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(sp2)–H arylation to complete the fully functionalized carbon skeleton. Exploration of the latter transformation led to the discovery of an unexpected tandem ortho-C­(sp2)–H arylation event, and the scope of the directed ortho-C­(sp2)–H reaction was further investigated with coupling partners varying in stereoelectronic properties.