Collective Synthesis of Diverse Onoceroids via Chelation-Assisted Radical Cross-Coupling

Onoceroids are complex triterpenoids that arise through bidirectional cyclizations of squalene or its diepoxide derivative, followed by oxidative tailorings. By virtue of this biosynthetic sequence, many onoceroids possess unsymmetrical pseudodimeric structures, which present an unusual synthetic challenge. In this study, we describe a family-level solution to the synthesis of all known subtypes of onoceroid skeleton. A key feature in this study is the discovery of an important chelation effect that facilitates high cross-selectivity in radical C(sp 3)-C(sp 3) cross-coupling between two highly similar but distinct fragments. Combining this process with other modern radical reactions enables rapid access to more than 20 naturally occurring onoceroids. This study provides a blueprint for constructing sp 3-rich polycyclic architectures through the combination of modern synthetic paradigms.