Enantioselective Nickel-Catalyzed Alkyne–Azide Cycloaddition by Dynamic Kinetic Resolution
- 2 April 2021
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of the American Chemical Society
- Vol. 143 (14), 5308-5313
- https://doi.org/10.1021/jacs.1c01354
Abstract
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.Keywords
Funding Information
- NIH-NIGMS (R35GM124718, S10OD011952)
This publication has 71 references indexed in Scilit:
- Zn/C‐Catalyzed Cycloaddition of Azides and Aryl AlkynesEuropean Journal of Organic Chemistry, 2010
- Copper-catalyzed azide–alkyne cycloaddition (CuAAC) and beyond: new reactivity of copper(i) acetylidesChemical Society Reviews, 2010
- Analysis and Optimization of Copper‐Catalyzed Azide–Alkyne Cycloaddition for BioconjugationAngewandte Chemie, 2009
- Copper(I)‐Catalyzed Cycloaddition of Organic Azides and 1‐IodoalkynesAngewandte Chemie, 2009
- Bioorthogonal Chemistry: Fishing for Selectivity in a Sea of FunctionalityAngewandte Chemie, 2009
- ‘Click’ Chemistry in Polymer and Material Science: An UpdateMacromolecular Rapid Communications, 2008
- Ruthenium-Catalyzed Cycloaddition of Alkynes and Organic AzidesJournal of the American Chemical Society, 2005
- Click chemistry in materials synthesis. 1. Adhesive polymers from copper‐catalyzed azide‐alkyne cycloadditionJournal of Polymer Science Part A: Polymer Chemistry, 2004
- A Stepwise Huisgen Cycloaddition Process: Copper(I)-Catalyzed Regioselective “Ligation” of Azides and Terminal AlkynesAngewandte Chemie, 2002
- REARRANGEMENT OF ALLYLIC AZIDESJournal of the American Chemical Society, 1960