Premium
Bioorthogonal Hydroamination of Push–Pull‐Activated Linear Alkynes
Author(s) -
Kang Dahye,
Cheung Sheldon T.,
Kim Justin
Publication year - 2021
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202104863
Subject(s) - bioorthogonal chemistry , alkyne , chemistry , steric effects , hydroamination , hydroxylamine , combinatorial chemistry , nucleophile , cycloaddition , azide , click chemistry , catalysis , stereochemistry , organic chemistry
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.