Diels—Alder Cycloaddition to Unsaturated Sugars

We analyze the mechanism of the topochemically controlled difunctionalization of C60 and anthracene, where an anthracene molecule is transferred from one C60 monoadduct to another one under exclusive formation of equal amounts of C60 and the difficult to make antipodal C60 bisadduct. Our herein disclosed dispersion corrected DFT studies show the anthracene transfer to take place in a synchronous retro Diels-Alder/Diels-Alder reaction: an anthracene molecule dissociates from one fullerene under formation of an intermediate, while already undergoing stabilizing interactions with both neighboring fullerenes, facilitating the reaction kinetically. In the intermediate, a planar anthracene molecule is sandwiched between two neighboring fullerenes and forms equally strong "double-decker" type pi-pi stacking interactions with both of these fullerenes. Analysis with the distorsion interaction model shows that the anthracene unit of the intermediate is almost planar with minimal distorsions. This analysis sheds light on the existence of noncovalent interactions engaging both faces of a planar polyunsaturated ring and two convex fullerene surfaces in an unprecedented 'inverted sandwich' structure. Hence, it sheds light on new strategies to design functional fullerene based materials.

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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.

Download Full-text

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.

Download Full-text