Xu Hong-Lei, Zhu Minghui, Sung Herman H Y, Williams Ian D, Lin Zhenyang, Zhang Chaoshen, Sun Jianwei
Department of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR 999077, China.
The Hong Kong Branch of Chinese National Engineering Research Centre for Tissue Restoration & Reconstruction, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR 999077, China.
J Am Chem Soc. 2025 Jan 29;147(4):3692-3701. doi: 10.1021/jacs.4c16062. Epub 2025 Jan 14.
Carboranyl amines are distinct from typical organic amines. Due to the electronic influence of the carborane cage, they have low nucleophilicity and are reluctant to alkylate. Moreover, asymmetric synthesis of chiral carboranes is still in its infancy. Herein we have achieved the first catalytic asymmetric -alkylation of -carboranyl amine, providing general access to diverse secondary -carboranyl amines with high efficiency and enantioselectivity under mild conditions. For the first time, asymmetric organocatalysis was introduced to carborane chemistry. Key to the success is the use of generated (naphtho-)quinone methides as the alkylating reagents and suitable chiral acid catalysts. This protocol is also applicable to the asymmetric -alkylation of 1-SH--CBH. Control experiments and kinetic studies provided important insights into the reaction mechanism, which likely involves rate-determining generation of the quinone methide followed by fast and enantio-determining nucleophilic addition.
碳硼烷胺与典型的有机胺不同。由于碳硼烷笼的电子效应，它们的亲核性较低，且不易发生烷基化反应。此外，手性碳硼烷的不对称合成仍处于起步阶段。在此，我们实现了首例碳硼烷胺的催化不对称α-烷基化反应，在温和条件下高效且对映选择性地提供了多种仲碳硼烷胺。首次将不对称有机催化引入碳硼烷化学领域。成功的关键在于使用生成的（萘）醌甲基化物作为烷基化试剂以及合适的手性酸催化剂。该方法也适用于1-SH-1-CBH的不对称α-烷基化反应。对照实验和动力学研究为反应机理提供了重要见解，该反应机理可能涉及醌甲基化物的速率决定生成过程，随后是快速且决定对映体选择性的亲核加成反应。
