Enantioselective Copper Catalyzed Alkyne–Azide Cycloaddition by Dynamic Kinetic Resolution

The copper­(I) catalyzed alkyne–azide cycloaddition (CuAAC), a click reaction, is one of the most powerful catalytic reactions developed during the last two decades. Conducting CuAAC enantioselectively would add a third dimension to this reaction and would enable the direct synthesis of α-chiral tri...

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Bibliographic Details
Published in:Journal of the American Chemical Society 2019-04, Vol.141 (13), p.5135-5138
Main Authors: Liu, En-Chih, Topczewski, Joseph J
Format: Article
Language:English
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Summary:The copper­(I) catalyzed alkyne–azide cycloaddition (CuAAC), a click reaction, is one of the most powerful catalytic reactions developed during the last two decades. Conducting CuAAC enantioselectively would add a third dimension to this reaction and would enable the direct synthesis of α-chiral triazoles. Doing so is demanding because the two precursors have linear geometries, and the triazole product is a flat heterocycle. Designing a chiral catalyst is further complicated by the complex mechanism of CuAAC. We report an enantioselective CuAAC (E-CuAAC), enabled by dynamic kinetic resolution (DKR). The E-CuAAC is high yielding and affords up to 99:1 er. The E-CuAAC can directly generate α-chiral triazoles in a complex molecular environment.
ISSN:0002-7863
1520-5126
DOI:10.1021/jacs.9b01091