Achieving C(sp2)-C(sp3) Coupling with BCP-F2 Building Blocks via Barluenga Coupling: A Comparative Approach.

We report our efforts toward achieving C(sp2)-C(sp3) coupling reactions with 2,2-difluorobicyclo[1.1.1]pentane (BCP-F2) building blocks. By comparing the reactivities of matching pairs of bicyclo[1.1.1]pentane (BCP) and BCP-F2 analogues, we discovered that the Barluenga coupling reaction was the only cross-coupling protocol that translated well between the two structural motifs in contrast to other reported protocols. In this chemistry, a BCP-F2 bearing a tosylhydrazone functional group is cross-coupled with an arylboronic acid. These results further expanded the scope of BCP-F2 building blocks for potential applications in organic chemistry as well as medicinal chemistry.