Reduction of o-B-unsaturated carbonyl compounds

The mechanism of the chemical reduction of enones with metal (Li, Na, etc.) in liquid ammonia can be described by the following equation in which the substrate 212 receives two electrons from the metal to give the dianion intermediate 213. This intermediate is then successively transformed into the enolate salt 214 and the ketone 215 with an appropriate proton donor source. It can readily be seen that the stereochemical outcome of this reaction depends on the stereochemistry of the protonation step 213 214. An excellent review on this topic has been recently written by Caine (60). This subject will be only briefly discussed here. 

In the reduction of octalone of the type IZ, the resulting enolate dianion 213 can adopt three different half-chair conformations 216, 217, and 218. Of these, only conformations 216 and 217 have the carbanion electron pair parallel to the i orbital of the enolate system allowing an electronic de- 

The above stereoelectronic arguments were proposed by Stork and Darling (61) to explain why the more stable isomer is not necessarily always obtained (62). For example, reduction of the octalone 221 with lithium-ammonia-ethanol followed by oxidation afforded the trans-2-decalone 222 even though the isomeric cis-2-decalone 223 is about 2 kcal/mol more stable than 222. Conformation 226 of the enolate dianion is the most favored sterically but it is electronically disfavored. Conformations and 2 are both electronically favored but 225 is less favored sterically than 224. Therefore. 

The reduction of 212 (R=H) gives a mixture of trans and cis decalones 219 and 220 (R=H) in a 99 1 ratio (63). An analysis of non-bonded interactions in the corresponding enolates 216 and 217 (R=H) indicates that the former should be favored only by about 1.0 kcal/mol, which should correspond to an approximately 80/20 trans/cis ratio. This result indicates that there is a significantly greater preference for the trans species 216 than would be predicted by analysis of non-bonded interactions. 

Other factors (charge repulsion, solvation factors, etc.) could influence the position of the equilibrium in favor of enolate dianion 216. It is also possible that there is a kinetic preference for the formation of dianion 216 and that this species would undergo protonation more rapidly than equilibration. This rule of axial protonation of 21 has been found to be widely applicable in many cases. However, in systems in which a significant amount of strain must be introduced in order for protonation to occur axially on 216, protonation of conformer 217. (and even conformer 218) becomes important (60). 

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