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Oxidative Amide Coupling from Functionally Diverse Alcohols and Amines Using Aerobic Copper/Nitroxyl Catalysis
Author(s) -
Piszel Paige E.,
Vasilopoulos Aristidis,
Stahl Shan S.
Publication year - 2019
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201906130
Subject(s) - chemistry , amide , stereocenter , catalysis , reactivity (psychology) , steric effects , nitroxyl , oxidative coupling of methane , amination , alcohol oxidation , nonane , primary (astronomy) , combinatorial chemistry , organic chemistry , oxidative phosphorylation , enantioselective synthesis , medicine , physics , alternative medicine , pathology , astronomy , biochemistry
Abstract The aerobic Cu/ABNO catalyzed oxidative coupling of alcohols and amines is highlighted in the synthesis of amide bonds in diverse drug‐like molecules (ABNO=9‐azabicyclo[3.3.1]nonane N ‐oxyl). The robust method leverages the privileged reactivity of alcohols bearing electronegative hetero‐ atoms (O, F, N, Cl) in the β‐position. The reaction tolerates over 20 unique functional groups and is demonstrated on a 15 mmol scale under air. Steric constraints of the catalyst allow for chemoselective amidation of primary amines in the presence of secondary amines. All catalyst components are commercially available, and the reaction proceeds under mild conditions with retention of stereocenters in both reaction partners, while producing only water as a by‐product.