Asymmetric oxidative cation/olefin cyclization of polyenes: evidence for reversible cascade cyclization.

The biosynthesis of cyclic terpenes from polyene precursors by cyclase enzymes is one of nature’s most elegant chemical transformations.[1] The ease with which nature creates complex molecular architectures from achiral precursors has motivated efforts to develop similarly powerful synthetic methodologies.[2] Alimited number of asymmetric methods have been developed,[3] including the notable Brønsted/Lewis acid (BLA) cascade reactions developed by Yamamoto and co-workers,[4] and the recent halocyclization of polyprenoids reported by Ishihara and co-workers.[5] We recently reported a regioand diastereoselective oxidative polycyclization of diand trienols catalyzed by achiral [(dppe)Pt] dications, wherein turnover was achieved by the trityl cation abstracting a hydride from a putative [(dppe)Pt-H]+ intermediate (Scheme 1).[6,7] Since there are so few asymmetric methods for such cascade cyclizations,[8] we initiated efforts to render this initial discovery into an oxidative method that was regio-,[9] stereo-, and enantioselective.[10,11] In the course of discovering and then subsequently mechanistically examining such an enantioselective variant, we have also made the surprising observation that the initial cascade cyclization is not necessarily the stereochemistry-determining step.