Base-Mediated Synthesis of Imidazole-Fused 1,4-Benzoxazepines via 7-<i>exo-dig</i> Cyclizations: Propargyl Group Transformation
Cokol, Nalan Korkmaz, Inyurt, Fevzi Can, Oktem, Ipek, Sahin, Ertan, Sari, Ozlem, Dengiz, Cagatay, Balci, Metin
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.
- Dergi
- JOURNAL OF ORGANIC CHEMISTRY
- Yıl
- 2025
- Cilt
- 90
- Sayı
- 13
- Sayfa
- 4675-4689
- ISSN
- 0022-3263
- eISSN
- 1520-6904
- DOI
- 10.1021/acs.joc.5c00106
- WoS UID
- WOS:001455592400001