1383435-90-2Relevant academic research and scientific papers
C(sp3)-H methylation enabled by peroxide photosensitization and Ni-mediated radical coupling
Vasilopoulos, Aristidis,Krska, Shane W.,Stahl, Shannon S.
, p. 398 - 403 (2021/05/06)
The “magic methyl” effect describes the change in potency, selectivity, and/or metabolic stability of a drug candidate associated with addition of a single methyl group. 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 b-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.
Nickel-catalyzed reductive coupling of aryl halides with secondary alkyl bromides and allylic acetate
Wang, Shulin,Qian, Qun,Gong, Hegui
supporting information; experimental part, p. 3352 - 3355 (2012/08/08)
A room-temperature Ni-catalyzed reductive method for the coupling of aryl bromides with secondary alkyl bromides has been developed, providing C(sp 2)-C(sp3) products in good to excellent yields. Slight modification of this protocol allows efficient coupling of activated aryl chlorides with cyclohexyl bromide and aryl bromides with allylic acetate.
