Ru-catalyzed C-H functionalization of phenylglycine derivatives: Synthesis of isoquinoline-1-carboxylates and isoindoline-1-carboxylates

Abstract The reaction of N -unprotected methylesters of phenylglycine derivatives ( 1a–1f ) with electron-rich internal alkynes ( 2a–2e ), catalyzed by [Ru(cymene)Cl 2 ] 2 (10%), gives the corresponding 3,4-disubstituted isoquinoline-1-carboxylates 3 through C H/N H oxidative coupling. The C H bond activation step is assisted by carboxylates, and N-fluoro-2,4,6-trimethylpyridinium triflate works as the terminal oxidant. The process shows a remarkable tolerance to the presence of diverse electron-releasing and electron-attracting functional groups at the phenyl ring of the amino acid. In addition, the reaction of phenylglycine derivatives ( 1a–1f ) with methyl acrylate ( 4a ) catalyzed by [Ru(cymene)Cl 2 ] 2 (10%) under the same experimental conditions, gives the corresponding 3, N -disubstituted isoindoline-1-carboxylates 5 through C H/N H coupling. Isoindolines 5 are obtained as a mixture of diastereoisomers, with moderate to high values of diastereomeric excess (up to 80%).