Metal- and Oxidant-Free Direct sp3 CH Arylation of Pyrrolidine

Arylated aliphatic N‐heterocycles, and particularly arylated pyrrolidines, have a wide range of applications in medicine as well as in chemistry. Arylation of pyrrolidines mainly relies on metal‐mediated couplings, which produce unwanted toxic metal waste. In this Communication, we report an oxidant‐ and metal‐free method for direct sp3 CH arylation of pyrrolidine employing a highly atom economic three‐component reaction. The method, operating under very simple and mild conditions, is highly selective and very efficient in producing single regioisomer of the arylated product even on a multigram scale. As an alternative to the metal‐mediated reaction, this method has the potential to be used in production at an industrial scale. Moreover, a new approach for CH arylation based on a novel reactivity that differs from the reactivity in Mannich or Betti reactions of iminium ion is presented. Out of metal! A metal‐ and oxidant‐free method for direct sp3 CH arylation of pyrrolidine has been developed. As an alternative to metal‐mediated reactions, the method relies on a highly atom economic three‐component reaction, which is selective for single regioisomers of aryl pyrrolidines that are important in chemistry as well as in biology. The method, operating under simple and mild reaction conditions, is very efficient, even on a multigram scale.