Total synthesis of linoxepin facilitated by a Ni-catalyzed tandem reductive cyclization

A nickel-catalyzed reductive cyclization was developed to construct the tricyclic core embedded in linoxepin, a cyclolignan with a unique benzoxepin ring. The generated diastereodivergent acetals could be converted to the common unsaturated lactone, thus allowing a racemic synthesis of this molecule after incorporation of the remaining aromatic ring. This strategy with a late-stage installation of the D-ring led to the facile production of several linoxepin analogs as well.

Automated summary

A nickel-catalyzed reductive cyclization was developed to construct the tricyclic core of linoxepin. The generated diastereodivergent acetals can be converted to linoxepin analogs. This strategy facilitates the facile production of several linoxepin analogs.