Gong Yi, Wang Cai, Zhou Feng, Liao Kui, Wang Xi-Yu, Sun Ying, Zhang Yan-Xue, Tu Zhi, Wang Xin, Zhou Jian
Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, Shanghai Key Laboratory of Green Chemistry and Chemical Processes, School of Chemistry and Molecular Engineering, East China Normal University, 3663 N Zhongshan Road, Shanghai, 200062, China.
College of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang, 550025, P. R. China.
Angew Chem Int Ed Engl. 2023 Apr 24;62(18):e202301470. doi: 10.1002/anie.202301470. Epub 2023 Mar 24.
We report the first highly selective kinetic resolution of racemic α-chiral azides via Cu-catalyzed azide-alkyne cycloaddition (CuAAC). Newly developed pyridine-bisoxazoline (PYBOX) ligands, bearing a C4 sulfonyl group, enable effective kinetic resolution of racemic azides derived from privileged scaffolds such as indanone, cyclopentenone, and oxindole, and their asymmetric CuAAC to afford α-tertiary 1,2,3-triazoles with high to excellent ee values. DFT calculations and control experiments reveal that the C4 sulfonyl group decreases the Lewis basicity of the ligand and increases the electrophilicity of the copper center for better recognition of azides, and functions as a shielding group to make the chiral pocket of the catalyst more effective.
我们报道了首例通过铜催化的叠氮化物-炔烃环加成反应（CuAAC）对消旋α-手性叠氮化物进行的高选择性动力学拆分。新开发的带有C4磺酰基的吡啶-双恶唑啉（PYBOX）配体能够有效地对源自茚满酮、环戊烯酮和氧化吲哚等优势骨架的消旋叠氮化物进行动力学拆分，并实现其不对称CuAAC反应，以提供具有高至优异对映体过量（ee）值的α-叔基1,2,3-三唑。密度泛函理论（DFT）计算和对照实验表明，C4磺酰基降低了配体的路易斯碱性，并增加了铜中心的亲电性，从而更好地识别叠氮化物，并且作为一个屏蔽基团使催化剂的手性口袋更有效。
