Total Synthesis of Boletopsin 11 Enabled by Directed ortho-C(sp2)-H Arylation

A nine-step synthesis of boletopsin 11 (1), a bioactive fungal natural product, is disclosed. Key features include a one-pot [O]-oxa-Michael cascade to establish the polyoxygenated dibenzofuran core followed by a Pd-catalyzed directed ortho-C(sp(2))-H arylation to complete the fully functionalized carbon skeleton. Exploration of the latter transformation led to the discovery of an unexpected tandem ortho-C(sp(2))-H arylation event, and the scope of the directed ortho-C(sp(2))-H reaction was further investigated with coupling partners varying in stereoelectronic properties.