Proton Transfer Mechanism of Organocatalyzed Isomerization of Alkynoates into Allenoates: Enantioselectivity and Reversibility. A DFT Study

The mechanisms of organocatalyzed isomerization of alpha-unsubstituted (system I) and alpha-substituted (system II) alkynoates into allenoates mediated by benzothiadiazine catalyst were systematically investigated using the density functional theory (DFT) method. Four reaction paths in both systems were explored in detail, all involving two proton-transfer steps and some including a conformational change step in the intermediate. In all of these paths, the first proton transfer involves the proton (H7) of the substrate transferred to the amine nitrogen (N13) of the catalyst, giving the intermediate, and the other involves the same proton (H7) in the intermediate transferred back from the catalyst to the carbon atom (C6) of the substrate, forming the final product complex. The most favorable reaction path in system I, the anti-cis path, is very similar to the best path in system II, the anti-R path. The rate determining (first proton transfer) barrier height for the anti-cis path of system I is substantially smaller (by about 15 kJ/mol) than that for the anti-R path of system II, indicating that system I is more reactive than system II. The reverse barrier from the product complex back to the reactant complex in system I is only 20.4 kJ/mol higher than the forward barrier. On the other hand, the reverse barrier is 29.4 kJ/mol higher than the forward barrier in system II. Thus, making this isomerization in system I is more reversible at room temperature, while the isomerization in system II is irreversible. The origins of differences in reactivity, reversibility, and selectivity are revealed in terms of hydrogen-bond structures, charge distributions, and energy decomposition analysis of some key structures.