Palladium-Catalyzed Oxidative Direct C3- and C7-Alkenylations of Indazoles: Application to the Synthesis of Gamendazole

Org Lett. 2015 Sep 4;17(17):4320-3. doi: 10.1021/acs.orglett.5b02136. Epub 2015 Aug 26.

Abstract

The first palladium-catalyzed oxidative alkenylation of (1H)- and (2H)-indazole derivatives with various olefins is described. The use of Pd(OAc)2 as the catalyst and Ag2CO3 as the oxidant promoted the selective C3-monoalkenylation of (1H)-indazoles and (2H)-indazoles, affording the desired products in good yields. An original oxidative C7-alkenylation of 3-substituted (1H)-indazoles was also developed. The oxidative alkenylation of (1H)-indazole was successfully applied to the total synthesis of the drug candidate gamendazole in a step- and atom-economical fashion.

MeSH terms

  • Alkenes / chemistry
  • Catalysis
  • Indazoles / chemical synthesis*
  • Indazoles / chemistry
  • Molecular Structure
  • Oxidants / chemistry
  • Oxidation-Reduction
  • Palladium / chemistry*
  • Stereoisomerism

Substances

  • Alkenes
  • Indazoles
  • Oxidants
  • gamendazole
  • Palladium