Vinylcyclopropanation of enones in [2+3] cyclopentene annulation: application to the total synthesis of (-)-retigeranic acid

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Virginia Polytechnic Institute and State University


The addition of the Iithium dienolate 161a derived from ethyl 2-bromocrotonate (163) to several enones provided vinylcyclopropanes of type 165 which were converted by thermolysis to the corresponding cyclopentenes in an overall [2+3] annulation process.

[see document for diagram of chemical compounds]

The reactions of 161a with other electrophiles such as ketones, α,ß-unsaturated esters and α,ß-unsaturated aldehydes were also investigated. The possibility of asymmetric induction utilizing (-)-menthyl 2-bromocrotonate (169) was briefly investigated.

An application of this methodology was expressed in the total synthesis of (-)- retigeranic acid (1), achieved in fifteen steps from menthene (187) in a convergent and enantioselective fashion. The key steps in this synthesis involved the vinylcyclopropanation of bicyclic enone 144 with the lithium dienolate of bromide 180, to provide vinylcyclopropanes 179 and, through their thermolytic rearrangement, the pentacyclic ketone 178, which was converted to the title compound.

[see document for diagram of chemical compounds]