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Multigram Synthesis of a Chiral Substituted Indoline Via Copper-Catalyzed Alkene Aminooxygenation.

ABSTRACT: (S)-5-Fluoro-2-(2,2,6,6-tetramethylpiperidin-1-yloxymethyl)-1-tosylindoline, a 2-methyleneoxy-substituted chiral indoline, was synthesized on multigram scale using an efficient copper-catalyzed enantioselective intramolecular alkene aminooxygenation. The synthesis is accomplished in four steps and the indoline is obtained in 89% ee (>98% after one recrystallization). Other highlights include efficient gram-scale synthesis of the (4R,5S)-di-Ph-box ligand and efficient separation of a monoallylaniline from its bis(allyl)aniline by-product by distillation under reduced pressure.

SUBMITTER: Sequeira FC

PROVIDER: S-EPMC3358786 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature

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Multigram Synthesis of a Chiral Substituted Indoline Via Copper-Catalyzed Alkene Aminooxygenation.

Sequeira Fatima C FC Bovino Michael T MT Chipre Anthony J AJ Chemler Sherry R SR

Synthesis 20120422 10

(S)-5-Fluoro-2-(2,2,6,6-tetramethylpiperidin-1-yloxymethyl)-1-tosylindoline, a 2-methyleneoxy-substituted chiral indoline, was synthesized on multigram scale using an efficient copper-catalyzed enantioselective intramolecular alkene aminooxygenation. The synthesis is accomplished in four steps and the indoline is obtained in 89% ee (>98% after one recrystallization). Other highlights include efficient gram-scale synthesis of the (4R,5S)-di-Ph-box ligand and efficient separation of a monoallylani ...[more]

PMID: 22639473

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