Clip to Click: Controlling Inverse Electron-Demand Diels-Alder Reactions with Macrocyclic Tetrazines

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Abstract

A universal strategy to control tetrazine reactivity in the inverse electron-demand Diels-Alder (IEDDA) reaction was developed as "Clip to Click". Incorporating a chemical bridge into 3,6-diphenyl-1,2,4,5-tetrazine (macrocyclic tetrazine) rendered it unreactive toward trans-cyclooctene. A computational study revealed that the unreactive property of macrocyclic tetrazines is mainly due to the high distortion energy of tetrazine. We demonstrated that the cleavage ("Clip") of the macrocyclic linker can activate the tetrazine moiety for the IEDDA reaction ("Click").

Original languageEnglish
Pages (from-to)3223-3226
Number of pages4
JournalOrganic letters
Volume24
Issue number17
DOIs
Publication statusPublished - 2022 May 6

ASJC Scopus subject areas

  • Biochemistry
  • Physical and Theoretical Chemistry
  • Organic Chemistry

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