Pd-Catalyzed Borylation in Water and Its Application to the Synthesis of Active Pharmaceutical Ingredient (API) Intermediates

J Org Chem. 2024 Sep 6;89(17):12452-12461. doi: 10.1021/acs.joc.4c01389. Epub 2024 Aug 19.

Abstract

An efficient catalytic borylation reaction of aryl bromides in water based on Pd catalysis under micellar conditions is presented. The peculiar combination of the proper Pd precursor with a Sphos ligand and a hindered lipophilic base ensures good yields in the synthesis of a wide range of boronic esters, even for heteroaryl derivatives with a good purity profile. The method is specifically developed for the in situ preparation of boronic esters that are directly converted into examples of relevant active pharmaceutical ingredient intermediates through cross-coupling reactions or via oxidation to phenols.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Boronic Acids / chemistry
  • Catalysis
  • Esters / chemistry
  • Molecular Structure
  • Palladium* / chemistry
  • Pharmaceutical Preparations / chemical synthesis
  • Pharmaceutical Preparations / chemistry
  • Water* / chemistry

Substances

  • Palladium
  • Water
  • Pharmaceutical Preparations
  • Esters
  • Boronic Acids