Cascade rearrangement of spiroepoxymethyl radicals into 2-oxocycloalkyl radicals: evaluation of a two-carbon cycloalkanone ring expansion

Series of 2-bromomethyl- and 2-hydroxymethyl-1-oxaspiro[2.n]alkanes were prepared from cycloalkanones by initial Wadsworth-Horner-Emmons methodology to afford ester-substituted methylenecycloalkanes. The latter were selectively reduced to hydroxymethylmethylenecycloalkanes which were epoxidised with peroxyacetic acid. Homolytic reactions were studied by EPR spectroscopy which enabled transient 3-oxoalk-1-enyl radicals, and their cyclisation products, 2-oxocycloalkyl and 2-oxocycloalkylmethyl radicals, to be characterised. This evidence, together with end product analyses of organotin hydride reductions of the 2-bromomethyl-1-oxaspiro[2.n]alkanes, established that the initial spiroepoxymethyl radicals rearranged by a three-stage cascade of two consecutive p-scissions followed by a cyclisation. Cyclisations of the 3-oxoalk-1-enyl radicals took place mainly in the endo-mode to afford 2-oxocycioalkyl radicals, except for the 5-oxohept-6-enyl radical for which exo-cyclisation to generate the 2-oxocyclohexylmethyl radical was preferred. Kinetic data for the exo- and endo-cyclisations of the 4-oxohex-5-enyl radical were obtained from tributyltin hydride mediated reactions of 2-bromomethyl-1-oxaspiro[2.3]hexane.