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

• Published in: Journal of the American Chemical Society 2023-04, Vol.145 (13), p.7331-7342
• Main Authors: Ma, Yan-Na, Ren, Huazhan, Wu, Yanxuan, Li, Na, Chen, Feijing, Chen, Xuenian
• Format: Article
• Language: English
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/jacs.2c13570

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% HNO3 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 HNO3, 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 HNO3 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.