Toward a Predictive Understanding of Phosphine-Catalyzed [3+2] Annulation of Allenoates with Acrylate or Imine

Abstract

© 2018 American Chemical Society. Both theoretical and experimental studies were performed to explore the mechanism, regioselectivity, and enantioselectivity of phosphine-catalyzed [3 + 2] annulation between allenoates and acrylate or imine. Using density functional theory computations, we predicted that the enantioselective determining step is the nucleophilic addition of acrylate or imine to the catalyst-activated allenoate. In the key step, we proposed two hydrogen bonding interaction models (intermolecular H-bond model and intramolecular H-bond model). For acrylate substrates, the reaction proceeds via the intramolecular H-bond model and the strong noncovalent interactions between the 2-naphthyl ester moiety lead to the re-face attack pathway being more favorable. For imine substrates, the intermolecular H-bond model operates. In the annulation process, the bulky n-propyl oriented toward a crowded, sterically demanding environment plays a significant role in asymmetric induction. The theoretical calculation results agreed with experimental observations, and these results provide valuable insight into catalyst design and understanding of mechanisms of related reactions.