Group-Assisted Purification (GAP) Chemistry for the Synthesis of Velcade via Asymmetric Borylation of N-Phosphinylimines

Jian Bo Xie, Jian Luo, Timothy R. Winn, David B. Cordes, Guigen Li

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27 Scopus citations

Abstract

A new approach to the anticancer drug Velcade was developed by performing asymmetric borylation of an imine anchored with a chiral N-phosphinyl auxiliary. Throughout the 7-step synthesis, especially in the imine's synthesis and in the asymmetric borylation reactions, operations and work-up were conducted in simple and easy ways without any column chromatographic purification, which defines the GAP (group-assisted purification) chemistry concept. It was found that the optically pure isomer (dr > 99:1) can be readily obtained by washing the crude mixture of the asymmetric borylation reaction with hexane; the chiral N-phosphinyl auxiliary can be easily recovered after deprotection is finished. Several other N-phosphinylimines were also investigated for the asymmetric borylation reaction. The absolute configuration of the borylation product was confirmed by single crystal X-ray diffraction analysis.

Original languageEnglish
Pages (from-to)746-751
Number of pages6
JournalBeilstein Journal of Organic Chemistry
Volume10
DOIs
StatePublished - Mar 31 2014

Keywords

  • Asymmetric borylation
  • GAP chemistry
  • N-phosphinylimine
  • Organophosphorous
  • Velcade

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