Synthesis of polyquinane natural products using the tandem radical cyclizations of aziridinylimine

Abstract

Radical reaction of N-aziridinylimines generated 5- and 6-membered ring radicals from acyclic radical precursors. Based on this finding, consecutive carbon-carbon bond formation could be achieved and this approach turned out to be very effective to form quarternary carbon centers in a single synthetic operation. This consecutive carbon-carbon bond formation approach was applied to synthesize naturally occurring sesquiterpenes such as modhephene, cedranoids, and quadrone. Racemic modhephene having [3.3.3.0] propellane skeleton was synthesized from readily available $\alpha$,$\alpha$-disubstituted cyclopentanone aziridinylimine using the tandem radical cyclization of N-aziridinylimine, demonstrating the efficiency and usefulness of consecutive carbon-carbon bond formation approach. Furthermore, the cyclization proceeded in a stereoselective manner. The present approach could be successfully applied to construct [5.3.1.$0^1.5$] and [6.2.1.$0^1.5$] skeletons,which consisted of naturally occurring cedranoids and prelacinan-7-ol, respectively. Similarly, cedranoids such as cedrene, cedrone, and cedrol could be efficiently synthesized via tandem radical cyclization of N-aziridinylimines. The present synthesis was much simpler and more efficient than previously reported synthetic methods. Synthetic studies of silphinene and quadrone were investigated. The key intermediates were prepared in high yields. However, radical cyclizations did not give the desired products and the reasons for the failure are unclear at the present.