Synthesis of Functionalized Isoquinolone Derivatives via Rh(III)-Catalyzed [4+2]-Annulation of Benzamides with Internal Acetylene-Containing α-CF3-α-Amino Carboxylates

A convenient pathway to a new series of alpha-CF3-substituted alpha-amino acid derivatives bearing pharmacophore isoquinolone core in their backbone has been developed. The method is based on [4+2]-annulation of N-(pivaloyloxy) aryl amides with orthogonally protected internal acetylene-containing alpha-amino carboxylates under Rh(III)-catalysis. The target annulation products can be easily transformed into valuable isoquinoline derivatives via a successive aromatization/cross-coupling operation.

Automated summary

A convenient method has been developed for the synthesis of a new series of alpha-CF3-substituted alpha-amino acid derivatives bearing pharmacophore isoquinolone core. The method involves the [4+2]-annulation of N-(pivaloyloxy) aryl amides with orthogonally protected internal acetylene-containing alpha-amino carboxylates under Rh(III)-catalysis. The resulting annulation products can be easily transformed into valuable isoquinoline derivatives through a successive aromatization/cross-coupling operation.