Copper-catalysed amination of alkyl iodides enabled by halogen-atom transfer

Despite the fact that nucleophilic displacement (S N 2) of alkyl halides with nitrogen nucleophiles is one of the first reactions introduced in organic chemistry teaching, its practical utilization is largely limited to unhindered (primary) or activated (α-carbonyl, benzylic) substrates. Here, we demonstrate an alternative amination strategy where alkyl iodides are used as radical precursors instead of electrophiles. Use of α-aminoalkyl radicals enables the efficient conversion of the iodides into the corresponding alkyl radical by halogen-atom transfer, while copper catalysis assembles the sp 3 C–N bonds at room temperature. The process provides S N 2-like programmability, and application in late-stage functionalization of several densely functionalized pharmaceuticals demonstrates its utility in the preparation of valuable N -alkylated drug analogues.