Site Selective Chlorination of C(sp3)−H Bonds Suitable for Late‐Stage Functionalization

C(sp3)−Cl bonds are present in numerous biologically active small molecules, and an ideal route for their preparation is by the chlorination of a C(sp3)−H bond. However, most current methods for the chlorination of C(sp3)−H bonds are insufficiently site selective and tolerant of functional groups to be applicable to the late‐stage functionalization of complex molecules. We report a method for the highly selective chlorination of tertiary and benzylic C(sp3)−H bonds to produce the corresponding chlorides, generally in high yields. The reaction occurs with a mixture of an azidoiodinane, which generates a selective H‐atom or under mild conditions, and a readily‐accessible and inexpensive copper(II) chloride complex, which efficiently transfers a chlorine atom. The reaction's exceptional functional group tolerance is demonstrated by the chlorination of >30 diversely functionalized substrates and the late‐stage chlorination of a dozen derivatives of natural products and active pharmaceutical ingredients. Existing methods for the chlorination of C(sp3)−H bonds occur with low site‐selectivity and tolerance for functional groups. We report a highly selective chlorination of C(sp3)−H bonds suitable for the late‐stage functionalization of natural products and active pharmaceutical ingredients by a reaction design that separates the components ing the H‐atom (an azidoiodinane) and transferring the chlorine atom (a copper(II) chloride complex).