Bradsher cycloaddition of 4-alkoxyisoquinolinium salts as a route to a fully functionalized B ring of the angucycline antibiotics

Article abstract of DOI:10.1021/jo00126a048

The title cycloaddition leads to a more complicated reaction manifold when there is an alkoxy group at C-4 of the isoquinoline salt. Whereas the earlier unsubstituted isoquinoline salts afforded materials from 1,4 cycloaddition, in the present examples, 1,4 and 1,3 cycloadducts are observed. Both simple and alkoxylated substrates yielded one-bond noncycloadduct materials. Careful product analysis suggests that the general mechanistic principles of the Bradsher reaction can account for all the observations in the alkoxyisoquinoline reactions. Cycloadduct 22 was carried through a short sequence to acetal 44, the first synthetic model for the 1-acyl-cis-1,2-dialkoxy-1,2-dihydronaphthalene framework of the sakyomicin class of the angucycline antibiotics.