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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.

SUBMITTER: Breazzano SP

PROVIDER: S-EPMC3560319 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

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A Pd(0)-mediated indole (macro)cyclization reaction.

Breazzano Steven P SP Poudel Yam B YB Boger Dale L DL

Journal of the American Chemical Society 20130117 4

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 complementa ...[more]

PMID: 23298368

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