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

The diversified synthesis of chiral fluorinated cyclobutane derivatives has remained a difficult task in synthetic chemistry. Herein, we present an approach for asymmetric hydroboration and formal hydrodefluorination of gem‐difluorinated cyclobutenes through rhodium catalysis, providing chiral gem‐difluorinated α‐boryl cyclobutanes and monofluorinated cyclobutenes with excellent regio‐ and enantioselectivity, respectively. 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 in some cases, 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 that provide a platform for the synthesis of enantioenriched fluorinated cyclobutane derivatives to a great diversity. The first asymmetric hydroboration of cyclobutenes using Rh catalysis is reported, providing gem‐difluorinated α‐boryl cyclobutanes in excellent regio‐ and enantioselectivity. Upon in situ B,F‐elimination (Pd is required for R=aryl), monofluorinated cyclobutenes are obtained through formal hydrodefluorination. Versatile downstream transformations make this method a platform for the diversified synthesis of chiral fluorinated cyclobutanes.