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Skeletal Editing Approach to Bridge-Functionalized Bicyclo[1.1.1]pentanes from Azabicyclo[2.1.1]hexanes.

Brandon A WrightAnastassia MatviitsukMichael J BlackPablo García-ReynagaLuke E HannaAaron T HerrmannMichael K AmeriksRichmond SarpongTerry P Lebold
Published in: Journal of the American Chemical Society (2023)
Azabicyclo[2.1.1]hexanes (aza-BCHs) and bicyclo[1.1.1]pentanes (BCPs) have emerged as attractive classes of sp 3 -rich cores for replacing flat, aromatic groups with metabolically resistant, three-dimensional frameworks in drug scaffolds. Strategies to directly convert, or "scaffold hop", between these bioisosteric subclasses through single-atom skeletal editing would enable efficient interpolation within this valuable chemical space. Herein, we describe a strategy to "scaffold hop" between aza-BCH and BCP cores through a nitrogen-deleting skeletal edit. Photochemical [2+2] cycloadditions, used to prepare multifunctionalized aza-BCH frameworks, are coupled with a subsequent deamination step to afford bridge-functionalized BCPs, for which few synthetic solutions currently exist. The modular sequence provides access to various privileged bridged bicycles of pharmaceutical relevance.
Keyphrases
  • crispr cas
  • tissue engineering
  • quantum dots
  • molecularly imprinted
  • amino acid
  • molecular dynamics
  • adverse drug
  • mass spectrometry
  • drug induced
  • liquid chromatography
  • simultaneous determination