Base-Free Catalytic Wittig-/Cross-Coupling Reaction Sequence as Short Synthetic Strategy for the Preparation of Highly Functionalized Arylbenzoxepinones

<jats:title>Abstract</jats:title><jats:p>The facile synthesis of highly functionalized building blocks with potential biological activity is of great interest to medicinal chemistry. The benzoxepinone core structures commonly exhibit biological activity. Thus, a short and efficient synthetic route towards benzoxepine containing scaffold, which enables late stage modification was developed. Namely, base-free catalytic Wittig reactions enabled the synthesis of bromobenzoxepinones from readily available starting materials. Subsequent, Suzuki–Miyaura and Stille reactions proved to be suitable methods to access a variety of benzoxepinone diaryl derivatives by late stage modification in only three steps. This three-step reaction sequence is suitable for high throughput applications and gives facile access to highly complex molecular structures, which are suitable for further functionalization. The antiproliferative properties of selected arylbenzoxepinones­ were tested in vitro on monolayer tumor cell line A549. Notably, in this initial screening, these compounds were found to be active in the micromolar range.</jats:p>