Tf2O‑Mediated Cyclization of 7‑Enamides: Bioinspired Construction of Fused Eight-Membered Carbocyclic Enimines and Enones

• Published in: Journal of organic chemistry 2021-12, Vol.86 (23), p.16926-16939
• Main Authors: Yu, Si-Jia, Ye, Jian-Liang, Hong, Ya-Cheng, Huang, Pei-Qiang
• Format: Article
• Language: English
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/acs.joc.1c02098

In this paper, we document the construction of functionalized and fused eight-membered carbocycles by the triflic anhydride-mediated cyclization of 7-enamides. Taking advantage of the high electrophilicity of the nitrilium ion intermediates, generated in situ from secondary N-(2,6-dimethyl)­anilides, the nonactivated, trisubstituted alkene–nitrilium cyclization reactions proceeded smoothly to afford nonconjugated β,γ-enimines (for fused 6/6/8 ring systems), conjugated α,β-enimines (for 6/5/8), or fused 5/8 ring systems in good yields. When the cyclization reactions were followed by one-pot acidic hydrolysis, the reaction led directly to the corresponding α,β-enones. For some substrates, the reaction afford an efficient access to pendent cyclic β,γ-enimines/enones.