Disconnection at a Functional Group or Branch Point

Carbon-carbon bonds are frequently built by using carbonyl compounds. A carbonyl group normally confers a pattern of alternating potential electrophilic or nucleophilic reactivity along a carbon chain as shown in Structure 8.1 [4]. The electrophilic character exists in the 

Nucleophilic character exists in the derived enolate (8.3) or enol (8.4) form. The charges at these sites can be propagated through a conjugated 

K system and serve to attract another carbon reagent of opposite charge and give a new bond. 

If we consider a disconnection somewhere along the chain, we can decide whether the reactive site backed by the carbonyl group will be nucleophilic or electrophilic. Three different choices are taken in the following examples to illustrate the rationale. 

Which one of the three disconnections we select depends on other structural features of the particular product and on availability of materials. In the synthesis of 8.7, the other two disconnection choices would have required more steps and difunctional intermediate compounds because the compound is cychc. Compounds 8.5 and 8.6 could be made by any of the three methods. 

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The retrosynthesis of an alkane TM generally begins with an FGI that adds a functional group of your choice (an alkyl halide, alkene, alkyne, aldehyde, or ketone), and continues with a disconnection consistent with that functional group. Addition of the functional group at a branch point will likely lead to a good disconnection, but its precise location is not critical since it will ultimately be removed. 

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