Thermally Activated Geometrical Regioselective E→Z Isomerization‐Enabled Cascade Sequences of Conjugated Dienals: Experimental and DFT Studies

Abstract

The geometrical regioselective E → Z isomerization of a conjugated alkene under thermal activation poses a challenge due to microscopic reversibility. Herein we report that such reversibility issues can be circumvented by integrating E → Z isomerization with subsequent cyclization cascade. Thus, linearly conjugated dienals in a mixture of toluene‒alcohol (2:1) solvents or only with alcohol at 60‐70 °C can be converted to γ‐alkoxybutenolides in moderate to good yields. The intermediary 2Z,4E‒isomer can be isolated, which includes the first example of isolating the regioselective isomerization product under thermal conditions. Density functional theory (DFT) studies have been employed to shed light on the feasibility of geometrical alkene isomerization and ensuing cascade sequences. It has been observed that the regioselective 2E,4E → 2Z,4E isomerization of dienal is a thermodynamically facile (ΔG < 0) process. The thermodynamic plausibility of the subsequent cascade reaction from the Z‐isomer to the anticipated product in the presence of a polar protic solvent (here MeOH) is also explicated. Out of the two probable pathways, the "hemiacetal pathway" involving a relay proton transfer is kinetically more feasible due to the diminished activation barrier than the conjugate addition pathway.