C(sp3)-H methylation enabled by peroxide photosensitization and Ni-mediated radical coupling

We report a synthetic method that enables direct methylation of C(sp3)–H bonds in diverse drug-like molecules and pharmaceutical building blocks. Visible light–initiated triplet energy transfer promotes homolysis of the O–O bond in di-tert-butyl or dicumyl peroxide under mild conditions. The resulting alkoxyl radicals undergo divergent reactivity, either hydrogen-atom transfer from a substrate C–H bond or generation of a methyl radical via β-methyl scission. The relative rates of these steps may be tuned by varying the reaction conditions or peroxide substituents to optimize the yield of methylated product arising from nickel-mediated cross-coupling of substrate and methyl radicals.

Source: ScienceNOW - April 22, 2021 Category: Science Authors: Vasilopoulos, A., Krska, S. W., Stahl, S. S. Tags: Chemistry reports Source Type: news