Palladium-Catalyzed Reductive and Redox-Neutral Cyclization Approach to the Southern Core of Avermectins

The avermectins make up a biologically relevant class of complex natural products that continue to inspire the development of new strategies in chemical synthesis. Herein, we disclose a concise synthesis of the southern core of avermectin aglycon. The key hydrobenzofuran was forged by either reductive cyclization or cycloisomerization, both using a cationic palladium precatalyst. This hydropalladation strategy generated the hydrofuran ring under mild conditions, enabling the rapid construction of the tetra-substituted carbon stereocenter.