t-Butyl a-Lithioisobutyrate

(R = t-Bu)

[54191-20-7]  · C8H15LiO2  · t-Butyl a-Lithioisobutyrate  · (MW 150.15) (R = Me)

[35717-10-3]  · C5H9LiO2  · Methyl a-Lithioisobutyrate  · (MW 108.07) (R = Et)

[53807-80-0]  · C6H11LiO2  · Ethyl a-Lithioisobutyrate  · (MW 122.09)

(relatively stable ester enolates)

Physical Data: white solids. The X-ray crystal structure of the TMEDA complex (R = t-Bu) has been obtained.1 The IR and 1H, 13C, and 7Li NMR spectra for amine-free reagents have been reported.2,3

Solubility: sol THF; insol hexane and benzene (R = Me, t-Bu); the ethyl enolate (R = Et) is moderately sol benzene.4

Preparative Methods: for most transformations, a THF solution prepared by addition of the appropriate isobutyric ester to 1 equiv (or slight excess) of Lithium Diisopropylamide in THF at -78 °C is used directly. Solid reagents are prepared by addition of slightly less than 1 equiv of the ester (diluted 1:1 in toluene or benzene) to a 0.4 M solution of LDA in the same solvent at 10 °C. The precipitate is isolated by centrifugation and dried for at least 5 h at 1 mm (65% yield).3

Handling, Storage, and Precautions: the reagents react with air and moisture. Solutions of the amine-free reagents in THF slowly form b-keto esters with a half-life of 4200 min at 25 °C (R = Et).4 The solid reagents are stable indefinitely at 25 °C.

Reactions.

The esters of isobutyric acid form relatively stable lithium enolates. Transformations of these enolates often occur in high yield, in part due to their greater stability and also because steric hindrance slows subsequent side reactions of the product.

Acylation with aroyl chlorides affords a,a-dimethyl b-keto esters which may be hydrolyzed and decarboxylated to isobutyrophenones.5 Arylation of this stable enolate may be accomplished by reaction with arenechromium tricarbonyl complexes (e.g. anisole) and subsequent iodination (eq 1).6 Vinylation may be effected by Nickel(II) Bromide catalysis.7

For other applications of these ester enolates, see the entry for Ethyl Lithioacetate.

Related Reagents.

t-Butyl a-Lithiobis(trimethylsilyl)acetate; Dilithioacetate; Ethyl Bromozincacetate; Ethyl Lithioacetate; Ethyl Lithio(trimethylsilyl)acetate.


1. Seebach, D.; Amstutz, R.; Laube, T.; Schweizer, W. B.; Dunitz, J. D. JACS 1985, 107, 5403.
2. (a) Vancea, L.; Bywater, S. Macromolecules 1981, 14, 1321. (b) Wang, J. S.; Jérome, R.; Warin, R.; Teyssié, P. H. Macromolecules 1993, 26, 1402.
3. Lochmann, L.; Lim, D. JOM 1973, 50, 9.
4. Lochmann, L.; Trekoval, J. JOM 1975, 99, 329.
5. Logue, M. W. JOC 1974, 39, 3455.
6. (a) Semmelhack, M. F.; Clark, G. JACS 1977, 99, 1675. (b) Semmelhack, M. F.; Clark, G. R.; Garcia, J. L.; Harrison, J. J.; Thebtaranonth, Y.; Wulff, W.; Yamashita, A. T 1981, 37, 3957.
7. Millard, A. A.; Rathke, M. W. JACS 1977, 99, 4833.

Michael Rathke & Robert Elghanian

Michigan State University, East Lansing, MI, USA



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