Regio- and Stereoselective Rhodium(II)-Catalyzed C-H Functionalization of Cyclobutanes

Recent developments in controlled C-H functionalization transformations continue to inspire new retrosynthetic disconnections. One tactic in C-H functionalization is the intermolecular C-H insertion reaction of rhodium-bound carbenes. These intermediates can undergo highly selective transformations through the modulation of the ligand framework of the rhodium catalyst. This work describes our continued efforts toward differentiating C-H bonds in the same molecule by judicious catalyst choice. Substituted cyclobutanes that exist as a mixture of interconverting conformers and possess neighboring C-H bonds within a highly strained framework are the targets herein for challenging the current suite of catalysts. Although most C-H functionalization tactics focus on generating 1,2-disubstituted cyclobutanes via substrate-controlled directing-group methods, the regiodivergent methods discussed in this paper provide access to chiral 1,1-disubstituted and cis-1,3-disubstituted cyclobutanes simply by changing the catalyst identity, thus permitting entry to novel chemical space.