Convenient Access to Chiral Cyclobutanes with Three Contiguous Stereocenters from Verbenone by Directed C(sp3)−H arylation.

This work demonstrates how a series of complex, chiral cyclobutane derivatives can be accessed in four steps from the terpene verbenone through the application of a directed C−H functionalization approach. The developed synthetic route involved an 8‐aminoquinoline‐directed C(sp3)−H arylation as the key step, and this reaction could be carried out with a wide range of aryl and heteroaryl iodides to furnish a variety of cyclobutane products with three contiguous stereocenters. Moreover, it was shown that the 8‐aminoquinoline auxiliary could be effectively removed from the cyclobutane derivatives using an ozonolysis‐based cleavage method. Three in a row: A short synthetic route to chiral and structurally elaborate cyclobutanes with three contiguous stereocenters from the terpene verbenone is presented. In the key step, a highly efficient directing‐group‐assisted C(sp3)−H arylation was used to install a wide range of aryl and heteroaryl substituents with excellent stereocontrol. Removal of the 8‐aminoquinoline directing group from these compounds was demonstrated using an ozonolysis‐based cleavage method. [ABSTRACT FROM AUTHOR]