Multifaceted Substrate-Ligand Interactions Promote the Copper-Catalyzed Hydroboration of Benzylidenecyclobutanes and Related Compounds

A unified synthetic strategy to access tertiary four-membered carbo/heterocyclic boronic esters is reported. The use of a Cu(I) catalyst in combination with a modified 1,2-bis(diphenylphosphino)benzene (dppbz) ligand enables regioselective hydroboration of various trisubstituted benzylidenecyclobutanes and carbo/heterocyclic analogs. The reaction conditions are mild, and the method tolerates a wide range of medicinally relevant heteroarenes. The protocol can be conveniently conducted on a gram scale, and the tertiary boronic ester products undergo facile diversification into valuable targets. Reaction kinetics and computational studies indicate that the migratory insertion step is turnover-limiting and accelerated by electron-withdrawing groups on the dppbz ligand. Energy decomposition analysis calculations reveal that electron-deficient P-aryl groups on the dppbz ligand enhance the T-shaped pi/pi interactions with the substrate and stabilize the migratory insertion transition state.