-crown-6 in THF at -20 °C effects the formation of enolate anion (12) derived from C-C bond cleavage. Upon treatment with Hydrochloric Acid or alkyl halides, the acetate (13) or its alkylated derivatives (14) are obtained, respectively.23 On the other hand, acrylic acid (15) is formed by the action of the potassium naphthalenide-18-crown-6 complex.24 Subsequent alkylation with alkyl halides gives the a,b-unsaturated esters (16).

b-Propiolactone readily interacts with transition metals such as platinum,25 cobalt, and rhodium to give ring-opened products, (eq 12) and, under an atmosphere of carbon monoxide, g-butyrolactone (17) is formed (eq 13).26

Related Reagents.

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

1. (a) Zaugg, H. E. OR 1954, 8, 305. (b) Fujisawa, T.; Sato, T. J. Synth. Org. Chem. Jpn. 1982, 40, 618 (CA 1982, 97, 198 011y). (c) Pommier, A.; Pons, J. M. S 1993, 441.
2. Fukuda, S.; Yamamoto, N. Cancer Res. 1970, 30, 830.
3. Noels, A. F.; Herman, J. J.; Teyssié, P. JOC 1976, 41, 2527.
4. Agostini, D. E.; Lando, J. B.; Shelton, J. R. J. Polym. Sci., A-1 1971, 9, 2775.
5. Mulzer, J.; Pointner, A.; Chucholowski, A.; Brüntrup, G. CC 1979, 52.
6. Roelens, S. CC 1990, 58; Gresham, T. L.; Jansen, J. E.; Shaver, F. W.; Gregory, J. T. JACS 1948, 70, 998.
7. Stuckwisch, C. G.; Bailey, J. V. JOC 1963, 28, 2362.
8. (a) Gresham, T. L.; Jansen, J. E.; Shaver, F. W.; Bankert, R. A. JACS 1949, 71, 2807. (b) Kutner, A.; Perlman, K. L.; Lago, A.; Sicinski, R. R.; Schnoes, H. K.; DeLuca, H. F. JOC 1988, 53, 3450.
9. Krishnamurti, R.; Bellew, D. R.; Prakash, G. K. S. JOC 1991, 56, 984.
10. Schroll, G.; Klemmemsen, P.; Lawesson, S.-O. JACS 1964, 18, 2201.
11. Trost, B. M.; Kunz, R. A. JOC 1974, 39, 2648; Ambrogi, V.; Grandolini, G.; Perioli, L.; Rossi, C. S 1992, 656; Gresham, T. L.; Jansen, J. E.; Shaver, F. W. JACS 1948, 70, 1001.
12. Taddei, M.; Tempesti, F. SC 1985, 15, 1019.
13. Itoh, K.; Kato, Y.; Ishii, Y. JOC 1969, 34, 459.
14. Fujisawa, T.; Sato, T.; Kawara, T.; Kawashima, M.; Shimizu, H.; Ito, Y. TL 1980, 21, 2181; Kawashima, M.; Sato, T.; Fujisawa, T. T 1989, 45, 403.
15. Sato, T.; Kawara, T.; Kawashima, M.; Fujisawa, T. CL 1980, 571; Normant, J. F.; Alexakis, A.; Cahiez, G. TL 1980, 21, 935.
16. Suzuki, M,; Suzuki, T.; Kawagishi, T.; Noyori, R. TL 1980, 21, 1247.
17. Fujisawa, T.; Sato, T.; Kawara, T.; Naruse, K. CL 1980, 1123; Alexakis, A.; Cahiez, G.; Normant, J. F. S 1979, 286.
18. Sato, T.; Kawara, T.; Sakata, K.; Fujisawa, T. BCJ 1981, 54, 505.
19. Fujisawa, T.; Mori, T.; Kawara, T.; Sato, T. CL 1982, 569; Sato, T.; Kawara, T.; Kokubu, Y.; Fujisawa, T. BCJ 1981, 54, 945.
20. Fujisawa, T.; Kawara, T.; Tago, H.; Sato, T. BCJ 1983, 56, 345.
21. Consterousse, G.; Teutsch, G. T 1986, 42, 2685.
22. Pratt, J. A. E.; Sutherland, I. O.; Newton, R. F. JCS(P1) 1988, 13.
23. Aye, K.-T.; Colpitts, D.; Ferguson, G.; Puddephatt, R. J. OM 1988, 7, 1454.
24. Jedlinski, Z.; Kowalczuk, M.; Misiolek, A. CC 1988, 1261.
25. Kowalczuk, M.; Kurcok, P.; Glówkowski, W.; Jedlinski, Z. JOC 1992, 57, 389.
26. Bitsi, G.; Kheradmand, H.; Jenner, G. JOM 1986, 310, 115.

Tamotsu Fujisawa & Makoto Shimizu

Mie University, Japan

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