Synthesis of TMs with a 1,6-Dicarbonyl Pattern

Deprotonation, followed by alkylation with ethyl bromoacetate, provides the required carbon framework. Hydrolysis of both esters, followed by decarboxylation of the P-keto acid moiety, removes the activating group. The resulting carboxyhc acid must be reesterified to give the desired TM. 

Transformation b converts the cyclohexanone alpha carbon to an electrophile by brominating that position. An Sn2 with the stabilized diethyl malonate anion add the required two-carbon chain. As in a, the synthesis of the TM concludes with hydrolysis of the diester, decarboxylation, and reesterification. 

Since attempting to disconnect a 1,6-dicarbonyl leads to illogical synthons, a retrosynthesis involving a functional group interconversion should be considered instead. 

Since ozonolysis of a cyclohexene affords 1,6-dicarbonyls, this would be an effective approach to such target molecules. Use of reductive or oxidative workups can give rise to various combinations of aldehydes, ketones, and carboxylic acids. 

One possible retrosynthesis of a 1,6-dicarbonyl involves a functional group interconversion to a cyclohexene. The cyclohexene derivative can be prepared in a variety of ways (e.g., by a Diels-Alder reaction), so the retrosynthesis can continue from there. The synthesis of target molecules containing six-membered rings will be discussed in a later section. 

---