Convenient Synthesis of Highly Functionalized Pyrazolines via Mild, Photoactivated 1,3-Dipolar Cycloaddition

Wang, Yizhong; Vera, Claudia I. Rivera; Lin, Qing

doi:10.1021/ol7017328

Cited by 158 publications

(138 citation statements)

References 21 publications

(10 reference statements)

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“…The substituent effect is clearly position-dependent with the para-position producing the most pronounced rate enhancement (compare 10, 12, 13; or 14, 15, 16). In particular, tetrazole 11 carrying the para-NH 2 group afforded the fastest rate with k 2 value of 0.79 M −1 s −1 , nearly 200-fold faster than tetrazole 1 we used previously.5b As expected, tetrazole 11 also showed the highest yield (~50% after 75 sec) with the water-quenching product (~10%)5a and the dimerization product (~15%) [10] as the major side products. We further calculated the HOMO energies of the nitrile imines (Table 1) [9] and plotted E HOMO vs. Log(rate) to gauge the electronic effect on the nitrile imine reactivity (Figure 1).…”

supporting

confidence: 50%

Fast Alkene Functionalization In Vivo by Photoclick Chemistry: HOMO Lifting of Nitrile Imine Dipoles

Wang

Song

et al. 2009

Angewandte Chemie

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Bioorthogonal chemistry has attracted intense interest recently because, combined with genetic encoding, it provides a powerful covalent strategy to probe biomolecular dynamics and function in living systems.[1] A number of bioorthogonal reactions have been successfully developed, including Cu I -catalyzed cycloaddition ('click chemistry'), [2] strain-promoted cycloaddition,[3] Staudinger ligation,[4] photoinduced cycloaddition ('photoclick chemistry'), [5] and tetrazine ligation. [6] In applying bioorthogonal reactions to study biomolecular dynamics, it is imperative that the reaction proceeds in a time frame shorter than the biomolecules' half-lives, which is especially important in case of short-lived proteins, such as the endogenous tumor suppressor protein p53 with a half-life of only 40 min. [7] We recently reported a photoinduced 1,3-dipolar cycloaddition reaction for selective functionalization of an unactivated alkene in Escherichia coli.[5b] While the reaction proceeded selectively, the cycloaddition rate was rather low (k 2 = 0.00202 ± 0.00007 M −1 s −1 ). To accelerate the concerted cycloaddition reactions, two strategies have been commonly employed in the literature: ring strain and fluorine effect,[3] both of which work by lowering the LUMO energies of the dipolarophiles. Because enzymes involved in the biosynthetic/metabolic pathways utilize unnatural substrates that are structurally close to the natural ones, it is typically easier to encode small groups such as allyl group into biomolecules than bulky ones. Therefore, it is more desirable if we can increase the reactivity of the nitrile imine dipoles in our photoclick chemistry. Since reaction rate is inversely related to free energy gap between dipole-HOMO and dipolarophile-LUMO for the type I HO-controlled 1,3-dipolar cycloaddition, [8] we envisioned that the cycloaddition reaction can be accelerated by lifting the dipole-HOMO energy. Herein, we report the identification of several simple, yet powerful tetrazole reagents for the photoclick chemistry by systematically tuning the HOMO energies of the nitrile imines, which afforded an extremely fast (< 1 min) labeling of an alkenecontaining protein in E. coli.

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confidence: 50%

Fast Alkene Functionalization In Vivo by Photoclick Chemistry: HOMO Lifting of Nitrile Imine Dipoles

Wang

Song

et al. 2009

Angewandte Chemie

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“…23 . Based on these observations, we also suggest that the tetrazine by-products previously reported during pyrazoline syntheses 15,16 may have been Wanzlick dimers, as their NMR profile would appear similar. Furthermore, we did not observe tetrazine by-products during our syntheses of pyrazoline adducts.…”

Section: Scheme 3 Trapping Of Nitrile Imine 13 By Isopropyl Alcoholsupporting

confidence: 70%

“…Previous accounts had reported the formation of tetrazine 10 from the dimerisation of the nitrile imine intermediate 6, in contrast to the triazoles isolated in the current study. 15 With a range of suitably functionalised tetrazole systems in hand, we conducted a solvent screen; a number of which were tolerated in the reaction, including: DCM, MeCN, TBME, 2-MeTHF, EtOAc, toluene and DMF. However, DMSO failed to produce any reaction due to inhibition of nitrile imine formation.…”

mentioning

confidence: 99%

Regiospecific Synthesis of N2-Aryl 1,2,3-Triazoles from 2,5-Disubstituted Tetrazoles via Photochemically Generated Nitrile Imine Intermediates

Stewart

Harris

Jamieson

2014

Synlett

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This version is available at https://strathprints.strath.ac.uk/51137/ Strathprints is designed to allow users to access the research output of the University of Strathclyde. Unless otherwise explicitly stated on the manuscript, Copyright © and Moral Rights for the papers on this site are retained by the individual authors and/or other copyright owners. Please check the manuscript for details of any other licences that may have been applied. You may not engage in further distribution of the material for any profitmaking activities or any commercial gain. You may freely distribute both the url (https://strathprints.strath.ac.uk/) and the content of this paper for research or private study, educational, or not-for-profit purposes without prior permission or charge.Any correspondence concerning this service should be sent to the Strathprints administrator: strathprints@strath.ac.ukThe Strathprints institutional repository (https://strathprints.strath.ac.uk) is a digital archive of University of Strathclyde research outputs. It has been developed to disseminate open access research outputs, expose data about those outputs, and enable the management and persistent access to Strathclyde's intellectual output. Abstract:The synthesis of N2-aryl 1,2,3-triazoles from 2,5-disubstituted tetrazoles was achieved under photochemical conditions. This simple and mild one step reaction provides regiospecific access to 2,4,5-substituted 1,2,3-triazoles via a nitrile imine intermediate. Syntheses of alkyl and heterocylic derivatives were also investigated.

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“…The resulting cycloadduct displays strong fluorescence in a specific wavelength ranges, depending on the substituents of the diaryl tetrazole species. 187 The reaction is irreversible and occurs without the need of a…”

Section: Figure 10mentioning

confidence: 99%

“…187 catalyst. Full conversion of the reagents, rapid and exclusive formation of the desired cycloadduct can be achieved.…”

Section: Scheme 13mentioning

confidence: 99%

From UV to NIR light, photo-triggered 1,3 dipolar cycloadditions as a modern ligation method in solution and on surface

Lederhose¹

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angefertigt.Ich erkläre hiermit, dass ich die vorliegende Arbeit im Rahmen der Betreuung durch Prof. tracking. In addition, the trigger wavelength of the pyrene functionalized tetrazole was extended deep into the NIR range via the combination of the NITEC with upconversion nanoparticles (UCNPs). Assisted by the UCNPs, photoinduced ligation of both, small and macromolecules was obtained with irradiation at 974 nm. Full conversion and rapid formation of the desired pyrazoline cycloadducts were observed. In addition, a block copolymer featuring the biological relevant biotin moiety was prepared via NITEC at 974 nm, demonstrating the suitability of the approach for applications in the field of biology. Biotin was found to retain bioactivity after being exposed to the NITEC reaction conditions. The efficient penetration ability of the NIR irradiation applied was verified by 'through tissue' conjugation experiments. After the NITEC reaction was demonstrated to be a powerful ligation tool in solution, the concept was employed for the modification of surfaces in a λ-orthogonal approach. The selective ability of the pyrene tetrazole and an UV-active diaryl tetrazole to undergo independent NITEC reactions at 410 -420 nm, and 320 nm respectively, was demonstrated in solution. Importantly, the UV-active tetrazole remains unreacted if exposed to visible light, even for prolonged irradiation times. Subsequently, a surface grafted with pyrene functional tetrazole and UV-active tetrazole was prepared and utilized for formation of advanced patterned surfaces.

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Convenient Synthesis of Highly Functionalized Pyrazolines via Mild, Photoactivated 1,3-Dipolar Cycloaddition

Cited by 158 publications

References 21 publications

Fast Alkene Functionalization In Vivo by Photoclick Chemistry: HOMO Lifting of Nitrile Imine Dipoles

Fast Alkene Functionalization In Vivo by Photoclick Chemistry: HOMO Lifting of Nitrile Imine Dipoles

Regiospecific Synthesis of N2-Aryl 1,2,3-Triazoles from 2,5-Disubstituted Tetrazoles via Photochemically Generated Nitrile Imine Intermediates

From UV to NIR light, photo-triggered 1,3 dipolar cycloadditions as a modern ligation method in solution and on surface

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