Recyclable Polymeric π-Acid Catalyst Effective in Aqueous and Solvent-Free Inverse-Electron-Demand Aza-Diels-Alder Reactions

We report an air-stable bisboron complex as an efficient catalyst for the inverse electron-demand Diels–Alder (IEDDA) reaction of 1,2-diazine as well as 1,2,4,5-tetrazine. Its stability towards air and moisture was demonstrated by NMR studies enabling its application in organic transformations without glovebox. A one-pot procedure for its synthesis was developed starting from 1,2-bis(trimethylsilyl)benzene greatly enhancing its practicality. Comparative reactions were carried out to evaluate its catalytic activity in IEDDA reactions of diazine including phthalazine as well as 1,2,4,5-tetrazine.

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Influence of Reactant Polarity on the Course of the Inverse-Electron-Demand Diels−Alder Reaction. A DFT Study of Regio- and Stereoselectivity, Presence of Lewis Acid Catalyst, and Inclusion of Solvent Effects in the Reaction between Nitroethene and Substituted Ethenes

The Journal of Organic Chemistry ◽

10.1021/jo990331y ◽

1999 ◽

Vol 64 (16) ◽

pp. 5867-5875 ◽

Cited By ~ 90

Author(s):

Luis R. Domingo ◽

Manuel Arnó ◽

Juan Andrés

Keyword(s):

Lewis Acid ◽

Solvent Effects ◽

Acid Catalyst ◽

Alder Reaction ◽

Diels Alder ◽

Dft Study ◽

Inverse Electron Demand ◽

Diels Alder Reaction ◽

Lewis Acid Catalyst ◽

Electron Demand

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

10.26434/chemrxiv.8038685.v1 ◽

2019 ◽

Author(s):

Zijian Guo ◽

Bruno Oliveira ◽

Claudio D. Navo ◽

Pedro M. S. D. Cal ◽

Francisco Corzana ◽

...

Keyword(s):

Protein Modification ◽

Cross Reactivity ◽

Diels Alder ◽

Inverse Electron Demand ◽

On Demand ◽

Strained Alkenes ◽

Electron Demand

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

10.26434/chemrxiv.8038685 ◽

2019 ◽

Author(s):

Zijian Guo ◽

Bruno Oliveira ◽

Claudio D. Navo ◽

Pedro M. S. D. Cal ◽

Francisco Corzana ◽

...

Keyword(s):

Protein Modification ◽

Cross Reactivity ◽

Diels Alder ◽

Inverse Electron Demand ◽

On Demand ◽

Strained Alkenes ◽

Electron Demand

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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