DIPOLAR CYCLOADDITION ROUTE TO DIVERSE ANALOGS OF COCAINE - THE 6-SUBSTITUTED AND 7-SUBSTITUTED 3-PHENYLTROPANES

In our quest for an antagonist or partial agonist of cocaine, access t o certain 6- and 7-substituted 3-phenyltropanes of type I was required . Starting from 3-hydroxy-1-methyl-4-phenylpyridinium iodide, we discl ose a pyridinium betaine-based dipolar cycloaddition route to tropenon es of type II. In turn, we show how this intermediate can be transform ed to type I products either through the copper-catalyzed conjugate ad dition reaction of Grignard reagents to the enones 7-9 or by the coppe r(I)-catalyzed cross coupling reaction of the allylic acetates 15a and 16a with Grignard reagents.