DFT Calculation-Assisted Design of Precursors for Nucleophilic 2-Amino Allyl Cations and Their Application in [3 + 2] Cycloaddition with Electron-Deficient Alkenes

In this work, we developed nucleophilic 2-aminoallyl cations guided by DFT calculations. Computational insights enabled a comprehensive analysis of factors governing N-nucleophilicity and an accurate prediction of cycloaddition reactivity with electron-deficient alkenes. Notably, this study represents the first asymmetric [3 + 2] cycloaddition of amino-allyl cations with exocyclic double bonds, enabling the efficient synthesis of spiro-pyrrolidines with excellent diastereoselectivities and enantioselectivities. Furthermore, the successful gram-scale preparation and derivatization of the products clearly demonstrate the synthetic utility of this methodology.