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

Abstract

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.