Aliphatic C–H bonds yield to arylation

Abstract

While many chemistries have been developed to incite C–H bonds to react, certain types of aliphatics stubbornly resist such transformations. Now, chemists at Princeton University and Merck & Co. have come up with a dual-catalyst reaction that activates aliphatics with recalcitrant C–H bonds, provoking them to react with aryl bromides. The finding opens new avenues for medicinal chemists, who are always on the lookout for reactions that give them the ability to add complexity to existing drug candidates quickly and easily, says Princeton’s David W. C. MacMillan, who led the research. The reaction will allow medicinal chemists to tweak a compound to improve its properties or to prepare a series of similar compounds to compare how structural modifications alter their activity. The reaction combines light-driven, polyoxometalate-facilitated hydrogen atom transfer and nickel catalysis (Nature 2018, DOI: 10.1038/s41586-018-0366-x). A decatungstate catalyst generates carbon-centered radicals from strong, neutral...