How cycloalkane fusion enhances the cycloaddition reactivity of dibenzocyclooctynes.

ABSTRACT: Dibenzoannulated cyclooctynes have emerged as valuable compounds for bioorthogonal reactions. They are commonly used in combination with azides in strain-promoted 1,3-dipolar cycloadditions. They are typically, however, unreactive towards 3,6-disubstituted tetrazines in inverse electron-demand Diels-Alder cycloadditions. Recently a dibenzoannulated bicyclo[6.1.0]nonyne derivative (DMBO) with a cyclopropane fused to the cyclooctyne core was described, which showed surprising reactivity towards tetrazines. To elucidate the unusual reactivity of DMBO, we performed density functional theory calculations and revealed that a tub-like structure in the transition state results in a much lower activation barrier than in the absence of cyclopropane fusion. The same transition state geometry is found

SUBMITTER: Svatunek D 

PROVIDER: S-EPMC10848739 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature