The 1,3-dipolar cycloaddition between cyclooctynes and azides, termed �copper-free click chemistry,� has enabled the study of biomolecules in their native environments.  In these studies, the degree of labeling one can achieve is dependent on the intrinsic reactivity of the cyclooctyne.  As a result, a systematic method of predicting cyclooctyne reactivity is of interest, particularly in the design of new reagents.Here, we have analyzed the reactivity of a series of substituted biarylazacyclooctynone (BARAC) compounds both empirically and using a distortion/interaction DFT model.  In particular, we have focused on the effects of electronic perturbation through installation of electron withdrawing and donating groups, and have also analyzed the influence sterics via installation of bulky substituents.  Results, which indicate only minor reactivity changes through electronic perturbation but significant changes through steric interactions, suggest that the DFT distortion/interaction model is a useful predictor of cyclooctyne reactivity.

Reactivity of biarylazacyclooctynones (BARAC) in copper-free click chemistry

243rd National Meeting (2012)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.