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A Modified System for the Synthesis of Enantioenriched N-Arylamines through Copper-Catalyzed Hydroamination.

ABSTRACT: Despite significant recent progress in copper-catalyzed enantioselective hydroamination chemistry, the synthesis of chiral N-arylamines, which are frequently found in natural products and pharmaceuticals, has not been realized. Initial experiments with N-arylhydroxylamine ester electrophiles were unsuccessful and, instead, their reduction in the presence of copper hydride (CuH) catalysts was observed. Herein, we report key modifications to our previously reported hydroamination methods that lead to broadly applicable conditions for the enantioselective net addition of secondary anilines across the double bond of styrenes, 1,1-disubstituted olefins, and terminal alkenes. NMR studies suggest that suppression of the undesired reduction pathway is the basis for the dramatic improvements in yield under the reported method.

SUBMITTER: Ichikawa S

PROVIDER: S-EPMC6033674 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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A Modified System for the Synthesis of Enantioenriched N-Arylamines through Copper-Catalyzed Hydroamination.

Ichikawa Saki S Zhu Shaolin S Buchwald Stephen L SL

Angewandte Chemie (International ed. in English) 20180612 28

Despite significant recent progress in copper-catalyzed enantioselective hydroamination chemistry, the synthesis of chiral N-arylamines, which are frequently found in natural products and pharmaceuticals, has not been realized. Initial experiments with N-arylhydroxylamine ester electrophiles were unsuccessful and, instead, their reduction in the presence of copper hydride (CuH) catalysts was observed. Herein, we report key modifications to our previously reported hydroamination methods that lead ...[more]

PMID: 29847002

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