Stereodivergent Synthesis of Perhydrobenz[e]indene Terpenoids

Abstract

The development of stereodivergent synthetic methods has enormous potential in total synthesis owing to their ability to unify and streamline strategies toward a large collection of natural products. In this article, we describe a stereodivergent Rautenstrauch rearrangement in which a choice of Au- or Pd-based catalyst provided a uniform entry toward all four possible stereoisomers of the 6/6/5 tricyclic core of perhydrobenz[e]indene terpenoids. Alongside the development of a general strategy to access the core scaffolds of these unique families of metabolites, computational studies rationalized the observed diastereoselectivity during key cyclizations. Ultimately, these studies led to the total syntheses of several distinctive perhydrobenz[e]indene natural products, including N-acetyl-polyveoline, dasyscyphin B, and rhabdastin B.