From Retrosynthesis to Robinson Annulation

Note Michael addition-aldol condensation with cyclization is an example of a tandem reaction, discovered by Nobel Prize laureate R. Robinson and named the Robinson annulation [26]. Tandem reactions are two or more reactions that occur in a defined order without the isolation of intermediates [27]. Robinson annulation affords mono-, bi- and tricyclic derivatives of cyclohexanone, important intermediates in many syntheses of natural products, in particular steroids. 

In the next examples, we shall practice retrosynthetic analysis of these strucmres. 

Example 4.13 Propose the retrosynthetic analysis and then synthesis of TM 4.10. 

On partial hydrogenation of resorcinol to 1,3-cyclohexanedione, C-methylation of enol is performed under standard conditions. In the next two steps, Robinson annelation is completed. Michael addition of methyl vinyl ketone affords an intermediate that spontaneously enters intramolecular aldol condensation to a stable six-membered ring in TM 4.10. 

The next retrosynthetic analysis illustrates the application of the concept of an activating group. 

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