Synthesis of the Taxol Core via Catalytic Asymmetric 1,4-Addition of an Alkylzirconium Nucleophile

Org Lett. 2020 Jun 5;22(11):4103-4106. doi: 10.1021/acs.orglett.0c01165. Epub 2020 May 12.

Abstract

The Taxol core was prepared in five steps via a key copper-catalyzed asymmetric conjugate addition trapping sequence. The use of a bromodiene-derived alkylzirconium nucleophile followed by trapping with POCl3/DMF gave a highly functionalized intermediate featuring a quaternary center in 69% yield with 92% ee. After 1,2-addition, Suzuki-Miyaura cross-coupling, allylic oxidation, and a type II intramolecular Diels-Alder reaction, the taxol core was obtained in 11% overall yield with 92% ee.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Catalysis
  • Copper / chemistry*
  • Cycloaddition Reaction
  • Molecular Structure
  • Organometallic Compounds / chemistry*
  • Paclitaxel / chemical synthesis*
  • Paclitaxel / chemistry
  • Zirconium / chemistry*

Substances

  • Organometallic Compounds
  • Copper
  • Zirconium
  • Paclitaxel