Robinson annulation retrosynthetic analysis

Tran orm-based or long-range strategies The retrosynthetic analysis is directed toward the application of powerful synthesis transforms. Functional groups are introduced into the target compound in order to establish the retion of a certain goal transform (e.g., the transform for the Diels-Alder reaction, Robinson annulation, Birch reduction, halolactonization, etc.). 

For the puiposes of retrosynthetic analysis, a six-membered ring in a target can be related to a Robinson annulation of an existing ketone with an a,/3-unsamrated ketone. Normally cc,/3-unsaturated methyl ketones are used to facilitate the ring closure, but this is not an absolute requirement. Thus the target steroid S could potentially be constructed by a series of Robinson annulations as shown. The last retrosynthetic step (the first synthetic step) could be problematic as a mixture of regioisomers would be formed. 

Once you understand the mechanisms, concentrate on the synthetic applications of the process. Focus on the carbon-carbon bond-forming examples, with particular emphasis on the Michael addition, the 1,4-addition of enolates to enones or enals. The combination Michael addition-aldol condensation provides a powerful means of synthesis of six-membered rings, the Robinson annulation. Don t worry about all these people s names learn the retrosynthetic analysis for compounds containing six-membered rings. 

The Robinson annulation combines Michael addition to an a,/3-unsaturated ketone with intramoleeular aldol condensation (Section 18-11) to afford a cyclohexenone. Retrosynthetic analysis (Section 8-9) of the target molecule leads to the disconnection of two bonds in ring A the carbon-carhon double bond, by a retro-aldol condensation, and a single bond by a retro-Michael addition. The Rohinson annulation for the construction of ring A is closely related to the example in Section 18-11, which condenses 2-methylcyclohexanone with 3-buten-2-one. 

How would you synthesize each of the following, using the Robinson annulation Show both your retrosynthetic analysis and a forward reaction scheme, taking care to use enamines, activating and protecting groups as appropriate ... 

A Robinson annulation is comprised of a Michael reaction, followed by an intramolecular aldol condensation. To determine the starting materials necessary to prepare the desired product via a Robinson aimulation, we draw the following retrosynthetic analysis ... 

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