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A Modified System for the Synthesis of Enantioenriched N ‐Arylamines through Copper‐Catalyzed Hydroamination
Author(s) -
Ichikawa Saki,
Zhu Shaolin,
Buchwald Stephen L.
Publication year - 2018
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201803026
Subject(s) - hydroamination , enantioselective synthesis , chemistry , electrophile , catalysis , copper , combinatorial chemistry , organic chemistry , yield (engineering) , hydride , metal , materials science , metallurgy
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.