Acceptor synthons umpolung

The dissonant charge pattern for 2,5-hexanedione exhibits a positive (-1-) polarity at one of the a-carbons, as indicated in the acceptor synthon above. Thus, the a-carbon in this synthon requires an inversion of polarity Umpolung in German) from the negative (-) polarity normally associated with a ketone a-carbon. An appropriate substrate (SE) for the acceptor synthon is the electrophilic a-bromo ketone. It should be noted that an enolate ion might act as a base, resulting in deprotonation of an a-halo ketone, a reaction that could lead to the formation of an epoxy ketone Darzens condensation). To circumvent this problem, a weakly basic enamine is used instead of the enolate. 

In the case of 5-hydroxy-2-hexanone shown below, Umpolung of the polarity in the acceptor synthon is accomplished by using the electrophilic epoxide as the corresponding SE. 

You will perhaps realise from these particular examples that the d2 synthon will be represented in real life by an enolate or its equivalent and the a3 synthon by an a, 3-unsaturated carbonyl compound, both displaying the natural polarity of these fragments. It is generally true that even numbered donor synthons (d2, d4, etc.) and odd numbered acceptor synthons (a1, a3, etc.) have natural polarity while the odd numbered donor synthons (d1, d3, etc.) and the even numbered acceptor synthons (a2, a4, etc.) have unnatural polarity or umpolung. This makes the numbering of such synthons a useful quick check on the type of reagent likely to be needed. 

In the Seebach terminology cyclopropanes correspond to synthons having acceptor properties a and donor properties d respectively in a 1,3 distance, whereas the normal 1,2 relationship is valid for olefins. Many synthetic methods with umpolung use this... 

The synthetic value of homoenolates, in exact analogy to that of enolates, stems from their amphoteric nature (equations 1 and 2). In addition, homoenolates represent archetypal synthons in the concept of umpolung , acting as inverse polarity nucleophilic synthons of Michael acceptors. 

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