[3002-94-6]  · C3H5Li  · Cyclopropyllithium  · (MW 48.02)

(organolithium reagent used in the synthesis of a variety of cyclopropyl derivatives,2 five-membered ring nitrogen heterocycles via cyclopropylimine rearrangement,3 and cyclopentenes via vinylcyclopropane rearrangement4)

Alternate Name: lithiocyclopropane.

Solubility: sol pentane and ether.

Form Supplied in: solution in pentane or ether.

Analysis of Reagent Purity: cyclopropyllithium solutions should be titrated before use by one of the standard titration methods,5 e.g. Gilman's double titration.6

Preparative Methods: cyclopropyllithium is usually prepared as a solution in ether by reacting highly dispersed Lithium with cyclopropyl chloride7 or bromide.8 The reaction can also be conducted in pentane.2 Transmetalation methods have also been described.7b,9

Handling, Storage, and Precautions: solutions of organolithium reagents are highly flammable and moisture sensitive. Appropriate precautions are recommended. Use in a fume hood. Stability of cyclopropyllithium in ether is similar to that of n-Butyllithium, whereas in THF its stability is greater.8a

Synthesis of Cyclopropyl Derivatives.

Cyclopropyllithium reacts readily with common electrophiles to form a variety of compounds containing a cyclopropyl group. Thus reaction with aldehydes10 and ketones2,11 leads to secondary and tertiary alcohols respectively (eqs 1 and 2).11a

Two- and three-carbon homologations have been realized by using ethylene oxide7a and oxetane8b as electrophiles. Reaction with vinyl-substituted epoxides (eq 3) constitutes an example of four-carbon homologation.12

Cyclopropyllithium condenses in a typical fashion with carboxylic acids to give cyclopropyl ketones,13 and a controlled reaction with N-Formylpiperidine leads to cyclopropylcarbaldehyde in 75% yield.14 Cyclopropyllithium also adds to carbon-nitrogen multiple bonds. Thus addition to imines leads to amines15 while reaction with cyanopyridines yields ketones in good yields (eq 4).16

Cyclopropyllithium has also been used in the synthesis of cyclopropylpyridines,12 Cyclopropyltriphenylphosphonium Bromide,18 cyclopropyl phosphines,19 silanes19,20 and organogermanium compounds.21

Synthesis of Five-Membered Ring Nitrogen Heterocycles.

Addition of cyclopropyllithium to a-piperidinocyclopropanenitriles leads to the intermediate imines which subsequently undergo acid catalyzed rearrangement to form nitrogen heterocycles in moderate yields. Different products can be obtained depending on the kind of acid used (eq 5).3,22

Synthesis of Cyclopentenes via Thermal Rearrangement of Vinylcyclopropanes.

A mixed cuprate prepared in situ from cyclopropyllithium and PhSCu readily displaces iodide in b-iodocyclopentenones to give the substitution products in high yields. The latter undergo thermal ring expansion, providing an interesting method for cyclopentene annulation (eq 6).4

Related Reagents.

Cis and trans 1-lithio-2-methoxycyclopropanes (1) were prepared by lithium-halogen exchange reaction from corresponding bromides and condensed with aldehydes to give the addition products which readily undergo acid-catalyzed rearrangement to b,g-unsaturated aldehydes.23

Both 1-lithio-1-methyl-2-vinylcyclopropanes (2) and 1-lithio-2-vinylcyclopropanes (3) (cis and trans) were prepared in similar fashion and subsequently applied to cycloheptane annulations.24,25 These and other substituted cyclopropyllithium reagents are configurationally stable.26

See also 1-Bromo-1-lithio-2-phenylcyclopropane; Cyclopropylmagnesium Bromide; 1-Lithio-1-methoxycyclopropane; Lithium Cyclopropyl(phenylthio)cuprate.

1. (a) Wakefield, B. J. The Chemistry of Organolithium Compounds; Pergamon: Oxford, 1974. (b) Schöllkopf, U. MOC 1970, XIII/1, 87. (c) Boche, G.; Walborsky, H. M. In The Chemistry of the Cyclopropyl Group, Rappoport, Z., Ed; Wiley: Chichester, 1987; Chapter 12. (d) Boche, G.; Walborsky, H. M. Cyclopropane Derived Reactive Intermediates, Wiley: Chichester, 1990.
2. Hart, M.; Sandri, J. M. CI(L) 1956, 1014.
3. Wasserman, H. H.; Dion, R. P. TL 1982, 23, 1413.
4. Piers, E.; Banville, J.; Lau, C. K.; Nagakura, I. CJC 1982, 60, 2965.
5. (a) Crompton, T. R.; Comprehensive Organometallic Analysis, Plenum: New York, 1987; pp 181-192. (b) Schöllkopf, U. MOC 1970, XIII/1, 3.
6. Gilman, H.; Haubein, A. H. JACS 1944, 66, 1515.
7. (a) Hart, H.; Cipriani, R. A. JACS 1962, 84, 3697. (b) Applequist, D. E.; O'Brien, D. E. JACS 1963, 85, 743.
8. (a) Seyferth, D.; Cohen, H. M. JOM 1963, 1, 15. (b) Wagner, P. J.; Liu, K. C.; Noguchi, Y. JACS 1981, 103, 3837.
9. Seyferth, D.; Cohen, H. M. IC 1963, 2, 625.
10. Heidt, P. C.; Bergmeier, S. C.; Pearson, W. H. TL 1990, 31, 5441.
11. (a) Okazawa, N.; Sorensen, T. S. CJC 1978, 56, 2355. (b) Shimasaki, M.; Hara, H.; Suzuki, K. TL 1989, 30, 5443.
12. Tamura, M.; Suzukamo, G. TL 1981, 22, 577.
13. Masamune, S.; Kaiho, T.; Garvey, D. S. JACS 1982, 104, 5521.
14. Olah, G.; Arvanaghi, M. AG(E) 1981, 20, 878.
15. Cainelli, G.; Giacomini, D.; Mezzina, E.; Panunzio, M.; Zarantonello, P. TL 1991, 32, 2967.
16. Edward, W. B. III JHC 1975, 12, 413.
17. Walter, K. CB 1975, 108, 3415.
18. (a) Longone, D. T.; Doyle, R. R. CC 1967, 300. (b) Schier, A.; Schmidbaur, H. CB 1984, 117, 2314.
19. Schmidbaur, H.; Schier, A. S 1983, 372.
20. Dakkouri, M.; Kehrer, H.; Buhmann, P. CB 1979, 112, 3523.
21. Dakkouri, M.; Kehrer, H. CB 1983, 116, 2041.
22. Wassermann, H. H.; Dion, R. P.; Fukuyama, J. M. H 1989, 28, 629.
23. Corey, E. J.; Ulrich, P. TL 1975, 3685.
24. Wender, P. A.; Eissenstat, M. A.; Filosa, M. P. JACS 1979, 101, 2196.
25. (a) Wender, P. A.; Filosa, M. P. JOC 1976, 41, 3490. (b) Marino, J. P.; Browne, L. J. TL 1976, 3245. (c) Piers, E.; Lau, C. K.; Nagakura, I. TL 1976, 3233. (d) Piers, E.; Nagakura, I. TL 1976, 3237.
26. Applequist, D. E.; Peterson, A. H. JCS 1961, 83, 862. Walborsky, H. M.; Impastato, F. J.; Young, A. E.; JACS 1964, 86, 3283. Corey, E. J.; Eckrich, T. M. TL 1984, 25, 2415.

Harry M. Walborsky & Marek Topolski

Florida State University, Tallahassee, FL, USA

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