Understanding the mechanisms, regioselectivies and enantioselectivities of the DMAP-catalyzed [2 + 4] cycloaddition of γ-methyl allenoate and phenyl(phenyldiazenyl)methanone

Abstract

The mechanisms, regioselectivities and enantioselectivities of the DMAP-catalyzed [2 + 4] cycloaddition reaction between γ-methyl allenoate R₁ and phenyl(phenyldiazenyl)methanone R₂ have been theoretically studied using density functional theory (DFT) calculations. Various possible reaction pathways are analyzed and discussed. The results of the DFT calculations show that the preferred mechanism (mechanism A) includes four steps: the nucleophilic addition of DMAP to R₁ to form the zwitterionic intermediate 1 (first step), the γ-addition of 1 to R₂ to generate intermediates γ-2(R&S) (second step), the intramolecular Michael addition to give the six-membered ring intermediates γ-3(RS&SR) (third step), and the catalyst DMAP liberation from γ-3(RS&SR) to generate the final product γ-P(R&S) (fourth step). The addition of DMAP to R₁ is calculated to be the rate-determining step. The reaction of 1 with R₂ is both the regioselective- and enantioselective-determining step. The calculated results are in good agreement with experimental findings. The present study may provide a useful guide not only for understanding other analogous reactions but also for designing new reactions in the future.