Diazo Compounds as Highly Tunable Reactants in 1,3-Dipolar Cycloaddition Reactions with Cycloalkynes()

Chem Sci. 2012 Jan 1;3(11):3237-3240. doi: 10.1039/C2SC20806G. Epub 2012 Aug 2.


Diazo compounds, which can be accessed directly from azides by deimidogenation, are shown to be extremely versatile dipoles in 1,3-dipolar cycloaddition reactions with a cyclooctyne. The reactivity of a diazo compound can be much greater or much less than its azide analog, and is enhanced markedly in polar-protic solvents. These reactivities are predictable from frontier molecular orbital energies. The most reactive diazo compound exhibited the highest known second-order rate constant to date for a dipolar cycloaddition with a cycloalkyne. These data provide a new modality for effecting chemoselective reactions in a biological context.