Reactions of Enols and Enolate Anions

Reactions of Enols and Enolate Anions.—Several methods are described for transposition of an oxo-function to the adjacent site. They involve formation of a suitable a-substituted derivative (hydroxymethylene ° or benzylidene ) and subsequent steps which transform the substituent into an isolated oxo-group. Condensations leading to both the 2-hydroxymethylene- and the 2-arylidene-3-oxo-steroids are described for 3-ketones of the 5jS-series, and also of the 5j8,9j5,10a-( retro ) series.Condensations of aromatic aldehydes at C-2 in the 5 -series are unusually slow enolisation towards C-4 is preferred, but steric compression between C-4 and C-6 in 5/3-compounds severely hinders the condensation reaction at C-4, allowing reaction at C-2 via the 2-enol. Reduction of a 21-hydroxymethylene-pregnan-20-one (337) with sodium borohydride afforded the homopregnanediol (338), although reduction of enolised P-dicarbonyl compounds frequently proceeds via elimination to give enones, and thence allylic alcohols. 

The base-catalysed condensation of ethyl oxalate with steroid ketones, widely used in synthesis, has been exploited as an analytical method. The glyoxalyl derivative, obtained by careful acidification of the reaction mixture, exhibits u.v. absorption characteristic of the ketone (e.g. testosterone, 252 and 324 nm 17-ketone, 294nm 20-ketone, 290nm). 

Intramolecular condensation of 6a-esters, thioesters, or amides (339 X = O, S, or NH R = Me or Ph), under the enolising influence of sodium hydride, affords the novel 4,6-fused furano- (340), thiopheno- (341), and pyrrolo- (342) derivatives, respectively. The reactions comprise a Claisen-like condensation. 

Similar internal condensation of the 6-(3 -acetoxy-cis-prop-r-enyl)-4-en-3-one (343) gave the benzeno-steroid (344). A dehydrogenation step of uncertain nature is required here, following displacement of the acetoxy-group by attack of C-4. Another intramolecular cyclisation occurred when the 19(R)-acetoxy-19-methyl-3-ketone (345) was treated with base. The 2,19-oxido-derivatives (346) and (347) were obtained.  

Komeno, S. Ishihara, K. Takigawa, H. Itani, and H. Iwakura, Chem. and Pharm. 

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Phenols readily form new C-C bonds under a variety of conditions, again paralleling the reactions of enols and enolate anions. For example. 

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