Synthesis of (Arylamido)pyrrolidinone Libraries through Ritter-Type Cascade Reactions of Dihydroxylactams

Peng Wu, Michael Åxman Petersen, Rico Petersen, Martin Ohsten Rasmussen, Karine Bonnet, Thomas Eiland Nielsen, Mads Hartvig Clausen

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

The Ritter-type reaction of arylnitriles and N-acyliminium ions generated in situ from dihydroxy-γ-lactams gave tetrahydropyrrolo[2,3-d]oxazol-5-ones in excellent yields. A subsequent acidic hydrolysis in EtOH/H2O/TFA (trifluoroacetic acid) yielded new (arylamido)pyrrolidinones with excellent cis diastereoselectivity. A combined one-step Ritter–hydrolysis procedure proved to be of equal efficiency. This versatile method, which was successfully used for the construction of a screening library containing 706 molecules within the European Lead Factory consortium, provides a simple way to access new compounds incorporating an arylamido and a pyrrolidinone moiety, both of which are widely found in marketed drugs and in biologically active molecules.
Original languageEnglish
JournalEuropean Journal of Organic Chemistry
Volume2015
Issue number25
Pages (from-to)5633-5639
Number of pages8
ISSN1434-193X
DOIs
Publication statusPublished - 2015

Keywords

  • Ritter reaction
  • Hydrolysis
  • Synthetic methods
  • Nitrogen heterocycles
  • Amides
  • Library synthesis

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