Remote Site‐Selective Radical C(sp<sup>3</sup>)−H Monodeuteration of Amides using D<sub>2</sub>O
Lin Wang, Yong Xia, Volker Derdau, Armido Studer
Abstract
Abstract Site‐selective incorporation of deuterium into biologically active compounds is of high interest in pharmaceutical industry. We present a mild and environmentally benign metal‐free method for the remote selective radical C−H monodeuteration of aliphatic C−H bonds in various amides with inexpensive heavy water (D 2 O) as the deuterium source. The method uses the easily installed N‐allylsulfonyl moiety as an N‐radical precursor that generates the remote C‐radical via site‐selective 1,5‐ or 1,6‐hydrogen atom transfer (HAT). Methyl thioglycolate, that readily exchanges its proton with D 2 O, serves as the radical deuteration reagent and as a chain‐carrier. The highly site‐selective monodeuteration has been applied to different types of unactivated sp 3 ‐C−H bonds and also to the deuteration of C−H bonds next to heteroatoms. The potential utility of this method is further demonstrated by the site‐selective incorporation of deuterium into natural product derivatives and drugs.