Organic Chemistry Portal >
Reactions > Organic Synthesis Search

Categories: Synthesis of O-Heterocycles > benzo-fused O-Heterocycles >

Synthesis of benzoxepines

Recent Literature

A base-promoted formal [4 + 3] annulation between 2-fluorophenylacetylenes and ketones provides a straightforward access to a wide range of functionalized benzoxepines in good yields. This transition-metal-free reaction proceeds through a tandem α-vinylation of the carbonyl compound followed by an intramolecular nucleophilic aromatic substitution (SNAr) reaction of the in situ generated β,γ-unsaturated ketone intermediates.
L. Ouyang, C. Qi, H. He, Y. Peng, W. Xiong, Y. Ren, H. Jiang, J. Org. Chem., 2016, 81, 912-919.

Readily available o-vinylphenols undergo a formal (5 + 2) cycloaddition to alkynes in the presence of catalytic amounts of [Cp*RhCl2]2 and Cu(OAc)2. The reaction generates highly valuable benzoxepine skeletons in a practical, versatile, and atom-economical manner. Using carbon monoxide instead of an alkyne as reaction partner leads to coumarin products of a formal (5 + 1) cycloaddition.
A. Seoane, N. Casanova, N. Quiñones, J. L. Mascareñas, M. Gulías, J. Am. Chem. Soc., 2014, 136, 650-652.

A simple and efficient base-mediated decarboxylative annulation of ynones with methyl 2-(2-bromophenyl)acetates provides a broad range of benzoxepines with high regioselectivity in good yields under transition-metal-free conditions. This method proceeds through a tandem [2 + 4] annulation, ring-opening decarboxylative reaction, and an intramolecular nucleophilic aromatic substitution reaction.
L.-L. Chen, F. Li, Q. Yang, Y.-F. Ye, W.-W. Yang, Y.-B. Wang, J. Org. Chem., 2023, 88, 3079-3088.

Various benzoxepines were constructed by a regioselective ring expansion concomitant with the introduction of an aryl group at position 5 via migratory insertion into a Pd carbene followed by C-C bond cleavage.
Y. Xie, P. Zhang, L. Zhou, J. Org. Chem., 2016, 81, 2128-2134.