The primary objective of this research is to continue to develop at an advanced level the utility of [3,3] sigmatropy for the construction of complex terpenes of widely varied structural type. This methodology gives every indication of being a very important advance in our ability to access diverse classes of important natural products in a concise and stereocontrolled manner. These new strategies are based on the further exploitation of the anionic oxy-Cope and Claisen rearrangements for con- struction of unusual medium-sized ring systems consisting of 7-10 constituent atoms. The latent applicability of many of the selected targets to various therapeutic areas make this phase of the program particularly timely and constitutes important added justification. An exceptionally short synthesis of cyathin B3 which exploits tandem kinetic resolution and oxy-Cope chemistry to construct the central seven-membered ring in stereocontrolled fashion with proper absolute configuration will be examined. In like fashion, an exceptionally short synthesis of crispolide that features rapid construction of bridgehead olefinic allylic hydroperoxides is planned. High levels of convergency characterize the planned elaboration of albolic acid and vinigrol. This aspect of the overall anionic oxy-Cope process has been seriously neglected in past studies and warrants considerable exploitation. The rapidity with which complex molecules can be elaborated by this technique is probably unrivaled. This tactic will also see service in our planned approach to verecynarmin A. In this instance, one of the two necessary building blocks is the naturally occurring furanoterpene evodone. In all of the above thrusts, analogues may be prepared in order o provide added insight into the flexibility of the respective protocols. Ring-expanding Claisen rearrangements are expected to facilitate the rapid contruction of several laurencin metabolites such as laurenyne and isolaureatin, as well as oxabicyclic diterpenoids of the eunicellane type. A process involving a novel two-fold Tebbe-Claisen sequence is to be developed and extended to a synthesis of ceroplastol I. Finally, two-fold adoption of the alicyclic Claisen rearrangement is to serve as the key stereochemical determinant in a projected route to cleomdolide.
