Ynamide Protonation-Initiated N-Heteropolyene Cyclization

<i>N</i>-containing polycyclic frameworks possessing consecutive chiral centers are widely found in a broad range of natural products and important bioactive molecules. Stereoselectively constructing their complex polycyclic frameworks represents a long-standing challenge. Herein, protonation of ynamide-initiated polyene cyclization was employed to construct such complex <i>N</i>-containing polycyclic skeletons, which are inaccessible or require tedious multiple-step strategies otherwise, with excellent stereoselectivity from a linear precursor. DFT calculations have been applied to understand the reaction mechanism, finding that a nonclassical carbocation intermediate with a cyclopropane ring is critical for controlling the diastereoselectivity of the present cyclization.