Aryloxymethyl radical cyclizations mimicking biological C–C bond formation to methoxy groups

Abstract

Attention is drawn to a small group of diverse natural products whose biosynthesis is unusual in involving formation of O-heterocyclic rings by C–C bond formation to aromatic methoxy groups, in net oxidative and non-oxidative processes. It is shown that aryloxymethyl radicals, generated by decarboxylation of thiohydroxamate esters of aryloxyacetic acids, undergo addition to both electron rich and electron poor double bonds, cyclizing in 5-exo, 6-endo and 6-exo fashions, and also substitute regioselectivity into pyridinium nuclei, thus mimicking the biochemical processes, as well as forming a useful new synthetic approach to O-heterocycles. Biosynthetic mechanisms are briefly discussed.