Controlled Generation of Unstabilized N -Alkyl Nitrile Imines Enables Regioselective (3 + 2) Cycloadditions with Diverse Dipolarophiles

Abstract N-Alkyl nitrile imines remain underdeveloped as intermediates for intermolecular cycloadditions. Here, we report their in situ generation and regioselective (3 + 2) cycloaddition with activated and unactivated alkenes and alkynes, affording N-alkyl pyrazolines and pyrazoles in good to excellent yields. The method accommodates broad variation in both reaction partners and enables gram-scale preparation of a key pyrazole fragment used in the synthesis of lenacapavir in a 79% yield over two steps.