Chiral Indolizidine Synthesis through the Ir-Catalyzed Asymmetric Hydrogenation of Cyclic Pyridinium Salts

The Ir-catalyzed asymmetric hydrogenation of cyclic pyridinium salts is presented as a new strategy for the convenient and efficient synthesis of chiral indolizidines. The asymmetric hydrogenation of cyclic pyridinium salts derived from 2-(2-acylphenyl)-pyridines proceeded smoothly in the presence of [Ir(cod)Cl](2) and (R)-DM-SegPhos to provide the desired chiral 7,8-benzoindolizidines 6 in high to excellent yields with moderate enantioselectivity (up to 86:14 er) and excellent diastereoselectivity (>20:1 dr). The enantiomeric purity of 6j was increased to 92:8 through recrystallization.

Automated summary

The study demonstrates a new strategy for the synthesis of chiral indolizidines through Ir-catalyzed asymmetric hydrogenation of cyclic pyridinium salts. The desired chiral products were obtained with high to excellent yields, moderate enantioselectivity, and excellent diastereoselectivity. The enantiomeric purity of the product was improved through recrystallization.