Catalytic enantioselective intramolecular hydroamination of alkenes using chiral aprotic cyclic urea ligand on manganese (II)

Asymmetric catalysis for enantioselective intramolecular hydroamination of alkenes is a critical method in the construction of enantioenriched nitrogen-containing rings, often prevalent in biologically active compounds and natural products. Herein, we demonstrate a facile enantioselective intramolecular hydroamination of alkenes for the synthesis of chiral pyrrolidine, piperidine, and indoline moieties, using a manganese (II) chiral aprotic cyclic urea catalyst. The cyclic ligand hinders the inversion of the N atom of the urea and effectively discriminate between the enantiomers of substrates. High-resolution mass spectrometry, deuterium labeling experiments, and molecular orbital energy analysis clearly reveal the intermediates and mechanism of the transformation. As a key step, oxygen coordination by chiral aprotic urea presents a robust control over the asymmetric intra-HA reaction through the involvement of a convergent assembly of two vital intermediates (Mn-N and C-Mn-Br), providing access to chiral cyclic amine systems in high yields with excellent enantioselectivity. Nitrogen-containing rings containing chiral carbon centers are a staple of bioactive molecules and natural products of interest, and synthetic methodologies for their development are a continual focus of organic chemists. Here, the authors disclose a protocol for the synthesis of enantioenriched saturated azacycles, via intramolecular hydroamination of alkenes, using a chiral cyclic urea ligand with manganese.