在该研究中，研究组提出合成B(9)-OH-o-碳硼烷的一种化学稳定和高效的合成路线，即用商品化68%硝酸溶液，在三氟甲基磺酸（HOTf）和六氟异丙醇（HFIP）的辅助下氧化o-碳硼烷。该反应对宽范围的碳硼烷都具有较高效率，且B(9)和B(8)的选择性达到98:2。这一反应的成功依赖于硝酸强大的亲电性和氧化性能，通过HOTf这种Bronsted酸和碳硼烷之间的氢键得以加强。
机制研究表明，o-碳硼烷的氧化涉及硝酸对o-碳硼烷电负性最强的氢原子的初始亲电攻击。在这个变化中，B-H键的氢原子是亲核位点，这与亲电取代反应中硼原子是亲核位点有所区别。因此，这是一个在温和的条件下N (V)→N (III)和H(-I)→H(I)的氧化还原反应。研究人员还对9-OH-o-碳硼烷进行了衍生化，其碳硼羰基位点被成功接入一种氨基酸、聚乙二醇、生物素、脱氧尿苷和糖类。毫无疑问，这种方法提供了一种选择性对碳硼烷的快速接入小分子的方式，用在需要实现靶向递送富硼基团，诸如硼中子捕获治疗中。
附：英文原文
Title: B(9)-OH-o-Carboranes: Synthesis, Mechanism, and Property Exploration
Author: Yan-Na Ma, Huazhan Ren, Yanxuan Wu, Na Li, Feijing Chen, Xuenian Chen
Issue&Volume: March 24, 2023
Abstract: 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 Brnsted 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.
DOI: 10.1021/jacs.2c13570
