10.1021/ja1081519.s001
Brian C. Sanders
Brian C.
Sanders
Frédéric Friscourt
Frédéric
Friscourt
Petr A. Ledin
Petr A.
Ledin
Ngalle Eric Mbua
Ngalle Eric
Mbua
Selvanathan Arumugam
Selvanathan
Arumugam
Jun Guo
Jun
Guo
Thomas J. Boltje
Thomas J.
Boltje
Vladimir V. Popik
Vladimir V.
Popik
Geert-Jan Boons
Geert-Jan
Boons
Metal-Free Sequential [3 + 2]-Dipolar Cycloadditions using Cyclooctynes and 1,3-Dipoles of Different Reactivity
American Chemical Society
2011
cycloaddition
azide
cyclooctyne
oxidation
material
oxime
nitrile oxides
procedure
diazocarbonyl derivatives
Cycloaddition
BAIB
2011-02-02 00:00:00
Journal contribution
https://acs.figshare.com/articles/journal_contribution/Metal_Free_Sequential_3_2_Dipolar_Cycloadditions_using_Cyclooctynes_and_1_3_Dipoles_of_Different_Reactivity/2695369
Although metal-free cycloadditions of cyclooctynes and azides to give stable 1,2,3-triazoles have found wide utility in chemical biology and material sciences, there is an urgent need for faster and more versatile bioorthogonal reactions. We have found that nitrile oxides and diazocarbonyl derivatives undergo facile 1,3-dipolar cycloadditions with cyclooctynes. Cycloadditions with diazocarbonyl derivatives exhibited similar kinetics as compared to azides, whereas the reaction rates of cycloadditions with nitrile oxides were much faster. Nitrile oxides could conveniently be prepared by direct oxidation of the corresponding oximes with BAIB, and these conditions made it possible to perform oxime formation, oxidation, and cycloaddition as a one-pot procedure. The methodology was employed to functionalize the anomeric center of carbohydrates with various tags. Furthermore, oximes and azides provide an orthogonal pair of functional groups for sequential metal-free click reactions, and this feature makes it possible to multifunctionalize biomolecules and materials by a simple synthetic procedure that does not require toxic metal catalysts.