title: A Practical, Multi-gram Synthesis of (±)-Herbindole A, (±)-Herbindole B, and (±)-Herbindole C from a Common Intermediate via 6,7-Indole Aryne Cycloaddition and Pd(0)-Catalyzed Cross-Coupling Reactions.
abstract: A practical, multi-gram 10-step synthesis of racemic herbindole A, B, and C from a common intermediate is described. The key step features a remarkably regioselective C-7 metal-halogen exchange and elimination from a Bartoli-generatedN-t-butyldimethylsilyl-4,6,7-tribromo-5-methylindole scaffold to afford the 6,7-indole aryne. Cycloaddition with cyclopentadiene, oxidative cleavage, and Fujimoto reduction gave a common intermediate from which all three herbindoles were readily derived. A final Pd(0)-catalyzed Negishi and Stille cross-coupling reaction at the C-4 bromide afforded each of the herbindoles on a multigram scale.
authors.affiliation: Department of Chemistry, University of Missouri, 205 Kenneth A. Spencer Chemical Laboratories, 5100 Rockhill Road, Kansas City, MO 64110.
authors.forename: Nalin
authors.initials: N
authors.lastname: Chandrasoma
authors.affiliation: Center of Excellence in Chemical Methodologies and Library Development (KU-CMLD), University of Kansas, Delbert M. Shankel Structural Biology Center, 2034 Becker Drive, Lawrence, KS 66047.
authors.forename: Sivadarshini
authors.initials: S
authors.lastname: Pathmanathan
authors.affiliation: Department of Chemistry, University of Missouri, 205 Kenneth A. Spencer Chemical Laboratories, 5100 Rockhill Road, Kansas City, MO 64110 ; Center of Excellence in Chemical Methodologies and Library Development (KU-CMLD), University of Kansas, Delbert M. Shankel Structural Biology Center, 2034 Becker Drive, Lawrence, KS 66047.
authors.forename: Keith R
authors.initials: KR
authors.lastname: Buszek
keywords: Bartoli; Negishi; aryne; cross-coupling; cycloaddition; herbindole; hetaryne; indole; indolyne; trikentrin