Open AccessEnantioselective Nickel-Catalyzed Alkyne–Azide Cycloaddition by Dynamic Kinetic Resolution
Author(s) -
En-Chih Liu,
Joseph J. Topczewski
Publication year - 2021
Publication title -
journal of the american chemical society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.115
H-Index - 612
eISSN - 1520-5126
pISSN - 0002-7863
DOI - 10.1021/jacs.1c01354
Subject(s) - chemistry , enantioselective synthesis , cycloaddition , kinetic resolution , azide , alkyne , combinatorial chemistry , allylic rearrangement , catalysis , triazole , amide , stereochemistry , organic chemistry
The triazole heterocycle has been widely adopted as an isostere for the amide bond. Many native amides are α-chiral, being derived from amino acids. This makes α- N -chiral triazoles attractive building blocks. This report describes the first enantioselective triazole synthesis that proceeds via nickel-catalyzed alkyne-azide cycloaddition (NiAAC). This dynamic kinetic resolution is enabled by a spontaneous [3,3]-sigmatropic rearrangement of the allylic azide. The 1,4,5-trisubstituted triazole products, derived from internal alkynes, are complementary to those commonly obtained by the related CuAAC reaction. Initial mechanistic experiments indicate that the NiAAC reaction proceeds through a monometallic Ni complex, which is distinct from the CuAAC manifold.