Reduction of Ketones in Preference to Enones

Metal-ammonia solutions reduce conjugated enones to saturated ketones and reductively cleave a-acetoxy ketones i.e. ketol acetates) to the unsubstituted ketones. In both cases the actual reduction product is the enolate salt of a saturated ketone this salt resists further reduction. If an alcohol is present in the reaction mixture, the enolate salt protonates and the resulting ketone is reduced further to a saturated alcohol. Linearly or cross-conjugated dienones are reduced to enones in the absence of a proton donor other than ammonia. The Birch reduction of unsaturated ketones to saturated alcohols was first reported by Wilds and Nelson using lithium as the reducing agent. This metal has been used almost exclusively by subsequent workers for the reduction of both unsaturated and saturated ketones. Calcium has been preferred for the reductive cleavage of ketol acetates. 

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. 

Chamberlin and Reich investigated hydride additions to a,3-unsaturated ketones and the correlation of conformational preferences in enones with the ( )/(Z) stereoselectivity in formation of the corresponding enolates. They found that in acyclic systems s-trans enones gave enolates A and s-cis enones gave enolates B (Scheme 15). The reduction of a,3-unsaturated amides with L-selectride gave the same stereochemical results (Scheme 16). ... 

The configuration of enolates formed by the reduction has been correlated with the preferred ground-state conformation of the a,P-unsaturated carbonyl compound (Scheme 2.35). Thus, Chamberlin and Reich [129] noticed that, upon reduction with L-selectride, enone 113 adopting the s-trans conformation leads to the formation of enolate 114 in a highly stereoselective manner. On the other hand, the Birch reduction of ketone 115, which is kept by the... 

At first, the enone 23 was catalytically reduced to afford almost exclusively a cis fused ketone which was expected from the preceding examples. Birch reduction gave cis and trans products in a ratio of ca. 5 4 (13). In general six-membered ring ketones produce trans products preferentially under Birch reduction conditions. In this case the trans product was not the preferred product and the ratio did not change when several different conditions were tried. Thus Birch reduction followed by carboxylation with carbon dioxide of the enolate and methylation afforded the ester, whose ratio of the cis and trans products was ca. 

A study of the addition of dilithium carboxylates to acyclic enones under conditions of kinetic control has revealed that the reaction is irreversible and that the intrinsic preference for [1,2] addition may be completely changed to [1,4] when large groups are present on the acid or adjacent to the ketone group. The acid-catalysed decomposition of a-hydroperoxy-ketones to acids and ketones has been studied in detail in some cases, yields of acids can be excellent. 1,3-Dioxolans can be converted into the corresponding carboxylic acids by oxidative bromination followed by reduction with zinc under various conditions (Scheme 2). Readily available tetra-n-butylammonium permanganate (3) prom-... 

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