C(sp3)–H Methylation Enabled by Peroxide Photosensitization and Ni-Mediated Radical Coupling
Shannon Stahl reports on the C(sp3)–H methylation using a transition-metal catalyst and a peroxide-based oxidant.
Methylation of organic molecules is increasingly emerging as a very useful structural modification and biological pro-filing strategy in the rational design of bioactive compounds and drugs. In fact, a relatively subtle structural modification stemming from the introduction of a methyl group has the potential to strongly alter both pharmaco-dynamic and pharmaco-kinetic profiles of a drug candidate, as a consequence of changes in its stereo-electronic properties. According to Professor Shannon Stahl from the University of Wisconsin-Madison (USA), methylated building blocks are a staple of medicinal chemistry library designs. He explained that “when an amine building block is chosen to be included in a screening library, it is likely that various methylated analogues of that building block will also be evaluated, if they are commercially available. The introduction of a methyl group can significantly affect the properties of the resulting drug lead. There are cases where the installation of a methyl group results in thousand-fold improvements in potency or results in defining drops in toxicity.”