Tandem Horner-Wadsworth-Emmons/Heck procedures for the preparation of 3-alkenyl-oxindoles: the synthesis of Semaxanib and GW441756

Jana Lubkoll, Alessia Millemaggi, Alexis Perry, Richard J. K. Taylor

Research output: Contribution to journalArticlepeer-review

Abstract

A tandem sequence involving Horner-Wadsworth-Emmons (HWE) olefination followed by a palladium-catalysed intramolecular Heck reaction has been developed to provide rapid access to 3-alkenyl-oxindoles from alpha-halo-anilides. This one-pot microwave accelerated process proceeds with catalytic palladium(II) acetate or tetrakis(triphenylphosphine)palladium, and has been used to prepare a range of adducts derived from aromatic, heteroaromatic and aliphatic aldehydes. The procedures can be used to prepare N-unprotected oxindoles directly and the applicability of the process has been established by carrying out one-pot syntheses of Semaxanib, an angiogenesis signalling inhibitor, and GW441756, an aza-oxindole Trk A inhibitor. (C) 2010 Elsevier Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)6606-6612
Number of pages7
JournalTetrahedron
Volume66
Issue number33
DOIs
Publication statusPublished - 14 Aug 2010

Keywords

  • Heck
  • Horner-Wadsworth-Emmons
  • Phosphonates
  • Palladium catalysis
  • Oxindoles
  • Tandem reactions
  • Semaxanib
  • GW441756
  • INTRAMOLECULAR HECK REACTION
  • PALLADIUM-CATALYZED CYCLIZATION
  • C-H FUNCTIONALIZATION
  • KINASE INHIBITORS
  • 3-SUBSTITUTED INDOLIN-2-ONES
  • OXINDOLES
  • DISCOVERY
  • CYCLOADDITION
  • DERIVATIVES
  • INDOLES

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