Synthesis of Chiral Tetrahydro-3-benzazepine Motifs by Iridium-Catalyzed Asymmetric Hydrogenation of Cyclic Ene-carbamates

A highly efficient N,P-ligated iridium complex is presented for the simple preparation of chiral tetrahydro-3-benzazepine motifs by catalytic asymmetric hydrogenation. Substrates bearing both 1-aryl and 1-alkyl substituents were smoothly converted to the corresponding hydrogenated product with excellent enantioselectivity (91 99% ee) and in isolated yield (92-99%). The synthetic value of this transformation was demonstrated by a gram-scale hydrogenation and application in the syntheses of trepipam and fenoldopam.

Automated summary

A highly efficient N,P-ligated iridium complex was developed for the synthesis of chiral tetrahydro-3-benzazepine motifs through catalytic asymmetric hydrogenation. The method exhibited excellent enantioselectivity and high yield, and was successfully applied in the synthesis of pharmaceuticals.