Acceleration of 1,3-Dipolar Cycloadditions by Integration of Strain and Electronic Tuning.

ABSTRACT: The 1,3-dipolar cycloaddition between azides and alkynes provides new means to probe and control biological processes. A major challenge is to achieve high reaction rates with stable reagents. The optimization of alkynyl reagents has relied on two strategies: increasing strain and tuning electronics. We report on the integration of these strategies. A computational analysis suggested that a CH → N aryl substitution in dibenzocyclooctyne (DIBO) could be beneficial. In transition states, the nitrogen of 2-azabenzo-benzocyclooctyne (ABC) engages in an n→π* interaction with the C=O of α-azidoacetamides and forms a hydrogen bond with the N-H of α-diazoacetamides. These dipole-specific interactions act cooperatively with electronic activation of the strained π-bond to increase reactivity. We fou

SUBMITTER: Dones JM 

PROVIDER: S-EPMC11753763 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature