Silver-promoted Friedel–Crafts reaction: concise total synthesis of (−)-ardeemin, (−)-acetylardeemin and (−)-formylardeemin

Abstract

Total syntheses of multidrug resistant inhibitors (-)-acetylardeemin 2a, (-)-ardeemin 2b, and (-)-formylardeemin 3 have been achieved within 10 steps starting from bromopyrroloinoline 13. The key step involves direct alkylation of 13 with prenyl tributylstannane 11 to yield 12 via a silver-promoted asymmetric Friedel-Crafts reaction. Highly efficient installation of the isoprenyl group allowed excellent overall yield. Moreover, the substrate scope of the asymmetric Friedel-Crafts reaction of 13 was expanded to include a variety of arenes 14 to afford natural product-like library analogues 15.