[2+1+1] Assembly of spiro beta-lactams by Rh(ii)-catalyzed reaction of diazocarbonyl compounds with azirines/isoxazoles

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Abstract

A domino synthesis of dispiro-fused N-vinyl beta-lactams from diazo-Meldrum's acid and 2H-azirines or 5-alkoxyisoxazoles via the "2-azabuta-1,3-diene formation/Staudinger ketene-imine cycloaddition" sequence is described. The Rh-2(Piv)(4)-catalyzed formation of the 2-azabuta-1,3-diene intermediates in the first stage of the reaction sequence proceeds via addition of the rhodium carbenoid to the azirines/isoxazoles and provides the first example of the generation of iminium-type ylides from diazo-Meldrum's acid. This methodology was extended to monospiro-beta-lactams, which were synthesized in two steps using acyclic alpha-diazocarbonyl compounds in the stage of the formation of 2-azabuta-1,3-dienes. The method allows for the rapid assemblage of the carbon part of the azetidin-2-one system from diazo compounds only and affords spiro- and dispiro-beta-lactams in moderate yields. A bromine atom in the 2-bromoalkenyl moiety of the synthesized beta-lactams can be easily substituted by hydrogen under catalytic hydrogenation conditions or by 2-pyridyl-substituent via the Stille cross-coupling reaction.

Original languageEnglish
Pages (from-to)6821-6830
Number of pages10
JournalOrganic and Biomolecular Chemistry
Volume17
Issue number28
DOIs
StatePublished - 28 Jul 2019

Keywords

  • CARBENOID FUNCTIONALIZATION
  • RHODIUM CARBENOIDS
  • CYCLOADDITION REACTION
  • DIAZO-COMPOUNDS
  • KETENES
  • IMINES
  • ESTERS
  • DIAZOKETONES
  • INSERTION
  • COPPER

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