Total Synthesis of Macrocarpines D and E via an Enolate-Driven Copper-Mediated Cross-Coupling Process: Replacement of Catalytic Palladium with Copper Iodide

Org Lett. 2016 Sep 2;18(17):4174-7. doi: 10.1021/acs.orglett.6b01526. Epub 2016 Aug 16.

Abstract

An enolate driven copper-mediated cross-coupling process enabled cheaper and greener access to the key pentacyclic intermediates required for the enantiospecific total synthesis of a number of C-19 methyl substituted sarpagine/macroline indole alkaloids. Replacement of palladium (60-68%) with copper iodide (82-89%) resulted in much higher yields. The formation of an unusual 7-membered cross-coupling product was completely inhibited by using TEMPO as a radical scavenger. Further functionalization led to the first enantiospecific total synthesis of macrocarpines D and E.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Catalysis
  • Copper / chemistry*
  • Iodides / chemistry*
  • Molecular Conformation
  • Palladium / chemistry*
  • Phloroglucinol / analogs & derivatives
  • Phloroglucinol / chemical synthesis*
  • Phloroglucinol / chemistry
  • Stereoisomerism

Substances

  • Iodides
  • Palladium
  • Copper
  • cuprous iodide
  • Phloroglucinol