Total Synthesis of (±)-Brazilin Using [4 + 1] Palladium-Catalyzed Carbenylative Annulation.

Palladium-catalyzed carbene insertion was utilized in a formal synthesis of (±)-picropodophyllone and a total synthesis of (±)-brazilin. All prior syntheses of brazilin have involved a Friedel-Crafts alkylation in the key carbon-carbon bond forming events. The palladium-catalyzed [4 + 1] reaction generates a 1-arylindane with all of the functionalities needed for formation of the indano[2,1-]chroman ring system of brazilin. The synthesis of (±)-brazilin was achieved in 11 steps (longest linear sequence) with an overall 11% yield.