Functional Group-Keyed Skeletal Disconnections

The category of 2-Gp-keyed transforms which disconnect C-C bonds is among the most important of all transform types. These transforms, especially in their stereoselective versions, are workhorses of retrosynthetic planning as their names alone attest aldol, Michael, Claisen, 

A simple example of this use of 2-Gp disconnections is shown for 159. In this illustration 

With strategic bond guidance, it is easy to find 2-Gp transform disconnections even if neither FG of an effective retron is present. In the case of the bridged aldehyde 160, recognition of the strategic bond shown (in bold face) keys FGI processes in both directions from the bond, which successfully establish the aldol retron leading to molecular disconnection by a sequence of aldol and Michael transforms, to generate a simple chiral precursor.31 

Not infrequently, when multiple FGI transforms must be used to establish the retron for a disconnective transform, as in the illustration shown just above, there may be alternative orderings of the FGI steps. Although the optimum ordering generally must be determined for each individual situation, it generally is dictated by considerations of topology, stereochemistry. 

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