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-exo-dig cyclizations. Two sets of substrates, one containing disubstituted alkyne functional groups and the other featuring terminal alkynes, were synthesized by using O-propargylation, Sonogashira cross-coupling, and condensation reactions between aldehydes and o-diaminobenzene. While the disubstituted substrates yielded exocyclic E/Z 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-exo-dig 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 O-to-N-propargyl transfer reactions, followed by 7-exo-dig 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.

Journal

JOURNAL OF ORGANIC CHEMISTRY

Year

2025

Volume

90

Issue

13

Pages

4675-4689

ISSN

0022-3263

eISSN

1520-6904

DOI

10.1021/acs.joc.5c00106

WoS UID

WOS:001455592400001

Open via DOI