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An efficient iodide ion (I−)-enabled method for direct α-C(sp3)–H triazolization of ethers via a radical cross-coupling has been developed for regioselective construction of N2-substituted hemiaminal ethers. The developed C(sp3)–H triazolization reaction features the resulting products in good yields (up to 90%) and an excellent functional group tolerance to various ethers, including cyclic and linear ethers. Preliminary mechanistic study and DFT calculation investigation indicate that the reaction proceeds via a SN2-like desulfonylation radical coupling process and an (I−)-involved ternary complex is responsible for the high conversion ratio and the high regioselectivity. I− not only promotes the process but also prevents the in situ generated carbon-centered radicals (CCRs) from being oxidized into carbon cations in an oxidative environment. [ABSTRACT FROM AUTHOR]

Both isoindolinones and continuous quaternary carbons play important roles in pharmaceutical scaffolds. However, few examples have been developed to construct isoindolinones containing continuous quaternary carbons due to the steric hindrance effect. Here, a rhodium(II)-catalyzed reaction of 3-hydroxyisoindolinones and diazos via an intermolecular OH transfer to deliver the isoindolinone derivatives containing continuous quaternary carbons as products is developed in high yields of up to 89% via an intermolecular OH transfer with a green chemistry metric E-factor of 5.70. The resulting products exhibit antiviral activity against SARS-CoV-2 3CL protease (3CLpro) and control investigations show that the quaternary carbons and hydroxyl group are essential for the bioactivity. [ABSTRACT FROM AUTHOR]

A visible-light-induced highly efficient C(sp 3 )-H amination of ethers with amides and azoles has been presented under mild conditions via a nitrogen- and carbon-centered radical coupling process. This protocol successfully utilizes 2,3-dichloro-5,6-dicyano- p -benzoquinone (DDQ) and tert -butyl nitrite (TBN) as cocatalysts to deliver the aminated products of ethers under aerobic conditions. Notably, the developed reaction features the corresponding products in good yields (up to 93%) with a wide substrate scope. The mechanistic study indicates that C-N bond formation proceeds via a direct radical cross-coupling process. Preliminary biological activity analysis indicates that the resulting products have good and selective inhibitory activity on osteosarcoma (OS) cell lines and are promising for use as hits for drug discovery.