Reduction in Acyclic Systems

One of the first and most satisfactory methods of predicting the most favoured diastereoisomeric transition state for nucleophilic attack at acyclic aldehydes and ketones was proposed by Cram [12] and is based on the size of the substituents to the carbonyl. He considered that the preferred conformation from which reaction occurs has the largest adjacent group antiperiplanar to the carbonyl (Fig. 6-2), and the nucleophile attacks from the side with the smaller (S) group. 

When one of the substituents is a highly polar group (e.g. halogen) Cornforth [13] suggested that the polar group and oxygen atom stay as far apart as possible in order to minimise dipolar interactions for example reduction of 2-chloro-l-deu-tero-2,3,3-trimethylbutanal with lithium di-butoxy aluminium hydride is consistent with this model (Fig. 6-3) [14]. 

Because of the principle of microscopic reversibility it is appropriate to consider frontier orbital analysis of the reaction in either direction. The Hammond postulate dictates that the more exothermic the reaction the more the transition state will reflect the starting geometry, and frontier orbital analysis of reactant orbitals is expected to be a better predictor of relative transition state orbital interactions than for an endothermic or a less exothermic process. Conversely, frontier orbital analysis of product orbitals in exothermic reactions would be a poorer predictor of transition state energy. 

Interaction of the carbonyl 7r -orbital with an adjacent periplanar (T -orbital lowers the energy of the LUMO. This reduces the energy difference with the nucleophile HOMO (Fig. 6-6). The closer in energy that the is with an adjacent C-L fT -orbital the greater the lowering (A ) of the LUMO and the more favoured the reaction will be, i.e, the LUMO-HOMO separation becomes smaller. 

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The reduction of vinyl halides most often is carried out via a metallation-protonation reaction. For instance, sodium in ethanol was employed by Barton et a/. for the reduction of a steroidal vinyl iodide (Scheme 44). A number of conditions for vinyl halide reduction to alkenes have been reported, representative examples of which include vinyl chloride and bromide reduction in acyclic systems with... 

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