The Grob/Eschenmoser fragmentation of cycloalkanones bearing beta-electron withdrawing groups: a general strategy to acyclic synthetic intermediates

Introduction of a beta-electron withdrawing group to cycloalkanones allows facile C-C bond fragmentation. The reaction has been demonstrated with a large range of ring sizes, bearing various leaving and electron withdrawing groups, and using a variety of nitrogen and oxygen containing nucleophiles (>30 examples). The application of fragmentation products to the preparation of substituted gamma-lactones has been demonstrated. Mechanistic studies are reported which are suggestive of a Grob/Eschenmoser type reaction.