1,2,4-Triazine vs. 1,3-and 1,4-Oxazinones in Normal- and Inverse-Electron-Demand Hetero-Diels-Alder Reactions: Establishing a Status Quo by Computational Analysis

We present an analysis of the well-known normal-and inverse-electron-demand hetero-Diels-Alder reaction involving 1,2,4-triazine, 1,3-oxazin-6-one, and 1,4-oxazin-2-one, with alkenes and alkynes, utilizing density functional theory (DFT) at the SCS-MP2/cc-pVDZ//B3LYP/6-31G(d) level to establish a theoretical status quo for synthetic practioners regarding the relative reactivities and stereochemical outcomes for these useful heterocycles. The results suggest that in the unsubstituted cases 1,2,4-triazine is less reactive in comparison to 1,3-oxazin-6-one and 1,4-oxazin-2-one for both reaction modes, whereas the cycloaddition regioselectivities depend largely on the diene. For example, 1,3-oxazin-6-one leads to kinetic meta isomers, in comparison to 1,2,4-triazine and 1,4-oxazin-2-one, which give rise to para isomers.