Formal nucleophilic pyrrolylmethylation via palladium-based auto-tandem catalysis: switchable regiodivergent synthesis and remote chirality transfer

Although nucleophilic benzylation-type reaction to introduce various aromatic systems into molecules has been widely explored, the related pyrrolylmethylation version remains to be disclosed. Reported herein is a palladium-catalysed multiple auto-tandem reaction between N-Ts propargylamines, allyl carbonates and aldimines in the presence of an acid, proceeding through sequential allylic amination, cycloisomerisation, vinylogous addition and aromatisation steps. A diversity of formal pyrrolylmethylated amine products were finally furnished efficiently. In addition, switchable regiodivergent 3-pyrrolylmethylation and 4-pyrrolylmethylation were realised by tuning catalytic conditions. Moreover, remote chirality transfer with readily available enantioenriched starting materials was well achieved with an achiral ligand, relying on diastereoselective generation of eta(2)-Pd(0) complexes between Pd(0) and chiral 1,3-diene intermediates in the key vinylogous addition step. A few control experiments were conducted to elucidate the palladium-involved tandem reaction and regiodivergent synthesis.

Automated summary

Herein, a palladium-catalysed multiple auto-tandem reaction for the efficient synthesis of formal pyrrolylmethylated amine products was reported. The regiodivergent selectivity could be switched by tuning the catalytic conditions. In addition, remote chirality transfer was achieved using an achiral ligand.