Convergence of products from Povarov and von Miller reactions: approaches to helquinoline

Paul J. Stevenson*, Peizhao He, Brian Daly

*Corresponding author for this work

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Yttrium triflate or triflic acid catalysed Povarov reaction of methyl anthranilate with ethyl vinyl ether, both as aldehyde surrogate and as alkene, gave the desired 2-methyl-4-ethoxytetrahydroquinoline diastereoisomers as the major products along with four component coupling von Miller adducts. A proton NMR-study, using yttrium triflate as catalyst, revealed that the cis-diastereoisomers were the initial major products in both the Povarov and von Miller reactions but that these isomerised to the trans-diastereoisomers under the reaction conditions. Two distinct pathways for forming von Miller adducts were uncovered with the initial Povarov products being converted to von Miller adducts under the reaction conditions. Replacement of the 4-ethoxy with a 4-methoxy group under acidic conditions gave predominantly the trans-diastereoisomer, which was subsequently converted to a cis/trans mixture of the tetrahydroquinoline antibiotic helquinoline. It was also possible to convert the von Miller products to Povarov products under acidic conditions

Original languageEnglish
Pages (from-to)7350-7357
Number of pages8
JournalTetrahedron
Volume70
Issue number40
Early online date26 Jun 2014
DOIs
Publication statusPublished - 07 Oct 2014

Keywords

  • Povarov reaction
  • Von Miller reaction
  • Lewis acid catalysis
  • Helquinoline
  • Multi-component coupling
  • Alkaloid
  • DIELS-ALDER REACTIONS
  • ENANTIOSELECTIVE SYNTHESIS
  • MARTINELLIC ACID
  • ALKALOIDS MARTINELLINE
  • COOPERATIVE CATALYSIS
  • QUINOLINE SYNTHESIS
  • COUPLING REACTIONS
  • HETEROCYCLIC CORE
  • TRIFLIC ACID
  • LEWIS-ACID

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