An argument for abandoning the “allowed” and “forbidden” classification of electrocyclic reactions†

Abstract

The division of electrocyclic reactions into “allowed” and “forbidden” classes carries the implication that reactions of the latter class are so energetically penalised that they will occur only if their “allowed” alternatives are rendered effectively impossible. The present work tests that assumption, using NEVPT2 and DFT calculations on a variety of cyclobutene ring openings and (Z)-1,3,5-hexatriene ring closures, and their benzannelated congeners. The results show the assumption to be incorrect. The potential energy differences between “forbidden” and “allowed” transition states are found to cover a wide range of values, with the smallest being less than half the classical barrier to internal rotation of ethane. It follows that planning a total synthesis on the presumption that electrocyclic reactions will always follow the “allowed” stereochemical course is an unreliable strategy because other commonly occurring factors, such as routine steric and electronic substituent effects, can easily outweigh the electronic penalty for following the nominally forbidden mechansim. A particular case involving a proposed synthetic route to a class of anticancer compounds is highlighted as an example.