[75697-62-0]  · C4H7LiO  · 1-Lithio-1-methoxycyclopropane  · (MW 78.05)

(synthesis of 2-vinylcyclobutanones,2 which are intermediates in the synthesis of higher-membered rings via ring expansion3)

Solubility: sol THF, in which solvent it is prepared.

Preparative Methods: from 1-methoxy-1-phenylthiocyclopropane4 via reductive lithiation with Lithium 4,4-Di-t-butylbiphenylide (LDBB) or Lithium 1-(Dimethylamino)naphthalenide (LDMAN) in THF at -78 °C.5 Alternatively, a similar reagent, 1-ethoxy-1-lithiocyclopropane, is obtained by lithium-tin and lithium-bromine exchange reactions of 1-ethoxy-1-(tri-n-butylstannyl)cyclopropane and 1-bromo-1-ethoxycyclopropane, respectively.6

Handling, Storage, and Precautions: presumed to be unstable and is used immediately for further transformations. a-Metalated ethers undergo Wittig rearrangement7 and/or carbenoid reactions.8

Reactions of 1-Lithio-1-methoxycyclopropane.

1-Lithio-1-methoxycyclopropane reacts at -78 °C with aldehydes to give the expected addition products in high yields (eq 1).9

(1-Methoxycyclopropyl)alkyl alcohols are usually not isolated and the crude reaction products are directly subjected to acid-catalyzed rearrangement to 2-substituted cyclobutanones (eq 2).

From a synthetic point of view, preparation of 2-vinylcyclobutanones is the most interesting application of the above procedure. Several different sets of conditions have been elaborated to accomplish the rearrangement of the intermediate secondary or tertiary cyclopropylalkyl alcohols. In most cases, a solution of 48% aqueous Tetrafluoroboric Acid in THF or ether was found to be most effective.2 Vinylcyclobutanones are prepared from a,b-unsaturated aldehydes and ketones (eqs 3 and 4).10

In the case of acid sensitive molecules, the rearrangement can be conducted under neutral conditions by using Trifluoromethanesulfonic Anhydride in the presence of a hindered base, 2,6-di-t-butyl-4-methylpyridine (eq 5).5

Synthetic Utility of 2-Vinylcyclobutanones.

2-Vinylcyclobutanones are important synthetic intermediates since they undergo ring expansion reactions under a variety of conditions. Thermal,5 acid catalyzed,3 alkoxide accelerated,11 or trimethylsilyl cyanide promoted12 rearrangements lead to the formation of five-, six-, and eight-membered ring systems.

Synthesis of 2-vinylcyclobutanones from 1-lithio-1-methoxycyclopropane rivals the method of Trost,13 which employs 1-lithio-1-phenylthiocyclopropane. In the latter method, substantial experimentation leading to different reaction conditions for each case is necessary to obtain good yields in the rearrangement step.4b

Related Reagents.

Cyclobutanones can also be prepared from 1-methylseleno-,14 1-phenylseleno-,14 and 1-bromocyclopropyllithium reagents15 (see 1-Bromo-1-lithio-2-phenylcyclopropane).

1. (a) Reissig, H-V. In The Chemistry of the Cyclopropyl Group Rappoport, Z., Ed.; Wiley: New York, 1987; pp 375-443. (b) Salaün, J. ibid., pp 809-878.
2. Cohen, T.; Matz, J. R. TL 1981, 22, 2455.
3. Matz, J. R.; Cohen, T. TL 1981, 22, 2459.
4. (a) Tanaka, K.; Uneme, H.; Matsui, S. CL 1980, 287. (b) Trost, B. M.; Keeley, D. E.; Arndt, H. C.; Rigby, J. H.; Bogdanowicz, M. J. JACS 1977, 99, 3080. (c) Braun, M.; Seebach, D. CB 1976, 109, 669.
5. Cohen, T.; Brockunier, L. T 1989, 45, 2917.
6. Gadwood, R. C.; Rubino, M. R.; Nagarajan, S. C.; Michel, S. T. JOC 1985, 50, 3255.
7. Nakai, T.; Mikami, K. CRV 1986, 86, 885.
8. (a) Kocienski, P.; Barber, C. PAC 1990, 62, 1933. (b) Boche, G.; Opel, A.; Marsch, M.; Harms, K.; Haller, F.; Lohrenz, J. C. W.; Thümler, C.; Koch, W. CB 1992, 125, 2265.
9. Cohen, T., Matz, J. R. JACS 1980, 102, 6900.
10. Lyle, T. A.; Mereyala, H. B.; Pascual, A.; Frei, B. HCA 1984, 88, 774.
11. Cohen, T.; Bhupathy, M.; Matz, J. R. JACS 1983, 105, 520.
12. Byers, J. B.; Spencer, T. A. TL 1985, 26, 713.
13. Trost, B. M. Top. Curr. Chem. 1986, 133, 3.
14. (a) Halazy, S.; Krief, A. CC 1979, 1136. (b) Halazy, S.; Krief, A. CC 1982, 1200. (c) Krief, A. Top. Curr. Chem. 1987, 135, 1.
15. Braun, M.; Seebach, D. AG(E) 1974, 13, 277.

Harry M. Walborsky & Marek Topolski

Florida State University, Tallahassee, FL, USA

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