A Novel, Short and Repeatable Two-Carbon Ring Expansion Reaction by Thermo-Isomerization: Easy Synthesis of Macrocyclic Ketones

Abstract

A novel two-carbon ring enlargement procedure, in which medium- and large-ring 1-vinylcycloalkanols are thermoisomerized in a flow reactor system at temperatures of 600 °C to about 650 °C, produces the isomeric ring-expanded cycloalkanones directly and efficiently. This two-step ring expansion protocol can easily be applied several times successively. For e.g., the musk odorant cyclopentadecanone (Exaltone ® ) is prepared from cycloundecanone in two repetitive cycles. Thermo-isomerization of the corresponding ethynylic cycloalkanols gives in moderate yields the bishomologous α,β-unsaturated macrocyclic (E)-2-cycloalkenones. A reaction mechanism via alkyl hydroxyallyl biradical intermediates is proposed.