Organocatalytic Atroposelective Synthesis of Isoquinolines via Dynamic Kinetic Resolution

Herein, a highly enantioselective Pictet-Spengler react on for the synthesis of axially chiral tetrahydroisoquinolines via dynamic kinetic resolution is described. Chiral phosphoric acids catalyze cyclization to yield single regioisomeric isoquinolines with excellent enantioselectivities around the C-C bond up to 99% ee. The current protocol is effective for a wide range of substrates, and the observed enantiodivergence depends on the substituents on the catalysts.

Automated summary

In this study, a highly enantioselective Pictet-Spengler reaction for the synthesis of axially chiral tetrahydroisoquinolines via dynamic kinetic resolution is reported. The cyclization catalyzed by chiral phosphoric acids leads to the formation of single regioisomeric isoquinolines with excellent enantioselectivities up to 99% ee around the C-C bond. The effectiveness of this protocol is demonstrated for a wide range of substrates, with enantiodivergence observed depending on the substituents on the catalysts.