Lithium 2,2,6,6-tetramethylpiperidide enolate formation

The E.Z ratio can be modified by the precise conditions for formation of the enolate. For example, the E.Z ratio for 3-pentanone and 2-methyl-3-pentanone can be increased by use of a 1 1 lithium tetramethylpiperidide(LiTMP)-LiBr mixture for... 

I-Alkynes from methyl ketones This reaction can be effected by conversion to Ihe enol phosphate followed by -elimination with LDA (equation I). In the case of a simple ketone such as 2-octanone the yield is low because of formation also of an allene. In such cases lithium tetramethylpiperidide is recommended as base. 

Lithium 2,2,6,6-tetramethylpiperidide (LITMP) was introduced by Olofson and Dougherty in 1973. This base appears to be significantly more hindered than LDA, and is useful for regioselective enolate formation in cases where a very bulky base is desirable. " Another very hindered base is lithium t-butyl-t-octylamide, introduced by Corey and Gross."... 

Alkynes are available from methyl ketones by elimination of the enol phosphate (eq 16). When the ketone contains o-branching, lithium tetramethylpiperidide has been recommended to circumvent allene formation. 

N-, and S-Acylations. 0-Ethoxycarbonylation is observed in some instances. Aliphatic alcohols, phenols, and cyanohydrins react in the presence of tertiary amines to give carbonates. Equatorial oriented steroid hydroxyls are selectively acylated in the presence of axial hydroxyl groups. Enol carbonates (eq 11 ) are readily derived from ketones by formation of the lithium enolate using Lithium 2,2,6,6-Tetramethylpiperidide in THF/HMPA at —78°C followed by an ethyl chloroformate quench at room temperature. The use of HMPA prevents competitive C-acylation. LiTMP is necessary to avoid side reactions com-... 

Control of Regioselectivity and Stereoselectivity. The recognition by Ireland and co-workers that Hexamethylphosphoric Triamide has a profound effect on the stereochemistry of lithium enolates has led to the examination of the effects of other additives, as the ability to control enolate stereochemistry is of utmost importance for the stereochemical outcome of aldol reactions. Kinetic deprotonation of 3-pentanone with Lithium 2,2,6,6-Tetramethylpiperidide at 0 C in THF containing varying amounts of HMPA or TMEDA was found to give predominantly the (Z)-enolate at a base ketone additive ratio of ca. 1 1 1, whereas with a base.ketone.additive ratio 1 0.25 1, formation of the ( )-enolate was favored (Table I). This remarkable result contrasts with those cases where HMPA base ratios were varied towards larger amounts of HMPA, which favored formation of the (Z)-enolate. ... 

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