Lithium Phenylethynolate

[57015-19-7]  · C8H5LiO  · Lithium Phenylethynolate  · (MW 124.07)

(ambident nucleophile producing ketenes or alkynol esters in reactions with acid chlorides;1 intermediate reagent in carboxylic acid homologation;2 starting reagent in the synthesis of silyl ynol ethers3)

Physical Data: the pKa of phenylethynol is estimated to be less than 2.8.4

Solubility: THF; reacts with water and protic solvents.

Form Supplied in: prepared in situ and used directly.

Preparative Methods: four methods can be used for the preparation of lithium phenylethynolate and other lithium alkynolates: reaction of a,a-dibromo ketones with alkyllithium reagents (eq 1);1,2 a multistep, one-pot synthesis from ethyl esters (eq 2);2 reaction of isoxazole with n-Butyllithium (eq 3);5 and oxidation of lithium phenylacetylide by lithium t-butyl peroxide (eq 4).6 The first two reactions (eqs 1 and 2) are the most general and usually give the best results in the preparation of a variety of lithium alkynolates.2,3 The other two methods (eqs 3 and 4) lack generality and have only limited application. All these methods are used for the preparation of lithium alkynolates in situ; no attempts to isolate pure compounds have been reported.

Handling, Storage, and Precautions: must be prepared and handled under inert gas (Ar or N2) to exclude moisture. Solutions in THF are stable for several hours at room temperature.

Reactions with Acid Chlorides.

Lithium alkynolates are ambiphilic nucleophiles and can form products of both O- and C-attack in reactions with electrophilic reagents. Reaction of lithium alkynolates with dialkyl chlorophosphates affords alkynyl phosphate esters as the major products (eq 5). However, reactions with acyl chlorides under similar conditions results in both the alkynyl benzoate O-acylation product and the corresponding ketene due to C-acylation (eq 6).1

Reactions with Ketones and Aldehydes.

Carbon electrophiles such as ketones and aldehydes react with alkynolates, forming exclusively products of C-attack. Addition of phenylethynolate to cyclohexanone affords a spirolactone resulting from the cyclization of the originally formed ketene (eq 7). Similarly, the reaction of lithium alkynolates with benzaldehyde can be rationalized by the intermediate formation of ketene (eq 8); however, the final product in this case is the unsaturated acid, not a lactone.2a

Reactions with Alcohols.

Alcoholysis of lithium alkynolates yields esters (eq 9).2 This reaction is especially useful in organic synthesis as a method of ester homologation. In this case, ethyl esters of carboxylic acids are used for the generation of lithium alkynolates in situ (eq 2). Subsequent ethanolysis of lithium alkynolates in the presence of HCl gives homologated esters in good yield.2

Preparation of Silyl Ynol Ethers.

Silylation of lithium alkynolates with trialkylchlorosilanes can be used for the preparation of silyl ynol ethers.3 However, this method gives good yields only in reactions of sterically hindered alkynolates (eq 10).3c The analogous reaction of lithium alkynolates with trialkylgermanium and trialkyltin chlorides results in the exclusive formation of the corresponding ketenes.3a

1. Zhdankin, V. V.; Stang, P. J. TL 1993, 34, 1461.
2. (a) Kowalski, C. J.; Fields, K. W. JACS 1982, 104, 321. (b) Kowalski, C. J.; Haque, M. S.; Fields, K. W. JACS 1985, 107, 1429. (c) Kowalski, C. J.; Reddy, R. E. JOC 1992, 57, 7194. (d) Kowalski, C. J.; Lal, G. S. TL 1987, 28, 2463.
3. (a) Stang, P. J.; Roberts, K. A. JACS 1986, 108, 7125. (b) Kowalski, C. J.; Lal, G. S.; Haque, M. S. JACS 1986, 108, 7127. (c) Danheiser, R. L.; Nishida, A.; Savariar, S.; Trova, M. P. TL 1988, 29, 4917.
4. Kresge, A. J. ACR 1990, 23, 43.
5. Hoppe, I.; Schöllkopf, U. LA 1979, 219.
6. Julia, M.; Saint-Jalmes, V. P.; Verpeaux, J.-N. SL 1993, 233.

Viktor V. Zhdankin

University of Minnesota-Duluth, MN, USA

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