Macrocyclisations using allylic radical intermediates. A new synthetic approach to natural 14-membered cembranoids

Abstract

A range of alternative radical macrocyclisation approaches to cembranoids have been evaluated. Radical macrocyclisations involving the allylic radicals 11 generated from the corresponding allylic iodides, 15b and 20b, in the presence of Bu₃SnH–AIBN, are shown to lead to 14-membered trienones, viz10, via selective 14-endo-trig processes. Both 10a and 10b can then be elaborated to the natural marine cembranoids 8(mukulol) and 9 respectively, by straightforward functional group interconversions.

Concise syntheses of the α,ω-dial 28, the terminal acetylenic aldehyde 27 and the allylic iodide enal 37 were developed, but neither was found to undergo radical mediated cyclisation to the corresponding 14-membered carbocycles 29, 30 and 38 respectively. Instead, only the products of reduction, e.g.39, or intermolecular pinacolisation, e.g.34 were produced.