A Torquoselective Thermal 6π‐Electrocyclization Approach to 1,4‐Cyclohexadienes via Solvent‐Aided Proton Transfer: Experimental and Theoretical Studies

Abstract

The thermal 6π‐electrocyclization of hexatriene typically delivers 1,3‐cyclohexadiene (1,3‐CHD). However, there is only limited success in directly synthesizing 1,4‐cyclohexadiene (1,4‐CHD) using such an approach, probably due to the difficulty in realizing thermally‐forbidden 1,3‐hydride shift after electrocyclic ring closure. The present study shows that by heating (2E,4E,6E)‐hexatrienes bearing ester or ketone substituents at the C1‐position in a mixture of toluene/MeOH or EtOH (2:1) solvents at 90‐100 °C, 1,4‐CHDs can be selectively synthesized. This is achieved through a torquoselective disrotatory 6π‐electrocyclic ring closure followed by a proton‐transfer process. The success of this method depends on the polar protic solvent‐assisted intramolecular proton transfer from 1,3‐CHD to 1,4‐CHD, which has been confirmed by deuterium‐labeling experiments. There are no reports to date for such a solvent‐assisted isomerization. Density functional theory (DFT) studies have suggested that forming 1,3‐CHD and subsequent isomerization is a thermodynamically feasible process, regardless of the functional groups involved. Two possible successive polar solvent‐assisted proton‐transfer pathways have been identified for isomerization.