Ambruticins: tetrahydropyran ring formation and total synthesis

James I Bowen1, Luoyi Wang2, Matthew P Crump1

  • 1School of Chemistry, University of Bristol, Bristol, BS8 1TS, UK. chris.willis@bristol.ac.uk.

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The Hofmann and Curtius rearrangement reactions can be applied to synthesize primary amines from carboxylic acid derivatives such as amides and acyl azides. In the Hofmann rearrangement, a primary amide undergoes deprotonation in the presence of a base, followed by halogenation to generate an N-haloamide. A second proton abstraction produces a stabilized anionic species, which rearranges to an isocyanate intermediate via an alkyl group migration from the carbonyl carbon to the neighboring...
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