Rapid construction of a diterpene-inspired tetracyclic skeleton bearing bicyclo[3.2.1]octane rings based on desymmetrization of 1,3-diketones

Abstract

A synthetic methodology for constructing ent-kaurane-like tetracyclic skeletons possessing a bicyclo[3.2.1]octane moiety has been developed by employing a desymmetrizing sequential cyclization strategy. Using a symmetric diketone as a key branching point, the sequence of desymmetric Friedel–Crafts cyclization and Pd-catalyzed intramolecular α-vinylation of ketone allowed us to construct the ent-kaurane-like tetracyclic skeleton from 1,3-cyclohexanedione in four steps. In contrast, reversing the order of the cyclization steps yielded a pseudo-symmetric tetracyclic skeleton, which is also reminiscent of the kaurane framework.