Base-Mediated Synthesis of Imidazole-Fused 1,4-Benzoxazepines via 7-<i>exo-dig</i> Cyclizations: Propargyl Group Transformation

Herein, we describe the synthesis of a series of imidazole-fused 1,4-benzoxazepines using 7-<i>exo-dig</i> cyclizations. Two sets of substrates, one containing disubstituted alkyne functional groups and the other featuring terminal alkynes, were synthesized by using <i>O</i>-propargylation, Sonogashira cross-coupling, and condensation reactions between aldehydes and <i>o</i>-diaminobenzene. While the disubstituted substrates yielded exocyclic <i>E</i>/<i>Z</i> configured cyclization products smoothly, the reactions involving terminal alkynes resulted in the formation of isomeric products with altered skeletal structures, in addition to the expected 7-<i>exo-dig</i> cyclization products. Density functional theory (DFT) calculations were used to clarify the mechanisms underlying the formation of these products. It is suggested that these unexpected products are formed through a series of intermolecular <i>O</i>-to-<i>N</i>-propargyl transfer reactions, followed by 7-<i>exo-dig</i> cyclization, in accordance with Baldwin's rules. Furthermore, this study extensively demonstrates the conversion of exocyclic products to endocyclic products through a base-mediated 1,3-H shift.