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

Abstract

Herein, we present a chemically robust and efficient synthesis route for B(9)-OH-o-carboranes by the oxidation of ocarboranes 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.

9,9′-Bis-o-carboranes: synthesis and exploration of properties

“…8 Palladium-catalyzed cross-coupling of B-halo-carboranes is also an efficient way to construct functional carboranes. 9 With HFIP as a solvent, our group achieved the selective B(9) electrophilic halogenation, 10 electrophilic amination, 11 and oxidation 12 of o -carboranes with >20 : 1 selectivity. With Pd(OAc) 2 as a catalyst, selective B(9) amination was also established, but with a relatively lower selectivity compared with electrophilic substitution reactions.…”

“…Based on our previous work, 10–13 a plausible reaction mechanism is proposed in Scheme 3. Firstly, the reaction of Pd(OAc) 2 and HOTf formed highly active electron-deficient Pd( ii ) species Pd(OTf) 2 .…”

Trifluoromethanesulfonic Acid Promoted Controllable Electrophilic Aromatic Nitration

“…Recently, the combination of HOTf and HFIP was found to be an effective system for electrophilic aromatic substitution reactions . We also applied this system to the electrophilic substitution reactions of carboranes and found that HOTf can increase the electrophilicity of the electrophilic reagent, so we wonder whether HOTf can be used in the electrophilic nitration of arenes, especially the electron-deficient arenes with the commercially available 68% HNO 3 as the electrophilic reagent. Through our endeavor, the nitration of various arenes was achieved with HOTf as the catalyst in HFIP or under solvent-free conditions (Scheme e).…”

“…On the basis of Hua’s work and our previous work, we initially examined the influence of Brønsted acids on the electrophilic nitration of benzene under 1 equiv of 68% HNO 3 in HFIP solvent (Table , entries 1–4). It was found that the addition of HOTf could greatly promote the reaction, and the best result was obtained when 50 mol % HOTf was used.…”

A strategy for regioselective B–H functionalization ofo-carboranesviabase metal catalysis

“…4 In this regard, effective and controlled functionalization of carboranes has therefore attracted enormous research interest, especially regioselective cage B–H derivatization among 10 similar B–H vertices. As a result, a large set of methods has been developed for the preparation of functionalized carboranes through three different strategies: electrophilic B–H substitution, 1,5 nucleophilic B–H substitution 6 and transition metal-catalyzed B–H functionalization. 7 In recent years, the Xie group has developed a general strategy for o -carborane cage B–H functionalization via transition metal catalysis (Fig.…”