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Potassium Arylethynyltrifluoroborate as an Unstrained Dienophile for Ultrafast and On Demand Activation of Bioorthogonal IEDDA Reactions

submitted on 24.04.2019, 20:34 and posted on 25.04.2019, 19:53 by Zijian Guo, Bruno Oliveira, Claudio D. Navo, Pedro M. S. D. Cal, Francisco Corzana, Gonzalo Jiménez-Osés, Gonçalo Bernardes

Strained alkenes and alkynes are the predominant dienophiles used in inverse electron-demand Diels-Alder (IEDDA) reactions, however, their instability, cross-reactivity and accessibility are problematic. Unstrained dienophiles, although physiologically stable and synthetically accessible, react with tetrazines significantly slower relative to strained variants. Here we report the development of potassium arylethynyltrifluoroborates as unstrained dienophiles for ultrafast, chemically triggered IEDDA reactions. By varying the substituents on the tetrazine (e.g. pyridyl- to benzyl-substituents), cycloaddition rates can vary from nearly spontaneous (t1/2≈ 9 s) to no reaction with the unstrained alkyne-BF3 dienophile. The reported system was applied to protein modification and enabled mutually orthogonal labelling of two distinct proteins.


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University of Cambridge


United Kingdom

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Declaration of Conflict of Interest

The authors declare no competing financial interests.