Solid-phase synthesis of 2,3,5-trisubstituted indoles

T Y Wu; S Ding; N S Gray; P G Schultz

doi:10.1021/ol016525t

Solid-phase synthesis of 2,3,5-trisubstituted indoles

Org Lett. 2001 Nov 29;3(24):3827-30. doi: 10.1021/ol016525t.

Authors

T Y Wu¹, S Ding, N S Gray, P G Schultz

Affiliation

¹ Department of Chemistry, Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.

PMID: 11720546
DOI: 10.1021/ol016525t

Abstract

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]