Work

Bioorthogonal Hydroamination of Push–Pull‐Activated Linear Alkynes

Year: 2021

Type: article

Abstract: A bioorthogonal reaction between N,N-dialkylhydroxylamines and push-pull-activated halogenated alkynes is described. We explore the use of rehybridization effects in activating alkynes, and we show that electronic effects, when competing stereoelectronic and inductive factors are properly balanced, sufficiently activate a linear alkyne in the uncatalyzed conjugative retro-Cope elimination reaction while adequately protecting it against cellular nucleophiles. This design preserves the low steric profile of an alkyne and pairs it with a comparably unobtrusive hydroxylamine. The kinetics are on par with those of the fastest strain-promoted azide-alkyne cycloaddition reactions, the products regioselectively formed, the components sufficiently stable and easily installed, and the reaction suitable for cellular labeling.

Source: Angewandte Chemie International Edition

DOI: 10.1002/anie.202104863

Authors: Dahye Kang, Sheldon T. Cheung, Justin Kim

Institutions: Harvard University, Dana-Farber Cancer Institute

Language: English

Topic: Click Chemistry and Applications

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: green

Funder: National Institute of Environmental Health Sciences

Award: Post-Translational Modification of Protein Surfaces