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Abstract Inverse electron demand Diels–Alder reactions betweens‐tetrazines and strained dienophiles have numerous applications in fluorescent labeling of biomolecules. Herein, we investigate the effect of the dienophile on the fluorescence enhancement obtained upon reaction with a tetrazine‐quenched fluorophore and study the possible mechanisms of fluorescence quenching by both the tetrazine and its reaction products. The dihydropyridazine obtained from reaction with a strained cyclooctene shows a residual fluorescence quenching effect, greater than that exerted by the pyridazine arising from reaction with the analogous alkyne. Linear and ultrabroadband two‐dimensional electronic spectroscopy experiments reveal that resonance energy transfer is the mechanism responsible for the fluorescence quenching effect of tetrazines, whereas a mechanism involving more intimate electronic coupling, likely photoinduced electron transfer, is responsible for the quenching effect of the dihydropyridazine. These studies uncover parameters that can be tuned to maximize fluorogenic efficiency in bioconjugation reactions and reveal that strained alkynes are better reaction partners for achieving maximum contrast ratio.
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Benzocyclobutadienes: An Unusual Mode of Access Reveals Unusual Modes of Reactivity
Abstract The reaction of an aryne with an alkyne to generate a benzocyclobutadiene (BCB) intermediate is rare. We report here examples of this reaction, revealed by Diels–Alder trapping of the BCB by either pendant or external electron‐deficient alkynes. Mechanistic delineation of the reaction course is supported by DFT calculations. A three‐component process joining the benzyne first with an electron‐rich and then with an electron‐poor alkyne was uncovered. Reactions in which the BCB functions in a rarely observed role as a 4π diene component in Diels–Alder reactions are reported. The results also shed new light on aspects of the hexadehydro‐Diels–Alder reaction used to generate the benzynes.
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- Award ID(s):
- 1665389
- PAR ID:
- 10063018
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Angewandte Chemie International Edition
- Volume:
- 57
- Issue:
- 31
- ISSN:
- 1433-7851
- Page Range / eLocation ID:
- p. 9901-9905
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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