Reddy G Surendra, Reddy L Mallikarjuna, Kumar A Suresh, Ramachary Dhevalapally B
Catalysis Laboratory, School of Chemistry, University of Hyderabad, Hyderabad 500 046, India.
J Org Chem. 2020 Dec 4;85(23):15488-15501. doi: 10.1021/acs.joc.0c02247. Epub 2020 Nov 16.
An organocatalytic azide-ketone [3 + 2] cycloaddition (OrgAKC) of a variety of 1-aryl-3-(arylthio)propan-2-ones and 1-alkyl-3-(arylthio)propan-2-ones with different aryl/vinyl/alkyl azides is reported under ambient conditions to furnish the medicinally important 1,4-disubstituted-5-arylthiomethyl-1,2,3-triazoles and 1,5-disubstituted-4-arylthio-1,2,3-triazoles, respectively, in a regioselective manner with high yields/rates. With controlled and online NMR experiments, we proved that the reaction path is following the organocatalytic enolization through selective deprotonation followed by a [1,3]-H shift. Surprisingly, the [3 + 2] cycloaddition of aryl/vinyl/alkyl azides with the -generated equilibrated thermodynamic ↔ kinetic enolates furnished the highly regioselective functionally rich 1,2,3-triazoles by discriminating their reactivities. This is the first report on the investigation of a selective OrgAKC with the regiomers of enolates generated from the unsymmetrical carbonyl compounds. The reaction sustainability is explained with a few controlled experiments, mechanistic studies, and applications.
据报道，在环境条件下，多种1-芳基-3-(芳硫基)丙-2-酮和1-烷基-3-(芳硫基)丙-2-酮与不同的芳基/乙烯基/烷基叠氮化物发生有机催化的叠氮化物-酮[3 + 2]环加成反应（OrgAKC），分别以区域选择性的方式高产率/高速度地得到具有药用价值的1,4-二取代-5-芳硫基甲基-1,2,3-三唑和1,5-二取代-4-芳硫基-1,2,3-三唑。通过可控的在线核磁共振实验，我们证明反应路径是通过选择性去质子化进行有机催化烯醇化，随后发生[1,3]-H迁移。令人惊讶的是，芳基/乙烯基/烷基叠氮化物与生成的平衡热力学↔动力学烯醇盐的[3 + 2]环加成反应通过区分它们的反应活性，得到了区域选择性高、功能丰富的1,2,3-三唑。这是关于对由不对称羰基化合物生成的烯醇盐区域异构体进行选择性OrgAKC研究的首次报道。通过一些可控实验、机理研究和应用对反应的可持续性进行了解释。
