Synthesis of Macrocyclic Ketones by Repeatable Two-Carbon Ring Expansion Reactions


  • Matthias Nagel
  • Georg Fráter
  • Hans-Jürgen Hansen



Dynamic gas phase thermo-isomerization, Hydroxyallyl radicals, Macrocyclic ketones, Ring expansions


A novel and short method for the synthesis of macrocyclic alkanones has been developed: medium- and large-ring 1-vinylcycloalkanols can be transformed directly and efficiently into the isomeric, ring-expanded bishomologous macrocyclic ketones by a thermal 1,3-C shift rearrangement reaction in the gas phase, carried out under dynamic conditions in a flow reactor system at high temperatures. This two-carbon ring enlargement protocol involves only two steps and is easily repeatable, since the obtained cyclic ketones can directly be used as starting materials for the subsequent analogous two-carbon ring insertion reactions. Alkyl substituents at the vinylic side chain are transferred to the ring-expanded ketone as corresponding ?- and ?-substituents, respectively. Therefore, this thermo-isomerization process provides not only a short route to cycloalkanones but also to many alkyl-substituted macrocyclic ketones, such as, e.g. the musk odorant (±)-muscone. A reaction mechanism via alkyl hydroxyallyl biradical intermediates is proposed.




How to Cite

M. Nagel, G. Fráter, H.-J. Hansen, Chimia 2003, 57, 196, DOI: 10.2533/000942903777679398.