Sequencing Groebke-Blackburn-Bienaymé and Aza-Michael Addition Reactions: A Modular Strategy for Accessing a Diverse Collection of Constrained Benzoxazepine and Imidazopyrazine Systems

We present a divergent strategy that permits access to diversely functionalized benzoxazepinium scaffolds fused to various heterocycles. The described strategy features a one-pot combination of the Groebke-Blackburn-Bienaymé reaction and an aza-Michael addition. Methyl (E)-4-(2-formylphenoxy)but-2-enoate and its derivatives are utilized as central elements in this cascade. These building blocks are reacted with a variety of functionalized amino-azines and tert -butyl isocyanide under ytterbium triflate [Yb(OTf) ₃] catalysis. The ensuing cascade represents a rapid, modular and atom-economic process that leads to the construction of a diverse collection of constrained benzoxazepinium systems from a wide substrate scope.