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 towards differentiating C-H bonds in the same molecule by judicious catalyst choice. Substituted cyclobutanes which 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. While most C-H functionalization tactics focus on generating 1,2-disubstituted cyclobutanes via substrate-controlled directing group methods, the regiodivergent methods 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.