Dienolates diastereoselective alkylation

A useful expansion of reductive alkylation strategies to include extended dienolates has been developed by Stork in the context of a Wichterle annula-tion [46, 47]. Dienone 30 was found to undergo regio- and diastereoselective alkylation to give the product resulting from a-alkylation of the less hindered enolate diastereoface (Scheme 3.4) [47]. The resulting dione 32 obtained after hydrolysis was utilized as a key intermediate in the total synthesis of adre-nosterone (33). 

Examples of alkylations of dienolates derived from a,/J-unsaturated ketones by base-catalyzed proton abstraction38 38" are shown for enolate 32. Here it is also evident that the presence of a 1,3-interaction greatly influences the diastereoselectivity. 

Dienolate alkylations have been applied successfully in syntheses of steroids and terpenoids. A highly diastereoselective application81 is the preparation of the phenanthrene derivative 35. 

As shown in Scheme 34, a rather profound solvent effect on dienolate alkylation diastereoselectivity has been noted for the steroidal enone (71). Such large solvent effects have not been documented for other systems. Possible explanations based upon the position of the transition state along the reaction coordinate and/or specific solvation of the dienolate have been advanced to account for preferential axial alkylation in benzene and equatorial alkylation in t-butyl alcohol.However, in view of the fact that the degree of aggregation of the dienolate as well as the structure of the aggregates may be modified considerably in going from one solvent to the other, rationalization of the results is difficult. 

Although there are only a few examples of alkylations of carboxylate enolates which are exocyclic to five-membered carbocyclic rings, the usual steric factors seem to control the stereoselectivity of these reactions. Thus, the dienolate (111) underwent reaction with 4-bromo-l-butene anti to the methoxymethyl substituents with high diastereoselectivity " and enolates derived from norbomane-2-carboxylates (112)... 

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