Diversified Synthesis of Chiral Fluorinated Cyclobutane Derivatives Enabled by Regio‐ and Enantioselective Hydroboration

The diversified synthesis of chiral fluorinated cyclobutane derivatives has remained a tough task in synthetic chemistry. Herein, we present a switchable paradigm for asymmetric hydroboration and formal hydrodefluorination of gem-difluorinated cyclobutenes via rhodium catalysis, providing chiral gem-difluorinated α-boryl cyclobutanes and monofluorinated cyclobutenes with excellent regio- and enantioselectivity, respevtively. The key to the success of the two transformations relies on an efficient, mild and highly selective rhodium-catalyzed asymmetric hydroboration with HBPin (pinacolborane), in which the subsequent addition of a base, and a catalytic amount of palladium if necessary, results in the formation of formal hydrodefluorination products with the four-membered ring retained. The obtained chiral gem-difluorinated α-boryl cyclobutanes are versatile building blocks, which provides a platform for the synthesis of enantioenriched fluorinated cyclobutane derivatives to a great diversity.