Cobalt-Catalyzed Oxidase C-H/N-H Alkyne Annulation: Mechanistic Insights and Access to Anticancer Agents

Chemistry. 2016 May 10;22(20):6759-63. doi: 10.1002/chem.201601101. Epub 2016 Apr 8.

Abstract

Cp*-free cobalt-catalyzed alkyne annulations by C-H/N-H functionalizations were accomplished with molecular O2 as the sole oxidant. The user-friendly oxidase strategy proved viable with various internal and terminal alkynes through kinetically relevant C-H cobaltation, providing among others step-economical access to the anticancer topoisomerase-I inhibitor 21,22-dimethoxyrosettacin. DFT calculations suggest that electronic effects control the regioselectivity of the alkyne insertion step.

Keywords: C−H activation; annulation; cobalt; density functional calculations; isoquinolones; oxidase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkynes / chemistry*
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry*
  • Catalysis
  • Cobalt*
  • Coordination Complexes / chemistry
  • Heterocyclic Compounds, 4 or More Rings / chemical synthesis
  • Heterocyclic Compounds, 4 or More Rings / chemistry*
  • Isoquinolines / chemical synthesis
  • Isoquinolines / chemistry
  • Oxidoreductases / chemistry
  • Quantum Theory
  • Stereoisomerism
  • Thermodynamics
  • Topoisomerase I Inhibitors / chemical synthesis
  • Topoisomerase I Inhibitors / chemistry*

Substances

  • 21,22-dimethoxyrosettacin
  • Alkynes
  • Antineoplastic Agents
  • Coordination Complexes
  • Heterocyclic Compounds, 4 or More Rings
  • Isoquinolines
  • Topoisomerase I Inhibitors
  • Cobalt
  • Oxidoreductases