Synthesis of flinderoles B and C by a gold-catalyzed allene hydroarylation

Abstract

The recent development of new gold(I) catalysis methodologies has opened the door to new disconnections for the total synthesis of bioactive complex molecules. Below is described the application of a gold(I)-catalyzed hydroarylation of an allene with indole toward the total synthesis of flinderoles B–C, members of a new class of antimalarial bisindole alkaloids isolated from plants of the Flindersia genus. The key gold(I) step establishes both the pyrrolidine and isobutenyl functionalities unique to these compounds. Other important steps of the synthesis include a convergent Horner–Wadsworth–Emmons olefination to construct the bridging alkene and a new strategy for α-indole enolate alkylations.