Diazo compounds as highly tunable reactants in 1,3-dipolar cycloaddition reactions with cycloalkynesElectronic supplementary information (ESI) available: Experimental procedures, computational data, and spectral data for novel compounds. See DOI: 10.1039/c2sc20806g

• Main Authors: McGrath, Nicholas A, Raines, Ronald T
• Format: Article
• Language: English
• ISSN: 2041-6520; 2041-6539
• DOI: 10.1039/c2sc20806g

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. 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.