A Boron-Oxygen Transborylation Strategy for a Catalytic Midland Reduction

The enantioselective hydroboration of ketones is a textbook reaction requiring stoichiometric amounts of an enantioenriched borane, with the Midland reduction being a seminal example. Here, a turnover strategy for asymmetric catalysis, boron-oxygen transborylation, has been developed and used to transform the stoichiometric borane reagents of the Midland reduction into catalysts. This turnover strategy was demonstrated by the enantioselective reduction of ketones, including derivatives of biologically active molecules and those containing reducible groups. The enantioenriched borane catalyst was generated in situ from commercially available reagents, 9-borabicyclo[3.3.1]nonane (H-B-9-BBN) and beta-pinene, and B-O transborylation with pinacolborane (HBpin) was used for catalytic turnover. Mechanistic studies indicated that B-O transborylation proceeded by B-O/B-H boron exchange through a stereoretentive, concerted transition state, resembling sigma-bond metathesis.