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

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-l-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-if) 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%). (C) 2016 Elsevier B.V. All rights reserved.