B(9)-OH- o -Carboranes: Synthesis, Mechanism, and Property Exploration.

Herein, we present a chemically robust and efficient synthesis route for B(9)-OH- o -carboranes by the oxidation of o -carboranes with commercially available 68% HNO 3 under the assistance of trifluoromethanesulfonic acid (HOTf) and hexafluoroisopropanol (HFIP). The reaction is highly efficient with a wide scope of carboranes, and the selectivity of B(9)/B(8) is up to 98:2. The success of this transformation relies on the strong electrophilicity and oxidizability of HNO 3 , promoted through hydrogen bonds of the Brønsted acid HOTf and the solvent HFIP. Mechanism studies reveal that the oxidation of o -carborane involves an initial electrophilic attack of HNO 3 to the hydrogen atom at the most electronegative B(9) of o -carborane. In this transformation, the hydrogen atom of the B-H bond is the nucleophilic site, which is different from the electrophilic substitution reaction, where the boron atom is the nucleophilic site. Therefore, this is an oxidation-reduction reaction of o -carborane under mild conditions in which N(V) → N(III) and H(-I) → H(I). The derivatization of 9-OH- o -carborane was further examined, and the carboranyl group was successfully introduced to an amino acid, polyethylene glycol, biotin, deoxyuridine, and saccharide. Undoubtedly, this approach provides a selective way for the rapid incorporation of carborane moieties into small molecules for application in boron neutron capture therapy, which requires the targeted delivery of boron-rich groups.