Steroid enones, protonated, reduction

Protonation of the a-carbanion (50), which is formed both in the reduction of enones and ketol acetates, probably first affords the neutral enol and is followed by its ketonization. Zimmerman has discussed the stereochemistry of the ketonization of enols and has shown that in eertain cases steric factors may lead to kinetically controlled formation of the thermodynamically less stable ketone isomer. Steroidal unsaturated ketones and ketol acetates that could form epimeric products at the a-carbon atom appear to yield the thermodynamically stable isomers. In most of the cases reported, however, equilibration might have occurred during isolation of the products so that definitive conclusions are not possible. 

The use of enamines as protective groups seems largely to be confined to steroid chemistry, where they serve (in their protonated form) to protect the A-B enone system from bromination and reduction. A large body of literature exists on the preparation and chemistry of enamines, which are easily hydrolyzed with water or aqueous acid. 

Selective catalytic hydrogenation of the 6,7-double bond of 17/3-acetoxy-7-methylandrosta-4,6-dien-3-one was achieved with Pd-C-PhCH20H and gave the 7/8-methyl dihydro-compound. Added FeCls has been reported to improve the selectivity of reduction of a,/S-enones in metal-ammonia reactions, thereby improving the yield of the saturated ketones. Similar improvements were observed in the lithium-ethylamine reductions at -78 C when a substantial excess of lithium was used and t-butyl alcohol was the proton source. The influence of solvent and added nitrogenous bases on the stereoselectivity of hydrogenation of A - and A -3-oxo-steroids with Pd catalysts has been studied, and the stereoselectivity of Pd-catalysed hydrogenation of various A -7-oxo-steroids has been reported to be unaffected by substituents at C-3 or C-17. 

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