Professor Alabugin's team has developped cycloalkynes with a twisted polyaromatic backbone to add axial chirality to the click chemistry toolbox. The “twisted and bent” cyclodecyne structural motif can be intertwined with dormant electronic effects to open a conceptually new way to control click reactivity. Although endocyclic heteroatoms can provide dual stabilization to the cycloalkyne via hyperconjugative (direct) and conjugative (remote) effects, these effects are weakened by the geometric constraints imposed by the twisted backbone. Structural reorganization in the transition state (TS) removes these constraints and unlocks the power of remote electronic effects for selective TS stabilization.
The chiral cyclodecynes can be prepared on gram scale in an enantiopure form and purified by recrystallization. Experimental kinetics confirm that these twisted cyclodecynes can be more reactive towards azides than activated cyclononynes and approach the reactivity of cyclooctynes.
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