Wei Haipeng, Luo Yicong, Ren Jinbao, Yuan Qianjia, Zhang Wanbin
Shanghai Key Laboratory of Molecular Engineering of Chiral Drugs, Frontiers Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, 200240, Shanghai, P. R. China.
Nat Commun. 2024 Oct 10;15(1):8775. doi: 10.1038/s41467-024-53005-x.
Chiral tertiary alcohols are an important structural motif, however, the general and efficient methodologies for their synthesis are less reported. Herein, we report a Ni(ІІ)-catalyzed asymmetric alkenylation and arylation of aryl ketones with organoborons under air via a 1,5-metalate shift strategy to obtain chiral tertiary allylic alcohols and diaryl alcohols. The reaction demonstrates good functional group tolerance and delivers chiral tertiary alcohols with good to excellent results. Furthermore, this method can be applied to the late-stage modification of drugs and the efficient synthesis of natural products. Notably, the reaction proceeds through an outer-sphere mechanism. The Ni(II) complex functions both as a Lewis acid to activate the ketone and create a chiral environment, and as coordination bridge linking the ketone and the organoboron-derived "ate" complex, facilitating the 1,5-metalate shift without forming a C-Ni bond. This approach contrasts with traditional transition metal-catalyzed nucleophilic addition reactions that involve carbon-metal bond formation.
手性叔醇是一种重要的结构单元，然而，关于其合成的通用且高效的方法报道较少。在此，我们报道了一种镍（II）催化的芳基酮与有机硼在空气中通过1,5-金属迁移策略进行的不对称烯基化和芳基化反应，以获得手性叔烯丙醇和二芳基醇。该反应表现出良好的官能团耐受性，并能以良好至优异的结果得到手性叔醇。此外，该方法可应用于药物的后期修饰和天然产物的高效合成。值得注意的是，该反应通过外层球机制进行。镍（II）配合物既作为路易斯酸活化酮并创造手性环境，又作为连接酮和有机硼衍生的“酸根”配合物的配位桥，促进1,5-金属迁移而不形成碳-镍键。这种方法与涉及碳-金属键形成的传统过渡金属催化的亲核加成反应形成对比。
