Solid-phase synthesis of 2,3,5-trisubstituted indoles.
2,3,5-Trisubstituted indoles are synthesized in three steps starting from resin-bound aniline 2. R1 is introduced by a palladium-mediated coupling of the aryl iodide with terminal alkynes followed by intramolecular cyclization to form the indole core. Acylation at C-3 with an acid chloride in the presence of AlCl(3) catalyst introduces R2. The indole C-5 position is then diversified either by Sonagashira or Suzuki couplings with the aryl bromide. Finally, indole N-1 can be modified by post-cleavage methylation. [reaction: see text]
Wu
T Y
TY
Department of Chemistry, Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Ding
S
S
Gray
N S
NS
Schultz
P G
PG