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

Angewandte Chemie
Saki IchikawaStephen L Buchwald

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.

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Citations

Jan 17, 2019·Chemistry : a European Journal·Juan-Juan Wang, Wei Yu
Jan 20, 2019·Angewandte Chemie·Xi-Jie DaiStephen L Buchwald
Apr 4, 2019·Chemistry : a European Journal·Shona BanjoNoritaka Chida
Jun 5, 2021·Chemical Record : an Official Publication of the Chemical Society of Japan ... [et Al.]·Jinwon JeonSungwoo Hong
Nov 19, 2020·Journal of the American Chemical Society·Jinwon JeonSungwoo Hong
Jun 12, 2019·Chemical Reviews·Katerina M Korch, Donald A Watson
May 14, 2020·Accounts of Chemical Research·Richard Y Liu, Stephen L Buchwald
Aug 25, 2021·The Journal of Organic Chemistry·Yang GaoXiao-Qiang Hu
Oct 19, 2019·Organic Letters·Saki Ichikawa, Stephen L Buchwald

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