Copper-Catalyzed Azide-Ynamide Cyclization for Generation of α-Imino Copper Carbenes: Divergent and Enantioselective Access to Polycyclic N-Heterocycles
Abstract: Here an efficient copper‐catalyzed cascade cyclization of azide‐ynamides via α‐imino copper carbene intermediates is reported, which represents the first generation of α‐imino copper carbenes from alkynes. This protocol enables the practical and divergent synthesis of an array of polycyclic N‐heterocycles in generally good to excellent yields with broad substrate scope and excellent diastereoselectivities. Moreover, such an asymmetric azide‐ynamide cyclization has been achieved with high enantioselectivities (up to 98:2 e.r.) by employing BOX‐Cu complexes as chiral catalysts. Thus, this protocol constitutes the first example of asymmetric azide‐alkyne cyclization. The proposed mechanistic rationale for this cascade cyclization is further supported by theoretical calculations.