title: A Pd(0)-mediated indole (macro)cyclization reaction.
abstract: Herein we report a systematic study of the Larock indole annulation designed to explore the scope and define the generality of its use in macrocyclization reactions, its use in directly accessing the chloropeptin I versus II DEF ring system as well as key unnatural isomers, its utility for both peptide-derived and more conventional carbon-chain based macrocycles, and its extension to intramolecular cyclizations with formation of common ring sizes. The studies define a powerful method complementary to the Stille or Suzuki cross-coupling reactions for the synthesis of cyclic or macrocyclic ring systems containing an embedded indole, tolerating numerous functional groups and incorporating various (up to 28-membered) ring sizes. As a result of the efforts to expand the usefulness and scope of the reaction, we also disclose a catalytic variant of the reaction, along with a powerful Pd(2)(dba)(3)-derived catalyst system, and an examination of the factors impacting reactivity and catalysis.
authors.affiliation: Department of Chemistry and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: Steven P
authors.initials: SP
authors.lastname: Breazzano
authors.forename: Yam B
authors.initials: YB
authors.lastname: Poudel
authors.forename: Dale L
authors.initials: DL
authors.lastname: Boger
mesh_terms: D003500:Cyclization; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry; D047028:Macrocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry*; D010165:Palladium / Q000737:chemistry*
chemical_list: D007211:Indoles; D047028:Macrocyclic Compounds; D009942:Organometallic Compounds; D010165:Palladium