Effect of Conformation on the Reductive Cleavage of Methoxy-Substituted Aromatics under Electron Transfer Conditions

Much interest has been devoted in the past years to the study of the relationships between conformation of methoxy-substituted aromatics and their biological activity (1) Similar relationships seem to hold also for the regioselectivity of reductive cleavage of alkoxyaromatics under electron transfer conditions. As an example, it was recently suggested, based on the persistency of ESR spectra of radical anions of aryl methyl ethers and INDO calculation (2), that a conformation of the methoxy group coplanar to the aromatic ring should favor O-Me cleavage (demethylation). As an extention of our research on the reductive demethoxylation of aromatic substrates by alkali metals (3) we have studied the reactivity of substrates in which the methoxy (or alkoxy) group is forced either in an orthogonal conformation ( like 1 and 2), or in a almost planar conformation (like 3). Under our reaction conditions (Na or K metal, isooctane or THF) 1 and 3 underwent prevalent demethoxylation, whereas 2 underwent exclusive dealkylation. This indicates that the competition between dealkoxylation and dealkylation is influenced, inter alia, not only by conformation effect but also, perhaps more significantly, by substituents effects.