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 12via 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.