A new strategy for the synthesis of cyclic terpenoids based on the radical opening of acyclic epoxypolyenes.

The cationic cyclization of polyenes has proved to be a useful tool in the synthesis of natural terpenic products.1 During recent years biomimetic approaches using radical chemistry have also been described.2,3 One of the most efficient is based on Mn(III) chemistry, which in the presence of Cu(II) resolves one of the main problems involved in radical reactions, the loss of funcionality.4,5 Another method is that of using Ti(III)6 complexes to promote the homolytic opening of epoxides and the addition of the resulting radical to an alkene, forming five-membered rings.7,8 In this case the reaction normally ends in the protonolysis of the organometallic intermediate, although the use of other electrophiles leads to more functionalized final products.7a Our recent research has been into the synthesis of terpenes with functionalized cyclohexane skeletons (Figure 1) via the electrophilic opening of acyclic epoxypolyenes.9 This approach leads to oxabicyclic compounds, which can be further elaborated (Scheme 1). Our intention in this note is to describe a more efficient approach to obtain this kind of terpene skeleton and if possible to generalize to other types of skeleton under mild reaction conditions, since direct policyclizations of epoxides of natural polyenes usually give complex mixtures of products and low yields (less than 10%) of polycyclic compunds.10 To this end we decided to apply a technique involving the homolytic opening of epoxides with Ti(III) complexes to acyclic epoxypolyenes under reaction conditions that give rise to an oxidative termination step.11