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Published on: May 29, 2018
Orthogonal Inverse-Electron-Demand Cycloaddition Reactions Controlled by Frontier Molecular Orbital Interactions
Dennis Svatunek1,2, Konrad Chojnacki3, Titas Deb3
1Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, California 90095, United States.
Abstract:
Chemoselective pairs of bioorthogonal reactants enable the simultaneous labeling of several biomolecules. Here, we access orthogonal click reactions by exploiting differences in frontier molecular orbital interaction energies in transition states. We establish that five-membered cyclic dienes are inert to isonitriles but readily react with strained alkynes, while tetrazines with bulky substituents readily react with isonitriles. Strained alkynes show an opposite reactivity pattern. The approach was demonstrated by orthogonally labeling two proteins with different fluorophores.
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Conjugated systems containing an even number of π-electron pairs undergo a conrotatory ring closure. For example, thermal electrocyclization of (2E,4E)-2,4-hexadiene, a conjugated diene containing two π-electron pairs, gives trans-3,4-dimethylcyclobutene.