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Catalytic Enantioselective Intramolecular C(sp 3 )−H Amination of 2‐Azidoacetamides
Author(s) -
Zhou Zijun,
Chen Shuming,
Qin Jie,
Nie Xin,
Zheng Xingwen,
Harms Klaus,
Riedel Radostan,
Houk K. N.,
Meggers Eric
Publication year - 2019
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201811927
Subject(s) - enantioselective synthesis , amination , intramolecular force , chemistry , catalysis , steric effects , ruthenium , amide , stereochemistry , medicinal chemistry , combinatorial chemistry , organic chemistry
An enantioselective ring‐closing C(sp 3 )−H amination of 2‐azidoacetamides is catalyzed by a chiral‐at‐metal ruthenium complex and provides chiral imidazolidin‐4‐ones in 31–95 % yield, with enantioselectivities of up to 95 % ee , and at catalyst loadings down to 0.1 mol % (turnover number (TON)=740). To our knowledge, this is the first example of a highly enantioselective C(sp 3 )−H amination with aliphatic azides. Mechanistic experiments reveal the importance of the amide group, which presumably enables initial bidentate coordination of the 2‐azidoacetamides to the catalyst. DFT calculations show that the transition state leading to the major enantiomer features a better steric fit and favorable π–π stacking between the substrate and the catalyst framework.