Despite the fact that nucleophilic displacement (S_N2) 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 sp³ C–N bonds at room temperature. The process provides S_N2-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.

尽管卤代烷与氮亲核试剂的亲核置换 (S _N 2) 是有机化学教学中最早引入的反应之一，但其实际应用在很大程度上仅限于不受阻碍的（初级）或活化的（α-羰基、苄基）底物. 在这里，我们展示了一种替代胺化策略，其中烷基碘被用作自由基前体而不是亲电子试剂。使用 α-氨基烷基自由基可以通过卤素原子转移将碘化物有效地转化为相应的烷基自由基，而铜催化在室温下组装sp ³ C-N 键。该过程提供 S _N2 样的可编程性以及在几种密集功能化药物的后期功能化中的应用证明了其在制备有价值的N-烷基化药物类似物方面的实用性。