Metal-Organic Frameworks (MOFs) and Covalent Organic Frameworks (COFs) are highly porous, crystalline materials designed for precise molecular interactions in areas such as gas storage, molecular separation, catalysis, and drug delivery. Their modular architectures enable fine control over pore size, surface area, and chemical environment, making them indispensable tools in contemporary materials science. The transformative impact of this class of materials was recognized with the 2025 Nobel Prize in Chemistry, awarded to Susumu Kitagawa, Richard Robson, and Omar Yaghi for their pioneering development of MOFs and their contribution to sustainable technologies.
The design and selection of linkers are central to the development of both functional MOFs and COFs, as they largely determine the resulting framework’s topology, porosity, and reactivity. Linkers can vary in several key parameters:
- Donor groups
- Connectivity (di-, tri-, tetra-, or multitopic)
- Size and linearity
- Symmetry
- Functionalization with additional organic substituents
We provide an extensive range of linkers for MOF and COF synthesis, readily available from stock.
- For MOFs: N-heterocyclic linkers, aldehyde linkers, amine linkers, carboxylic acids, hydroxy linkers, and monodentate nitrogen ligands.
- For COFs: Alkynyl linkers, amine linkers, boronic and borate linkers, nitrile linkers, and nitro linkers.
In addition to our comprehensive catalog, we also provide custom synthesis, ensuring solutions precisely aligned with your research objectives.
Examples of Enamine linkers for MOFs and COFs:
A well-known bioorthogonal reaction is the Inverse Electron Demand Diels–Alder (IEDDA) cycloaddition between 1,2,4,5-tetrazines (electron-deficient dienes) and strained alkenes (such as norbornenes, trans-cyclooctenes, and cyclopropenes). This reaction is exceptionally fast, does not require a catalyst, and proceeds cleanly in complex biological systems without perturbing the biological milieu. The two major applications of tetrazine-based cycloadditions include: bioconjugation and click-to-release chemistry
Another important application of tetrazines in chemical biology is their ability to quench fluorescence. When a tetrazine is attached to a fluorophore, it quenches the fluorescence; however, after the cycloaddition reaction, the fluorescence is restored.
Enamine offers a wide range of functionalized tetrazines, all available from stock.
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1-(1,2,4,5-tetrazin-3-yl)methanamine hydrochloride
CAS 2252340-10-4 (hydrochloride), 1414369-55-3 (base), Cat. No EN300-45381399
The simplest tetrazine derivative featuring a primary amine functionality.
- J. C. Sarris, T. Hansen, M. A. R. de Geus, E. Maurits, W. Doelman, H. S. Overkleeft, J. D. C. Codée, D. V. Filippov and S. I. van Kasteren, Chem. Eur. J., 2018, 24, 18075. DOI: 10.1002/chem.201803839
2-(6-methyl-1,2,4,5-tetrazin-3-yl)ethan-1-amine hydrochloride
CAS 2252340-03-5 (hydrochloride), 2171095-25-1 (base), Cat. No EN300-47338928
The compound is useful both as a pH-independent component in click-to-release chemistry and as a compact tetrazine bearing an amine group for ligation reactions.
- J. C. Sarris, T. Hansen, M. A. R. de Geus, E. Maurits, W. Doelman, H. S. Overkleeft, J. D. C. Codée, D. V. Filippov and S. I. van Kasteren, Chem. Eur. J., 2018, 24, 18075. DOI: 10.1002/chem.201803839
- Shi, J. Li, X. He, S. Zhou, H. Sun and H. Wu, Org. Lett., 2022, 24, 3368–3372. DOI: 10.1021/acs.orglett.2c01118
1-[4-(1,2,4,5-tetrazin-3-yl)phenyl]methanamine hydrochloride
CAS 1416711-59-5 (hydrochloride), 1092689-33-2 (base), Cat. No EN300-189526
A well-known tetrazine used in IEDDA ligations, featuring an amino moiety.
- Brudno, R. M. Desai, B. J. Kwee, N. S. Joshi, M. Aizenberg and D. J. Mooney, ChemMedChem, 2015, 10, 617–620. DOI: 10.1002/cmdc.201402527
- S. Erdmann, H. Takakura, A. D. Thompson, F. Rivera-Molina, E. S. Allgeyer, J. Bewersdorf, D. Toomre and A. Schepartz, Angew. Chem. Int. Ed., 2014, 53, 10242–10246. DOI: 10.1002/anie.201403349
- Uttamapinant, J. D. Howe, K. Lang, V. Beránek, L. Davis, M. Mahesh, N. P. Barry and J. W. Chin, J. Am. Chem. Soc., 2015, 137, 4602–4605. DOI: 10.1021/ja512838z
1-[4-(6-methyl-1,2,4,5-tetrazin-3-yl)phenyl]methanamine hydrochloride
CAS 1596117-29-1 (hydrochloride), 1345955-28-3 (base), Cat. No EN300-25385661
This well-known tetrazine, bearing an amine handle, is employed in both IEDDA ligations and click-to-release chemistry.
- Sen, D. Gahtory, J. Escorihuela, J. Firet, S. P. Pujari and H. Zuilhof, Chem. Eur. J., 2017, 23, 13015. DOI: 10.1002/chem.201703103
- Si, H. Zhu, J. Wang, Q. Zhang, Y. Li, X. Pan and J. Zhang, Bioorg. Chem., 2023, 135, 106497. DOI: 10.1016/j.bioorg.2023.106497
- A. J. C. Sarris, T. Hansen, M. A. R. de Geus, E. Maurits, W. Doelman, H. S. Overkleeft, J. D. C. Codée, D. V. Filippov and S. I. van Kasteren, Chem. Eur. J., 2018, 24, 18075. DOI: 10.1002/chem.201803839
1-{4-[6-(pyrimidin-2-yl)-1,2,4,5-tetrazin-3-yl]phenyl}methanamine hydrochloride
CAS 2252340-09-1 (hydrochloride), 1345955-30-7 (base), Cat. No EN300-47337814
This tetrazine exhibits enhanced reactivity in IEDDA reactions due to the electron-withdrawing effect of the pyrimidine ring. It is used in ligation reactions as well as a pH-independent partner in click-to-release methodology.
- J. C. Sarris, T. Hansen, M. A. R. de Geus, E. Maurits, W. Doelman, H. S. Overkleeft, J. D. C. Codée, D. V. Filippov and S. I. van Kasteren, Chem. Eur. J., 2018, 24, 18075. DOI: 10.1002/chem.201803839
- I. Willems, N. Li, B. I. Florea, M. Ruben, G. A. van der Marel and H. S. Overkleeft, Angew. Chem. Int. Ed., 2012, 51, 4431–4434. DOI: 10.1002/anie.201200923
4-(6-methyl-1,2,4,5-tetrazin-3-yl)benzoic acid
CAS 1345866-65-0, Cat. No EN300-25368796
A well-known, simple tetrazine with a carboxyl handle, used in both ligation reactions and click-to-release drug delivery.
- R. Edelmann, C. Bredack, S. Belli, P. Mohr, M.-P. Imhoff, F. Reggiani, E. A. Kusznir, A. C. Rufer, D. P. Holt, H. Valentine, D. F. Wong, R. F. Dannals, M. Honer and L. C. Gobbi, Bioconjugate Chem., 2023, 34, 1882–1893. DOI: 10.1021/acs.bioconjchem.3c00385
- Friederich, C. Xu, P. Raunft, H. L. S. Fuchs and M. Brönstrup, Chem. Commun., 2023, 59, 7451–7454. DOI: 10.1039/D3CC01334K
4-(6-methyl-1,2,4,5-tetrazin-3-yl)benzoic acid
CAS 1345866-66-1, Cat. No EN300-5505483
This well-known, simple tetrazine with a carboxyl handle is commonly used in bioorthogonal ligation reactions.
- Linden and O. Vázquez, Chem. Eur. J., 2020, 26, 10014. DOI: 10.1002/chem.202001718
- R. Edelmann, C. Bredack, S. Belli, P. Mohr, M.-P. Imhoff, F. Reggiani, E. A. Kusznir, A. C. Rufer, D. P. Holt, H. Valentine, D. F. Wong, R. F. Dannals, M. Honer and L. C. Gobbi, Bioconjugate Chem., 2023, 34, 1882–1893. DOI: 10.1021/acs.bioconjchem.3c00385
- E. Z. Klier, A. M. M. Gest, J. G. Martin, R. Roo, M. X. Navarro, L. Lesiak, P. E. Deal, N. Dadina, J. Tyson, A. Schepartz and E. W. Miller, J. Am. Chem. Soc., 2022, 144, 12138–12146. DOI: 10.1021/jacs.2c02664
2-[4-(1,2,4,5-tetrazin-3-yl)phenyl]acetic acid
CAS 1380500-92-4, Cat. No EN300-5503971
This carboxyl-containing tetrazine is widely used in bioorthogonal ligations, particularly in proteomics and antibody-drug conjugation.
- M. Zeglis, F. Emmetiere, N. Pillarsetty, R. Weissleder, J. S. Lewis and T. Reiner, ChemistryOpen, 2014, 3, 48–53. DOI: 10.1002/open.201402000
- Fang, S. Chakraborty, E. M. Dieter, Z. E. Potter, C. K. Lombard and D. J. Maly, J. Am. Chem. Soc., 2019, 141, 11912–11922. DOI: 10.1021/jacs.9b02963
- B. M. Poulie, E. Sporer, L. Hvass, J. T. Jørgensen, P. J. Kempen, S. I. Lopes van den Broek, V. Shalgunov, A. Kjaer, A. I. Jensen and M. M. Herth, Chem. Eur. J., 2022, 28, e202201847. DOI: 10.1002/chem.202201847
2-[4-(6-methyl-1,2,4,5-tetrazin-3-yl)phenyl]acetic acid
CAS 1380500-88-8, Cat. No EN300-233665
This carboxyl-containing tetrazine is employed in prodrug activation and proteomics applications.
- J. M. Song, A. Menon, D. C. Mitchell, O. T. Johnson and A. L. Garner, ACS Comb. Sci., 2017, 19, 763–769. DOI: 10.1021/acscombsci.7b00128
- M. M. A. Mitry, M. L. Dallas, S. Y. Boateng, F. Greco and H. M. I. Osborn, Bioorg. Chem., 2024, 147, 107304. DOI: 10.1016/j.bioorg.2024.107304
- Y. Ma, Y. Zhou, J. Long, Q. Sun, Z. Luo, W. Wang, T. Hou, L. Yin, L. Zhao, J. Peng and Y. Ding, Angew. Chem. Int. Ed., 2024, 63, e202318372. DOI: 10.1002/anie.202318372
2,5-dioxopyrrolidin-1-yl 2-[4-(6-methyl-1,2,4,5-tetrazin-3-yl)phenyl]acetate
CAS 1644644-96-1, Cat. No EN300-7406911
A ready-to-use tetrazine containing an acylation reagent, used in prodrug activation and proteomics.
- M. Song, A. Menon, D. C. Mitchell, O. T. Johnson and A. L. Garner, ACS Comb. Sci., 2017, 19, 763–769. DOI: 10.1021/acscombsci.7b00128
- M. A. Mitry, M. L. Dallas, S. Y. Boateng, F. Greco and H. M. I. Osborn, Bioorg. Chem., 2024, 147, 107304. DOI: 10.1016/j.bioorg.2024.107304
- Y. Ma, Y. Zhou, J. Long, Q. Sun, Z. Luo, W. Wang, T. Hou, L. Yin, L. Zhao, J. Peng and Y. Ding, Angew. Chem. Int. Ed., 2024, 63, e202318372. DOI: 10.1002/anie.202318372
3,6-dimethyl 1,2,4,5-tetrazine-3,6-dicarboxylate
CAS 2166-14-5, Cat. No EN300-211397
A highly reactive tetrazine in IEDDA chemistry. Although not suitable for bioorthogonal transformations due to its high reactivity, the compound possesses immense synthetic potential as a building block in [4+2] cycloadditions.
- H. Marzabadi, S. P. Kelty and A. Altamura, Carbohydr. Res., 2022, 519, 108623. DOI: 10.1016/j.carres.2022.108623
- D. Helm, J. E. Moore, A. Plant and J. P. A. Harrity, Angew. Chem. Int. Ed., 2005, 44, 3889–3892. DOI: 10.1002/anie.200500288
- Sauer, P. Bäuerlein, W. Ebenbeck, C. Gousetis, H. Sichert, T. Troll, F. Utz and U. Wallfahrer, Eur. J. Org. Chem., 2001, 2001, 2629–2638. DOI: 10.1002/1099-0690(200107)2001:14<2629::AID-EJOC2629>3.0.CO;2-2
3-bromo-1,2,4,5-tetrazine
CAS 2396594-00-4, Cat. No EN300-27145343
A versatile small building block for the incorporation of a tetrazine fragment via arylation and cross-coupling reactions. 3-Bromotetrazine readily arylates O- and N-nucleophiles and also reacts with a variety of boronic acids under Suzuki–Miyaura coupling conditions. The products of these reactions include tetrazine-containing amino acids, fluorogenic probes, and compounds for click-to-release bioorthogonal transformations.
- D. Schnell, L. V. Hoff, A. Panchagnula, M. H. H. Wurzenberger, T. M. Klapötke, S. Sieber, A. Linden and K. Gademann, Chem. Sci., 2020, 11, 3042–3047. DOI: 10.1039/C9SC06169J
- Ros, M. Bellido, X. Verdaguer, L. Ribas de Pouplana and A. Riera, Bioconjugate Chem., 2020, 31, 933–938. DOI: 10.1021/acs.bioconjchem.0c00052
- V. Hoff, S. D. Schnell, A. Tomio, A. Linden and K. Gademann, Org. Lett., 2021, 23, 5689–5692. DOI: 10.1021/acs.orglett.1c01813
3‑bromo‑6‑methyl‑1,2,4,5‑tetrazine
CAS 67131‑33‑3, Cat. No EN300‑7499546
A small building block for the incorporation of a tetrazine fragment via cross‑coupling reactions, including Suzuki, Sonogashira, and Stille couplings. The resulting products include tetrazine‑containing amino acids and fluorogenic tetrazine probes.
- V. Hoff, S. D. Schnell, A. Tomio, A. Linden and K. Gademann, Org. Lett., 2021, 23, 5689–5692. DOI: 10.1021/acs.orglett.1c01813
- Ros, A. Prades, D. Forson, J. Smyth, X. Verdaguer, L. Ribas de Pouplana and A. Riera, Chem. Commun., 2020, 56, 11086–11089. DOI: 10.1039/D0CC03482G
- Kim, H. Son and S. B. Park, Angew. Chem. Int. Ed., 2023, 62, e202310665. DOI: 10.1002/anie.202310665
3-bromo-6-phenyl-1,2,4,5-tetrazine
CAS 35011‑53‑1, Cat. No EN300‑34651
The compound can serve as a precursor to various 3-substituted tetrazines via cross-coupling reactions. It has also been employed in the construction of fluorescent amino acid derivatives.
- Ros, M. Bellido, J. A. Matarin, A. Gallen, M. Martínez, L. Rodríguez, X. Verdaguer, L. Ribas de Pouplana and A. Riera, RSC Adv., 2022, 12, 14321–14327. DOI: 10.1039/D2RA02531K
- Ros, A. Prades, D. Forson, J. Smyth, X. Verdaguer, L. Ribas de Pouplana and A. Riera, Chem. Commun., 2020, 56, 11086–11089. DOI: 10.1039/D0CC03482G
3-(4-iodophenyl)-6-methyl-1,2,4,5-tetrazine
CAS 56108‑04‑4, Cat. No EN300‑1692436
The compound is used in the construction of fluorescent probes via Pd-catalyzed cross-coupling reactions, including Sonogashira and Stille couplings.
- Wieczorek, T. Buckup and R. Wombacher, Org. Biomol. Chem., 2014, 12, 4177–4185. DOI: 10.1039/C4OB00245H
- Lee, W. Cho, J. Sung, E. Kim and S. B. Park, J. Am. Chem. Soc., 2018, 140, 974–983. DOI: 10.1021/jacs.7b10433
dichloro-1,2,4,5-tetrazine
CAS 106131‑61‑7, Cat. No EN300‑1726354
Dichlorotetrazine is a versatile arylation agent, with both chlorine atoms capable of undergoing successive substitution. This property enables the construction of a wide range of disubstituted tetrazine-containing compounds. Cross-coupling reactions are possible under Suzuki–Miyaura conditions. Additionally, dichlorotetrazine is a well-established building block in organic synthesis and materials science.
- Canovas, M. Moreau, C. Bernhard, A. Oudot, M. Guillemin, F. Denat and V. Goncalves, Angew. Chem. Int. Ed., 2018, 57, 10646. DOI: 10.1002/anie.201806053
- M. Bender, T. C. Chopko, T. M. Bridges and C. W. Lindsley, Org. Lett., 2017, 19, 5693–5696. DOI: 10.1021/acs.orglett.7b02868
- Santos, D. S. Rivero, Y. Pérez-Pérez, E. Martín-Encinas, J. Pasán, A. H. Daranas and R. Carrillo, Angew. Chem. Int. Ed., 2021, 60, 18783. DOI: 10.1002/anie.202106230
3-methyl-6-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1,2,4,5-tetrazine
CAS 1939022‑20‑4, Cat. No EN300‑45587846
This boronic acid ester has been successfully used for the construction of tetrazine-based fluorogenic probes via Suzuki–Miyaura coupling. The resulting probes exhibit low-wavelength excitability and a high fluorescence quantum yield. IEDDA methodology has been employed for probe activation through tetrazine-to-pyridazine conversion.
- Kozma, G. Estrada Girona, G. Paci, E. A. Lemke and P. Kele, Chem. Commun., 2017, 53, 6696–6699. DOI: 10.1039/C7CC02212C
- Teng, R. Zhang, B. Yang, H. Yang, X. Li, D. Yin, X. Feng and Y. Tian, J. Mater. Chem. B, 2022, 10, 8642–8649. DOI: 10.1039/D2TB01893D
- Knorr, E. Kozma, A. Herner, E. A. Lemke and P. Kele, Chem. Eur. J., 2016, 22, 8972. DOI: 10.1002/chem.201600590
3-chloro-6-methoxy-1,2,4,5-tetrazine
CAS 614756‑34‑2, Cat. No EN300‑7627635
This compound is used in the construction of tetrazine-based fluorogenic probes.
- Audebert, F. Miomandre, G. Clavier, M.-C. Vernières, S. Badré and R. Méallet-Renault, Chem. Eur. J., 2005, 11, 5667–5673. DOI: 10.1002/chem.200401252
- Wu and D. F. O’Shea, Chem. Commun., 2017, 53, 10804–10807. DOI: 10.1039/C7CC06545K
2-(6-methyl-1,2,4,5-tetrazin-3-yl)ethan-1-ol
CAS 1225146‑57‑5, Cat. No EN300‑7500987
A small and simple tetrazine bearing a hydroxyl moiety. The compound can be used in IEDDA ligation and also finds application in the synthesis of alkenyl tetrazines, which are employed as fluorogenic probes.
- V. Mayer, A. Murnauer, M.-K. von Wrisberg, M.-L. Jokisch and K. Lang, Angew. Chem. Int. Ed., 2019, 58, 15876. DOI: 10.1002/anie.201908209
- Wu, J. Yang, J. Šečkutė and N. K. Devaraj, Angew. Chem. Int. Ed., 2014, 53, 5805–5809. DOI: 10.1002/anie.201400135
[4-(6-methyl-1,2,4,5-tetrazin-3-yl)phenyl]methanol
CAS 1380500‑87‑7, Cat. No EN300‑7499596
This alcohol has been used in the construction of a bioorthogonal theranostic scaffold that enables click-to-release prodrug delivery accompanied by fluorescence emission.
- Pang, S. Feng, B. Huang, J. Zhou, L. Zhan and Y.-Q. Long, J. Med. Chem., 2025, 68, 3824–3836. DOI: 10.1021/acs.jmedchem.4c02965
[3-(6-methyl-1,2,4,5-tetrazin-3-yl)phenyl]methanol
CAS 2382712‑97‑0, Cat. No EN300‑45587416
This alcohol has been used in the synthesis of tetrazine-containing amino acids.
- S. V. Mayer, A. Murnauer, M.-K. von Wrisberg, M.-L. Jokisch and K. Lang, Angew. Chem. Int. Ed., 2019, 58, 15876. DOI: 10.1002/anie.201908209
4-(6-methyl-1,2,4,5-tetrazin-3-yl)phenol
CAS 58884‑35‑8, Cat. No EN300‑2698863
A simple tetrazine bearing a phenolic moiety. It exhibits modest reactivity in the IEDDA reaction.
- M. R. Edelmann, C. Bredack, S. Belli, P. Mohr, M.-P. Imhoff, F. Reggiani, E. A. Kusznir, A. C. Rufer, D. P. Holt, H. Valentine, D. F. Wong, R. F. Dannals, M. Honer and L. C. Gobbi, Bioconjugate Chem., 2023, 34, 1882–1893. DOI: 10.1021/acs.bioconjchem.3c00385
3-[4-(bromomethyl)phenyl]-6-methyl-1,2,4,5-tetrazine
CAS 3017266‑45‑1, Cat. No EN300‑46767537
A tetrazine-containing alkylating agent. This compound has been used in the construction of DOTA-based lanthanide complexes, which can be utilized with peptide-based delivery systems to penetrate the blood–brain barrier.
- Woolley, Y. Wu, L. Xiong, H.-F. Chau, J. Zhang, G.-L. Law, K.-L. Wong and N. J. Long, Chem. Sci., 2025, 16, 3588–3597. DOI: 10.1039/D4SC02335H
3-[3-(bromomethyl)phenyl]-6-methyl-1,2,4,5-tetrazine
CAS 3017193‑98‑2, Cat. No EN300‑46614924
A tetrazine-containing alkylating agent.
- J. Zhao, H. Guo, Z. Wu and J.-H. Jiang, Chem. Commun., 2022, 58, 13393–13396. DOI: 10.1039/D2CC05628C
- J. Zhao, Z. Wu and J.-H. Jiang, in Live-Cell RNA Imaging, ed. S. Si, Methods in Molecular Biology, vol. 2875, Springer, New York, NY, 2025, pp. 165–175. DOI: 10.1007/978-1-0716-4248-1_14
3-(bromomethyl)-6-tert-butyl-1,2,4,5-tetrazine
CAS 2678593‑04‑7, Cat. No EN300‑37098638
This is an unusual tetrazine that displays low reactivity in IEDDA reactions due to the steric hindrance of the bulky tert-butyl substituent. Nevertheless, it has two notable applications:
- Bioorthogonal activation of fluorophores via an isonitrile–tetrazine click-to-release reaction.
- Use as a bioorthogonally removable protecting group, cleavable by isonitriles.
- Zhang, H. Xu, J. Li, D. Su, W. Mao, G. Shen, L. Li and H. Wu, Chem. Commun., 2022, 58, 573. DOI: 10.1039/D1CC05774J
- Tu, D. Svatunek, S. Parvez, H. J. Eckvahl, M. Xu, R. T. Peterson, K. N. Houk and R. M. Franzini, Chem. Sci., 2020, 11, 169–179. DOI: 10.1039/C9SC04649F
4-(6-methyl-1,2,4,5-tetrazin-3-yl)benzaldehyde
CAS 2196202‑78‑3, Cat. No EN300‑7499591
This tetrazine, bearing an aldehyde functionality, has been used in the construction of fluorogenic probes. Its mechanism relies on fluorescence quenching by the tetrazine moiety in the initial probe. Upon undergoing an IEDDA reaction, the tetrazine is converted to a pyridazine or dihydropyridazine, resulting in the loss of its quenching ability and restoration of the probe’s fluorescence.
- Wieczorek, P. Werther, J. Euchner and R. Wombacher, Chem. Sci., 2017, 8, 1506–1510. DOI: 10.1002/ejoc.201301375
- Werther, J. S. Möhler and R. Wombacher, Chem. Eur. J., 2017, 23, 18216. DOI: 10.1002/chem.201703607
3-(6-methyl-1,2,4,5-tetrazin-3-yl)benzaldehyde
CAS 2382712‑95‑8, Cat. No EN300‑7499590
This aldehyde-functionalized tetrazine has been used in the development of fluorogenic probes and bioorthogonally activatable photoredox catalysts. The mechanism relies on the intrinsic fluorescence quenching ability of the tetrazine moiety in the initial probe or catalyst. Upon undergoing an IEDDA reaction, the tetrazine is converted into a pyridazine or dihydropyridazine, which no longer exhibits quenching properties. This transformation restores the photochemical activity of the molecule.
- Linden, L. Zhang, F. Pieck, U. Linne, D. Kosenkov, R. Tonner and O. Vázquez, Angew. Chem. Int. Ed., 2019, 58, 12868. DOI: 10.1002/anie.201907093
- Kim, Y. Xu, J. H. Lim, J. Y. Lee, M. Li, J. M. Fox, M. Vendrell and J. S. Kim, J. Am. Chem. Soc., 2025, 147, 701–712. DOI: 10.1021/jacs.4c13131
- Wieczorek, P. Werther, J. Euchner and R. Wombacher, Chem. Sci., 2017, 8, 1506–1510. DOI: 10.1039/C6SC03879D
dimethyl-1,2,4,5-tetrazine
CAS 1558-23-2, Cat. No EN300-7316309
This small tetrazine serves two primary purposes: as a model substrate for the inverse electron-demand Diels–Alder (IEDDA) reaction, and as a trigger for click-to-release mechanisms from trans-cyclooctenes.
- M. Versteegen, R. Rossin, W. ten Hoeve, H. M. Janssen and M. S. Robillard, Angew. Chem. Int. Ed., 2013, 52, 14112–14116. DOI: 10.1002/anie.201305969
- C. T. Carlson, H. Mikula and R. Weissleder, J. Am. Chem. Soc., 2018, 140, 3603–3612. DOI: 10.1021/jacs.7b11217
- M. Versteegen, W. ten Hoeve, R. Rossin, M. A. R. de Geus, H. M. Janssen and M. S. Robillard, Angew. Chem. Int. Ed., 2018, 57, 10494. DOI: 10.1002/anie.201800402
3-phenyl-1,2,4,5-tetrazine
CAS 36022-11-4, Cat. No EN300-179268
A simple phenyl-substituted tetrazine is commonly used as a model substrate for mechanistic studies and for evaluating the reactivity of IEDDA-compatible dienophiles. Additionally, it serves as a valuable building block for the synthesis of pyridazines.
- Svatunek, M. Wilkovitsch, L. Hartmann, K. N. Houk and H. Mikula, J. Am. Chem. Soc., 2022, 144, 8171–8177. DOI: 10.1021/jacs.2c01056
- Eising, A. H. J. Engwerda, X. Riedijk, F. M. Bickelhaupt and K. M. Bonger, Bioconjugate Chem., 2018, 29, 3054–3059. DOI: 10.1021/acs.bioconjchem.8b00439
3-methyl-6-phenyl-1,2,4,5-tetrazine
CAS 38634-12-7, Cat. No EN300-25692525
This simple phenyl-substituted tetrazine is widely used as a model substrate for mechanistic investigations and for evaluating the reactivity of IEDDA-compatible dienophiles. It also serves as a valuable building block for the synthesis of pyridazines.
- Svatunek, M. Wilkovitsch, L. Hartmann, K. N. Houk and H. Mikula, J. Am. Chem. Soc., 2022, 144, 8171–8177. DOI: 10.1021/jacs.2c01056
- Svatunek, Top. Curr. Chem. (Z), 2024, 382, 17. DOI: 10.1007/s41061-024-00461-0
diphenyl-1,2,4,5-tetrazine
CAS 6830-78-0, Cat. No EN300-7400818
A simple diphenyl-tetrazine is commonly employed as a model substrate for mechanistic investigations and for assessing the reactivity of IEDDA-compatible dienophiles. It also serves as a valuable building block for the synthesis of pyridazines.
- Wei, K. Fu, Z. Yu, Z. Zhan, D. Chang and L. Shi, J. Am. Chem. Soc., 2025, 147, 14299–14307. DOI: 10.1021/jacs.4c18057
- Svatunek, Top. Curr. Chem. (Z), 2024, 382, 17. DOI: 10.1007/s41061-024-00461-0
bis(pyridin-2-yl)-1,2,4,5-tetrazine
CAS 1671-87-0, Cat. No EN300-1485623
Dipyridyl-substituted tetrazine is a well-known, highly reactive substrate in the inverse electron-demand Diels–Alder (IEDDA) reaction. It exhibits a broad range of applications, including click-to-release chemistry, coordination-assisted cycloadditions with vinyl boronic acids, mechanistic studies, and use as both a model substrate and a dienophile acceptor in organic synthesis.
- M. Versteegen, R. Rossin, W. ten Hoeve, H. M. Janssen and M. S. Robillard, Angew. Chem., Int. Ed., 2013, 52, 14112–14116. DOI: 10.1002/anie.201305969
- Eising, A. H. J. Engwerda, X. Riedijk, F. M. Bickelhaupt and K. M. Bonger, Bioconjugate Chem., 2018, 29, 3054–3059. DOI: 10.1021/acs.bioconjchem.8b00439
- Eising, B.-T. Xin, F. Kleinpenning, J. J. A. Heming, B. I. Florea, H. S. Overkleeft and K. M. Bonger, ChemBioChem, 2018, 19, 1648. DOI: 10.1002/cbic.201800275
diethyl [(6-methyl-1,2,4,5-tetrazin-3-yl)methyl]phosphonate
CAS 2067322-26-1, Cat. No EN300-52272694
A tetrazine bearing a phosphonate moiety is a valuable precursor for the preparation of fluorogenic probes. A biocompatible Horner–Wadsworth–Emmons (HWE) reaction involving tetrazine-based phosphonates has been developed to enable efficient and selective functionalization under mild conditions.
- Wang, H. Yang, J. Li, Q. Kong, S. Zhou, H. Sun, L. Pan, Q. Gong, P. Feng and H. Wu, Chin. Chem. Lett., 2024, 35, 109226. DOI: 10.1016/j.cclet.2023.109226
- Mao, J. Tang, L. Dai, X. He, J. Li, L. Cai, P. Liao, R. Jiang, J. Zhou and H. Wu, Angew. Chem., Int. Ed., 2021, 60, 2393. DOI: 10.1002/anie.202011544
Among the most well-known bioorthogonal transformations is the Strain-Promoted Azide–Alkyne Cycloaddition (SPAAC).
One component of the reaction, alkyl azide, is a common class of compounds that are commercially available or can be synthesized through simple chemical transformations. On the other hand, alkynes need to be strained to react at physiological temperatures without the use of a catalyst. Cyclooctynes and hetero-cycloalkynes are the smallest cyclic alkynes stable enough for practical applications. Yet, their inherent ring strain is what really sets them apart, enabling [3+2] cycloadditions with azides and other dipoles (like nitrile oxides, nitrile imines, and nitrones) without the need for catalysis, even at biological temperatures.1
Enamine offers a diverse selection of cyclooctynes, all readily available from stock, to support your research.
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We also provide custom synthesis of cyclooctynes, designed to meet your specific needs.
Below are some of the most relevant cyclootyne-based building blocks for your research. Each is available from stock.
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Biomedical applications of copper-free click chemistry: in vitro, in vivo, and ex vivo.
Kim E. and Koo H. Chem. Sci. 2019, 10, 7835. DOI: 10.1039/C9SC03368H
cyclooct-2-yn-1-ol
CAS 29916-92-5, Cat. No EN300-7551522
The simplest and smallest 1st-generation cyclooctyne derivative.
- T. Hagendorn and S. Bräse, Eur. J. Org. Chem., 2014, 1280. DOI: 10.1002/ejoc.201301375
- D. Kang and J. Kim, J. Am. Chem. Soc., 2021, 143, 5616. DOI: 10.1021/jacs.1c00885
2-(cyclooct-2-yn-1-yloxy)acetic acid
CAS 917756-42-4, Cat. No EN300-179238
This compound is one of the first cyclooctynes used for bioorthogonal ligation with azides. It has a small size and a simple structure. These features make it versatile for various bioorthogonal transformations.
- H. L. Evans, R. L. Slade, L. Carroll, G. Smith, Q.-D. Nguyen, L. Iddon, N. Kamaly, H. Stöckmann, F. J. Leeper, E. O. Aboagye and A. C. Spivey, Chem. Commun., 2012, 48, 991. DOI: 10.1039/C1CC16220A
- M. Burk, S. Rothstein and P. Dubé, Org. Process Res. Dev., 2018, 22, 108. DOI: 10.1021/acs.oprd.7b00275
- N. J. Agard, J. M. Baskin, J. A. Prescher, A. Lo and C. R. Bertozzi, ACS Chem. Biol., 2006, 1, 644. DOI: 10.1021/cb6003228
2,5-dioxopyrrolidin-1-yl 2-(cyclooct-2-yn-1-yloxy)acetate
CAS 1425803-45-7, Cat. No EN300-19594192
This compound is an activated ester of cyclooctynyloxyacetic acid, EN300-179238. It can be used directly for the acylation of amines or alcohols, facilitating the construction of molecules of interest for bioorthogonal ligation.
- C.-H. Lai, T.-C. Chang, Y.-J. Chuang, D.-L. Tzou and C.-C. Lin, Bioconjugate Chem., 2013, 24, 1698. DOI: 10.1021/bc400219t
- M. Burk, S. Rothstein and P. Dubé, Org. Process Res. Dev., 2018, 22, 108. DOI: 10.1021/acs.oprd.7b00275
- T. Wang, J. G. Vineberg, T. Honda and I. Ojima, Bioorg. Chem., 2018, 76, 458. DOI: 10.1016/j.bioorg.2017.12.018
2-(cyclooct-2-yn-1-yloxy)ethan-1-ol
CAS 1309581-54-1, Cat. No EN300-5256850
A small 1st-generation cyclooctyne with an alcohol moiety.
- T. Plass, S. Milles, C. Koehler, C. Schultz and E. A. Lemke, Angew. Chem., Int. Ed., 2011, 50, 3878. DOI: 10.1002/anie.201008178
- D. Guan, Y. Kurra, W. Liu and Z. Chen, Chem. Commun., 2015, 51, 2522. DOI: 10.1039/C4CC09179E
BCN-OH
CAS 1379662-52-8, Cat. No EN300-178372
Synonyms: [bicyclo[6.1.0]non-4-yn-9-yl]methanol
BCN-OH is the most famous cyclooctyne, known for its balance between high reactivity and small size.
The first and most studied transformation involving BCN-OH is the Strain-Promoted Azide–Alkyne Cycloaddition (SPAAC).
Nevertheless, it also finds application in cycloadditions with tetrazines and nitrile imines.
- D. Kim, H. Son and S. B. Park, Angew. Chem., Int. Ed., 2023, 62, e202310665. DOI: 10.1002/anie.202310665
- M. Fang, G. S. Kumar, S. Racioppi, H. Zhang, J. D. Rabb, E. Zurek and Q. Lin, J. Am. Chem. Soc., 2023, 145, 9959. DOI: 10.1021/jacs.2c12325
- G. S. Kumar, S. Racioppi, E. Zurek and Q. Lin, J. Am. Chem. Soc., 2022, 144, 57. DOI: 10.1021/jacs.1c10354
endo-BCN-OH
CAS 1263166-90-0, Cat. No EN300-342715
Synonyms: [(1R,8S,9S)-bicyclo[6.1.0]non-4-yn-9-yl]methanol; BCN-OH; (1α,8α,9β)-Bicyclo[6.1.0]non-4-yne-9-methanol; endo-Bicyclo[6.1.0]non-4-yn-9-ylmethanol; (1R,8S,9s)-Bicyclo[6.1.0]non-4-yn-9-ylmethanol
BCN-OH is the most famous cyclooctyne, known for its balance between high reactivity and small size. The first and most studied transformation involving BCN-OH is the Strain-Promoted Azide–Alkyne Cycloaddition (SPAAC). It also finds application in cycloadditions with tetrazines and nitrile imines. Endo-BCN-OH is the most reactive isomer in SPAAC.
- J. Dommerholt, S. Schmidt, R. Temming, L. J. A. Hendriks, F. P. J. T. Rutjes, J. C. M. van Hest, D. J. Lefeber, P. Friedl and F. L. van Delft, Angew. Chem., Int. Ed., 2010, 49, 9422. DOI: 10.1002/anie.201003761
- M. F. Debets, S. S. van Berkel, J. Dommerholt, A. J. Dirks, F. P. J. T. Rutjes and F. L. van Delft, Acc. Chem. Res., 2011, 44, 805. DOI: 10.1021/ar200059z
- M. Baalmann, L. Neises, S. Bitsch, H. Schneider, L. Deweid, P. Werther, N. Ilkenhans, M. Wolfring, M. J. Ziegler, J. Wilhelm, H. Kolmar and R. Wombacher, Angew. Chem., Int. Ed., 2020, 59, 12885. DOI: 10.1002/anie.201915079
exo-BCN-OH
CAS 1263291-41-3, Cat. No EN300-378398
Synonyms: [(1R,8S,9R)-bicyclo[6.1.0]non-4-yn-9-yl]methanol; (1α,8α,9α)-Bicyclo[6.1.0]non-4-yne-9-methanol; exo-Bicyclo[6.1.0]non-4-yn-9-ylmethanol
BCN-OH is the most famous cyclooctyne, known for its balance between high reactivity and small size. The first and most studied transformation involving BCN-OH is the Strain-Promoted Azide–Alkyne Cycloaddition (SPAAC). It also finds application in cycloadditions with tetrazines and nitrile imines.
- J. Dommerholt, S. Schmidt, R. Temming, L. J. A. Hendriks, F. P. J. T. Rutjes, J. C. M. van Hest, D. J. Lefeber, P. Friedl and F. L. van Delft, Angew. Chem., Int. Ed., 2010, 49, 9422. DOI: 10.1002/anie.201003761
- X. Li, Z. Liu and S. Dong, RSC Adv., 2017, 7, 44470. DOI: 10.1039/C7RA08136G
- K. Lang, L. Davis, S. Wallace, M. Mahesh, D. J. Cox, M. L. Blackman, J. M. Fox and J. W. Chin, J. Am. Chem. Soc., 2012, 134, 10317. DOI: 10.1021/ja302832g
endo-BCN-NHS carbonate
CAS 1426827-79-3, Cat. No EN300-18974406
Synonyms: BCN-NHS; [(1R,8S,9S)-bicyclo[6.1.0]non-4-yn-9-yl]methyl 2,5-dioxopyrrolidin-1-yl carbonate; (1α,8α,9β)-Bicyclo[6.1.0]non-4-yn-9-ylmethyl 2,5-dioxo-1-pyrrolidinyl carbonate; rel-(1R,8S,9s)-Bicyclo[6.1.0]non-4-yn-9-ylmethyl (2,5-dioxopyrrolidin-1-yl) carbonate
Endo-BCN-NHS carbonate is a ready-to-use derivative of the well-known cyclooctyne, BCN-OH, EN300-342715, which is recognized for its balance of high reactivity and compact size.
The primary and most extensively studied reaction involving BCN derivatives is the Strain-Promoted Azide–Alkyne Cycloaddition (SPAAC).
Endo-BCN derivatives are more reactive isomers in SPAAC, comparable to exo-BCN. They are also utilized in cycloadditions with tetrazines, tetrazoles and nitrile imines.
- A. Borrmann, S. Milles, T. Plass, J. Dommerholt, J. M. M. Verkade, M. Wießler, C. Schultz, J. C. M. van Hest, F. L. van Delft and E. A. Lemke, ChemBioChem, 2012, 13, 2094. DOI: 10.1002/cbic.201200407
- T. Komatsu, E. Kyo, H. Ishii, K. Tsuchikama, A. Yamaguchi, T. Ueno, K. Hanaoka and Y. Urano, J. Am. Chem. Soc., 2014, 142, 15644. DOI: 10.1021/jacs.0c05331
- G. S. Kumar, S. Racioppi, E. Zurek and Q. Lin, J. Am. Chem. Soc., 2022, 144, 57. DOI: 10.1021/jacs.1c10354
exo-BCN-NHS carbonate
CAS 1493802-77-9, Cat. No EN300-28319443
Synonyms: [(1R,8S,9R)-bicyclo[6.1.0]non-4-yn-9-yl]methyl 2,5-dioxopyrrolidin-1-yl carbonate; BCN-NHS; rel-((1R,8S,9r)-Bicyclo[6.1.0]non-4-yn-9-yl)methyl (2,5-dioxopyrrolidin-1-yl) carbonate
Exo-BCN-NHS carbonate is a ready-to-use derivative of the well-known cyclooctyne, BCN-OH, EN300-378398, which is recognized for its balance of high reactivity and compact size.
The primary and most extensively studied reaction involving BCN derivatives is the Strain-Promoted Azide–Alkyne Cycloaddition (SPAAC).
They are also utilized in cycloadditions with tetrazines and nitrile imines.
- K. Lang, L. Davis, S. Wallace, M. Mahesh, D. J. Cox, M. L. Blackman, J. M. Fox and J. W. Chin, J. Am. Chem. Soc., 2012, 134, 10317. DOI: 10.1021/ja302832g
- X. Chen, F. Li and Y.-W. Wu, Chem. Commun., 2015, 51, 16537. DOI: 10.1039/C5CC05208D
endo-BCN-carbaldehyde
CAS 1426827-91-9, Cat. No EN300-46452871
Synonyms: (1R,8S,9S)-bicyclo[6.1.0]non-4-yne-9-carbaldehyde
Bicyclononyne with a carbonyl functionality is a derivative of the well-known cyclooctyne BCN-OH, EN300-342715. Endo-izomer.
- E. H. P. Leunissen, M. H. L. Meuleners, J. M. M. Verkade, J. Dommerholt, J. G. J. Hoenderop and F. L. van Delft, ChemBioChem, 2014, 15, 1446. DOI: 10.1002/cbic.201402030
exo-BCN-carbaldehyde
CAS 2166617-41-8, Cat. No EN300-46452840
Synonyms: (1R,8S,9R)-bicyclo[6.1.0]non-4-yne-9-carbaldehyde
Bicyclononyne with a carbonyl functionality is a derivative of the well-known cyclooctyne BCN-OH, EN300-378398. Exo-izomer.
- X. Li, Z. Liu and S. Dong, RSC Adv., 2017, 7, 44470. DOI: 10.1039/C7RA08136G
DIBO
CAS 1027338-06-2, Cat. No EN300-269065
Synonyms: DIBO-OH; tricyclo[10.4.0.0,4,9]hexadeca-1(16),4,6,8,12,14-hexaen-10-yn-2-ol; 3-Hydroxy-1,2:5,6-dibenzocyclooct-7-yne; 4-Dibenzocyclooctynol
4-Dibenzocyclooctynol (DIBO) is a well-known second-generation cyclooctyne. DIBO exhibits fast reaction rates in Strain-Promoted Azide–Alkyne Cycloaddition (SPAAC) and is among the most stable cyclooctynes. In addition to SPAAC, other studied reactions of DIBO include cycloadditions with nitrones and nitrile oxides.
- X. Ning, J. Guo, M. Wolfert and G.-J. Boons, Angew. Chem., Int. Ed., 2008, 47, 2253. DOI: 10.1002/anie.200705456
- M. F. Debets, S. S. van Berkel, J. Dommerholt, A. J. Dirks, F. P. J. T. Rutjes and F. L. van Delft, Acc. Chem. Res., 2011, 44, 805. DOI: 10.1021/ar200059z
- X. Ning, R. Temming, J. Dommerholt, J. Guo, D. Ania, M. Debets, M. Wolfert, G.-J. Boons and F. van Delft, Angew. Chem., Int. Ed., 2010, 49, 3065. DOI: 10.1002/anie.201000408
1-fluorocyclooct-2-yne-1-carboxylic acid
CAS 1227407-73-9; 2219376-60-8 (Li-salt), Cat. No EN300-1072052; EN300-1704293 (Li-salt)
1-Fluorocyclooct-2-yne-1-carboxylic acid is a simple second-generation monofluorocyclooctyne that exhibits moderate reactivity. Its main advantage lies in its minimal structural impact on the studied object.
- D. M. Beal, V. E. Albrow, G. Burslem, L. Hitchen, C. Fernandes, C. Lapthorn, L. R. Roberts, M. D. Selby and L. H. Jones, Org. Biomol. Chem., 2012, 10, 548. DOI: 10.1039/C1OB06398G
- L. Rong, C. Zhang, Q. Lei, H.-L. Sun, S.-Y. Qin, J. Feng and X.-Z. Zhang, Chem. Commun., 2015, 51, 388. DOI: 10.1039/C4CC08396B
- M. K. Schultz, S. G. Parameswarappa and F. C. Pigge, Org. Lett., 2010, 12, 2398. DOI: 10.1021/ol100774p
DBCO-Acid
CAS 1353016-70-2, Cat. No EN300-7393604
Synonyms: DIBAC-Acid; 4-{2-azatricyclo[10.4.0.0,4,9]hexadeca-1(16),4,6,8,12,14-hexaen-10-yn-2-yl}-4-oxobutanoic acid; DIBAC; ADIBO
Dibenzoazacyclooctyne (DBCO) is one of the most reactive (hetero)cyclooctynes in Strain-Promoted Azide–Alkyne Cycloaddition (SPAAC).
A butanoic acid handle is used for conjugation with the target molecule through simple amide coupling.
- L. S. Campbell-Verduyn, L. Mirfeizi, A. K. Schoonen, R. A. Dierckx, P. H. Elsinga and B. L. Feringa, Angew. Chem., Int. Ed., 2011, 50, 11117. DOI: 10.1002/anie.201105547
- S. Manabe, Y. Yamaguchi, K. Matsumoto, H. Fuchigami, T. Kawase, K. Hirose, A. Mitani, W. Sumiyoshi, T. Kinoshita, J. Abe, M. Yasunaga, Y. Matsumura and Y. Ito, Bioconjugate Chem., 2019, 30, 1343. DOI: 10.1021/acs.bioconjchem.9b00132
- H. Echigo, K. Mishiro, M. Munekane, T. Fuchigami, Y. Kitamura, S. Kinuya and K. Ogawa, Bioorg. Med. Chem., 2022, 70, 116919. DOI: 10.1016/j.bmc.2022.116919
DBCO-NHS
CAS 1353016-71-3, Cat. No EN300-7398451
The N-hydroxysuccinimidyl ester of dibenzoazacyclooctyne (DBCO-NHS) is a ready-to-use derivative of DBCO, EN300-7393604.
It can be used for the direct acylation of the target molecule.
- L. S. Campbell-Verduyn, L. Mirfeizi, A. K. Schoonen, R. A. Dierckx, P. H. Elsinga and B. L. Feringa, Angew. Chem., Int. Ed., 2011, 50, 11117. DOI: 10.1002/anie.201105547
- H. E. Murrey, J. C. Judkins, C. W. am Ende, T. E. Ballard, Y. Fang, K. Riccardi, L. Di, E. R. Guilmette, J. W. Schwartz, J. M. Fox and D. S. Johnson, J. Am. Chem. Soc., 2015, 137, 11461. DOI: 10.1021/jacs.5b06847
- H. Echigo, K. Mishiro, M. Munekane, T. Fuchigami, Y. Kitamura, S. Kinuya and K. Ogawa, Bioorg. Med. Chem., 2022, 70, 116919. DOI: 10.1016/j.bmc.2022.116919
Can't find the substance you need? Contact us for custom synthesis solutions!
A well-known bioorthogonal reaction is the Inverse Electron Demand Diels–Alder (IEDDA) cycloaddition between strained alkenes (such as norbornenes, trans-cyclooctenes, and cyclopropenes) and 1,2,4,5-tetrazines (electron-deficient dienes). This reaction is exceptionally fast, does not require a catalyst, and proceeds cleanly in complex biological systems without perturbing the biological milieu.1
The two major applications of strained alkene–tetrazine cycloadditions include: bioconjugation2 (for example, linking small molecules to antibodies or proteins) and click-to-release chemistry (enabling the controlled release of a functional payload upon reaction between tetrazine and trans-cyclooctene).3
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Enamine offers a range of functionalized strained alkenes, including cyclopropenes and trans-cyclooctenes, available from stock. We also provide custom synthesis of strained alkenes designed to meet your specific needs.
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Inverse electron demand Diels–Alder (iEDDA)-initiated conjugation: a (high) potential click chemistry scheme
A.-C. Knall, C. Slugovc, Chem. Soc. Rev. 2013, 42, 5131. DOI: 10.1039/C3CS60049A -
Biomedical applications of copper-free click chemistry: in vitro, in vivo, and ex vivo.
Kim E., Koo H. Chem. Sci. 2019, 10, 7835. DOI: 10.1039/C7CS00184C -
Click to release: instantaneous doxorubicin elimination upon tetrazine ligation
R. M. Versteegen, R. Rossin, W. ten Hoeve, H. M. Janssen, M. S. Robillard Angew. Chem. Int. Ed. 2013,52, 14112–14116. DOI: 10.1002/anie.201305969
[2-methyl-3-(trimethylsilyl)cycloprop-2-en-1-yl]methanol
CAS 29916-92-5, Cat. No EN300-295436
SiMe₃-protected cyclopropenyl methanol serves as a valuable building block for incorporating a cyclopropene moiety into target molecules. Derivatives of this compound exhibit high reaction rates in inverse electron-demand Diels–Alder (IEDDA) reactions with tetrazines. The presence of a methyl group is crucial for maintaining the stability of the cyclopropene unit. The SiMe₃ group functions as a protective group during the synthesis of derivatives and can be readily removed under mild conditions. The hydroxyl group is used as an attachment point through simple chemical transformations.
- A M. Patterson, L. A. Nazarova, B. Xie, D. N. Kamber and J. A. Prescher, J. Am. Chem. Soc., 2012, 134, 18638–18643. DOI: 10.1021/ja3060436
- Yang, J. Šečkutė, C. M. Cole and N. K. Devaraj, Angew. Chem., Int. Ed., 2012, 51, 7476–7479. DOI: 10.1002/anie.201202122
- Yang, Y. Liang, J. Šečkutė, K. N. Houk and N. K. Devaraj, Chem. Eur. J., 2014, 20, 3365–3375. DOI: 10.1002/chem.201304225
{spiro[2.3]hex-1-en-5-yl}methanol
CAS 1621611-39-9, Cat. No EN300-7604414
This strained spirocyclic cyclopropene exhibits enhanced reactivity compared to simpler monocyclic derivatives, both in the IEDDA reaction with tetrazines and as a dipolarophile in the photoinduced cycloaddition with tetrazoles. Its small size and increased water solubility make it an attractive building block for the development of cyclopropene-based probes. The hydroxyl group of the compound is used as an attachment point through simple chemical transformations.
- An, H.-Y.; Wu, T. M.; Lewandowski and Q. Lin, Chem. Commun., 2018, 54, 14005–14008. DOI: 10.1039/C8CC07432A
- Yu and Q. Lin, J. Am. Chem. Soc., 2014, 136, 4153–4156. DOI: 10.1021/ja5012542
- Son, D.; Kim, S.; Kim, W. G.; Byun and S. B. Park, Angew. Chem., Int. Ed., 2025, 64, e202421982. DOI: 10.1002/anie.202421982
(2,3-dimethylcycloprop-2-en-1-yl)methanol
CAS 33283-69-1, Cat. No EN300-7585587
Dimethyl cyclopropene derivatives exhibit enhanced stability both during chemical transformations and in biological environments. Another advantage is the small size of the fragment. On the other hand, they show low to moderate reactivity in the IEDDA reaction with tetrazines. In other words, the balance between stability and reactivity is tipped toward stability. The hydroxyl group of the compound is used as an attachment point through simple chemical transformations.
- Baalmann, L. Neises, S. Bitsch, H. Schneider, L. Deweid, P. Werther, N. Ilkenhans, M. Wolfring, M. J. Ziegler, J. Wilhelm, H. Kolmar and R. Wombacher, Angew. Chem., Int. Ed., 2020, 59, 12885–12893. DOI: 10.1002/anie.201915079
- M. Patterson, L. A. Nazarova, B. Xie, D. N. Kamber and J. A. Prescher, J. Am. Chem. Soc., 2012, 134, 18638–18643. DOI: 10.1021/ja3060436
1-[2-methyl-3-(trimethylsilyl)cycloprop-2-en-1-yl]methanamine hydrochloride
CAS 2172212-79-0 (hydrochloride), 1466419-88-4 (base), Cat. No EN300-1662341
SiMe₃-protected aminomethyl cyclopropene serves as a valuable building block for incorporating a cyclopropene moiety into target molecules. Derivatives of this compound exhibit high reaction rates in inverse electron-demand Diels–Alder (IEDDA) reactions with tetrazines, along with remarkable stability. The presence of a methyl group is crucial for maintaining the stability of the cyclopropene unit. The SiMe₃ group acts as a protective group during the synthesis of derivatives and can be readily removed under mild conditions. The amino group of the compound serves as an attachment point through simple chemical transformations.
- Yang, Y. Liang, J. Šečkutė, K. N. Houk and N. K. Devaraj, Chem. Eur. J., 2014, 20, 3365–3375. DOI: 10.1002/chem.201304225
- Seul, D. Lamade, P. Stoychev, M. Mijic, R. T. Michenfelder, L. Rieger, P. Geng and H.-A. Wagenknecht, Angew. Chem., Int. Ed., 2024, 63, e202403044. DOI: 10.1002/anie.202403044
- Simon, C. Lion, C. Spriet, F. Baldacci-Cresp, S. Hawkins, C. Biot, Angew. Chem. Int. Ed., 2018, 57, 16665. DOI: 10.1002/anie.201808493
2-methylcycloprop-2-ene-1-carboxylic acid
CAS 39492-17-6, Cat. No EN300-118360
A simple cyclopropene carboxylic acid exhibits sluggish reactivity in the IEDDA reaction with tetrazines and o-quinones. Nonetheless, its compact molecular size remains a significant advantage. Incorporation of a methyl group is crucial for achieving an optimal balance between the reactivity and stability of the cyclopropene moiety. The carboxyl group of the compound serves as an attachment point through simple chemical transformations.
- M. Patterson, L. A. Nazarova, B. Xie, D. N. Kamber and J. A. Prescher, J. Am. Chem. Soc., 2012, 134, 18638–18643. DOI: 10.1021/ja3060436
- Yang, J. Šečkutė, C. M. Cole and N. K. Devaraj, Angew. Chem., Int. Ed., 2012, 51, 7476–7479. DOI: 10.1002/anie.201202122
(4E)-cyclooct-4-en-1-ol (TCO-OH; (4E)-4-Cycloocten-1-ol; trans-Cyclooctenol)
CAS 85081-69-2, Cat. No EN300-1609058
The inverse electron-demand Diels–Alder (IEDDA) reaction between trans-cyclooctenes and tetrazines is the fastest known bioorthogonal reaction. 4-TCO-OH is a well-known, highly reactive yet simple dienophile commonly used for bioconjugation.
- Devaraj, S. Hilderbrand, R. Upadhyay, R. Mazitschek and R. Weissleder, Angew. Chem., Int. Ed., 2010, 49, 2869–2872. DOI: 10.1002/anie.200906120
- Baalmann, L. Neises, S. Bitsch, H. Schneider, L. Deweid, P. Werther, N. Ilkenhans, M. Wolfring, M. J. Ziegler, J. Wilhelm, H. Kolmar and R. Wombacher, Angew. Chem., Int. Ed., 2020, 59, 12885–12893. DOI: 10.1002/anie.201915079
Axial-(4E)-cyclooct-4-en-1-ol
CAS: 1018976-14-1 (axial isomer), 85081-69-2 (axial+equatorial isomers), Cat No EN300-21978676
Synonyms: Axial-(4E)-cyclooct-4-en-1-ol; ax-TCO-OH; axial TCO-OH; TCO-OH (axial); axial-(E)-cyclooct-4-enol; rel-(1R,4E,pS)-Cyclooct-4-enol
4-TCO-OH is a well-known, highly reactive yet simple dienophile commonly used for bioconjugation. The axial diastereomer is more reactive in the IEDDA reaction with tetrazines. This compound is commonly used for bioconjugation.
- Rossin, S. M. van den Bosch, W. ten Hoeve, M. Carvelli, R. M. Versteegen, J. Lub and M. S. Robillard, Bioconjugate Chem., 2013, 24, 1210–1217. DOI: 10.1021/bc400153y
- Baalmann, L. Neises, S. Bitsch, H. Schneider, L. Deweid, P. Werther, N. Ilkenhans, M. Wolfring, M. J. Ziegler, J. Wilhelm, H. Kolmar and R. Wombacher, Angew. Chem., Int. Ed., 2020, 59, 12885–12893. DOI: 10.1002/anie.201915079
equatorial-(4E)-cyclooct-4-en-1-ol
CAS: 1018976-12-9 (equatorial diastereomer), 85081-69-2 (axial+equatorial isomers), Cat No EN300-25977034
Synonyms: eq-TCO-OH; TCO-OH (equatorial); equatorial-(E)-cyclooct-4-enol; rel-(1R,4E,pR)-Cyclooct-4-enol
4-TCO-OH is a well-known, highly reactive yet simple dienophile commonly used for bioconjugation. The equatorial diastereomer is less reactive in the IEDDA reaction with tetrazines. Despite this, the compound is still widely used for bioconjugation applications.
- Rossin, S. M. van den Bosch, W. ten Hoeve, M. Carvelli, R. M. Versteegen, J. Lub and M. S. Robillard, Bioconjugate Chem., 2013, 24, 1210–1217. DOI: 10.1021/bc400153y
- Baalmann, L. Neises, S. Bitsch, H. Schneider, L. Deweid, P. Werther, N. Ilkenhans, M. Wolfring, M. J. Ziegler, J. Wilhelm, H. Kolmar and R. Wombacher, Angew. Chem., Int. Ed.,2020, 59, 12885–12893. DOI: 10.1002/anie.201915079
(2E)-cyclooct-2-en-1-ol
CAS: 1414375-00-0, Cat No EN300-45434666
Synonyms: (E)-cyclooct-2-enol; (E)-cyclooct-2-en-1-ol; trans-cyclooct-2-enol; r-TCO; release-TCO;
Trans-cyclooctene, bearing a leaving group in the allylic position, is well known for its ability to eliminate this group following an IEDDA reaction with tetrazines. This property forms the foundation of the click-to-release methodology—a rapidly advancing strategy for prodrug delivery.
- M. Versteegen, R. Rossin, W. ten Hoeve, H. M. Janssen and M. S. Robillard, Angew. Chem., Int. Ed., 2013, 52, 14112–14116. DOI: 10.1002/anie.201305969
- M. Versteegen, W. ten Hoeve, R. Rossin, M. A. R. de Geus, H. M. Janssen and M. S. Robillard, Angew. Chem., Int. Ed.,2018, 57, 10494. DOI: 10.1002/anie.201800402
- J. C. Sarris, T. Hansen, M. A. R. de Geus, E. Maurits, W. Doelman, H. S. Overkleeft, J. D. C. Codée, D. V. Filippov, S. I. van Kasteren, Chem. Eur. J. 2018, 24, 18075. DOI: 10.1002/chem.201803839
(2E)-cyclooct-2-ene-1-carboxylic acid
CAS: 1414375-01-1, Cat No EN300-47214031
A trans-cyclooctene-based carboxylic acid is employed in the click-to-release methodology. A target compound bearing a hydroxyl group can be caged via esterification with this acid and subsequently uncaged following an IEDDA reaction with tetrazines.
- Wu, K. Wu, F. Gaye and M. Royzen, Org. Lett., 2020, 22, 6041–6044. DOI: 10.1021/acs.orglett.0c02129
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C-H Activation Catalysts
C-H activation catalysts are innovate organometallic complexes and organic compounds that enable the direct functionalization of carbon-hydrogen bonds, transforming traditionally inert C-H bonds into reactive sites. Their remarkable ability to modify organic molecules with high precision has significant applications in advanced organic chemistry.
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Chiral Catalysts
Chiral catalysts are specialized molecules or complexes that work as enantioselective catalysts and facilitate asymmetric chemical transformations preferring one of the stereoisomers. These catalysts, including metal-containing complexes with chiral ligands and organic molecules with defined stereochemistry, revolutionized the story of asymmetric synthesis. They provide highly efficient routes to optically pure compounds, which are essential for pharmaceutical development and the production of precise chemicals.
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Cross-Coupling Catalysts
Cross-coupling catalysts, including Buchwald catalysts and precatalysts, are essential organometallic compounds in organic synthesis, enabling the formation of complex molecular structures with high precision through carbon-carbon, carbon-oxygen, and carbon-nitrogen bond formation and others. These catalysts have significantly advanced synthetic chemistry in pharmaceuticals, materials science, and advanced chemical manufacturing.
Buchwald Precatalysts
Buchwald precatalysts are advanced organometallic complexes, primarily based on palladium, designed by Prof. S. Buchwald to facilitate efficient cross-coupling reactions in organic synthesis. These precatalysts are distinguished by their ability to generate active catalytic species in situ, offering enhanced stability, storage, and handling compared to traditional catalysts.
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Other Cross-Coupling Catalysts
Cross-coupling catalysts, including complexes based on nickel (alternative palladium) or other metals, demonstrate varied reactivity, selectivity, and efficiency. They offer diverse capabilities in organic synthesis, enabling the formation of unique C-C, C-N, C-O, and C-S bonds under a wide range of reaction conditions.
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Hydrogenation Catalysts
Hydrogenation catalysts are modified transition metals or their compounds, such as ruthenium, palladium or nickel metalocomplexes, that facilitate the addition of hydrogen to unsaturated organic compounds, enabling key transformations in chemical synthesis.
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Inorganic Catalysts
Inorganic catalysts are powerful materials composed of non-carbon elements that dramatically accelerate chemical reactions while remaining unchanged. These catalysts play a critical role in optimizing industrial processes—from petrochemicals to environmental applications—by enhancing reaction rates and cutting energy costs. With unmatched stability and efficiency, inorganic catalysts are key to driving innovation and sustainability in industries worldwide.
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Low Energy Photoredox Catalysts
Low-energy photoredox catalysts include iridium- and osmium-based complexes that exhibit enhanced photosensitization in the longer-wavelength region compared to conventional photocatalysts. Iridium catalysts are highly effective in sp²-sp³ coupling, decarboxylative arylation and other photoredox transformations, offering versatile reactivity under mild conditions. Osmium catalysts, on the other hand, serve as powerful sensitizing agents in biochemical and medical research, enabling precise photoactivation in biological systems. Additionally, this category features two biotin-conjugated molecules designed for use alongside osmium catalysts in targeted studies, further expanding their applications in bioanalytical research.
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Metathesis Catalysts
Metathesis catalysts, particularly ruthenium-based complexes such as Grubbs and Hoveyda-Grubbs catalysts, represent a groundbreaking advancement in organic synthesis by enabling the redistribution of carbon-carbon double bonds. These exceptional catalysts function via a unique mechanism involving metal-carbene intermediates, facilitating a wide range of transformations, including ring-closing metathesis (RCM), cross-metathesis (CM), and ring-opening metathesis polymerization (ROMP).
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N-Heterocyclic Carbene (NHC) Complexes
N-Heterocyclic Carbene (NHC) complexes are advanced chemical compounds featuring a central carbene unit, which is bonded to a heterocyclic ring structure. Known for their exceptional stability and reactivity,facilitating a wide range of catalytic reactions. These complexes are widely utilized in organic synthesis, pharmaceuticals, and materials science, enabling more efficient reactions with minimal side products and improved selectivity.
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Organocatalysts
Organocatalysts are small organic molecules that effectively catalyze chemical reactions without requiring metal centers, offering unique advantages in asymmetric synthesis and green chemistry. These catalysts, including various organonitrogen, organophosphorus, and other compounds, enable stereoselective transformations with high efficiency and minimal environmental impact.
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Photoredox Catalysts
Photocatalysts are specialized compounds that harness light energy to facilitate chemical transformations. These catalysts include a wide range of organic molecules and metal complexes, such as those containing ruthenium(II) and iridium(III). They enable unique reaction pathways through single-electron transfer (SET) processes and the generation of reactive intermediates under mild conditions, making them particularly valuable in environmentally friendly chemistry.
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Transition Metal Catalysts
Transition metal catalysts, including complexes of copper, iron, cobalt, and other metals, are essential for a wide range of chemical transformations in both industrial and laboratory settings. They are especially important in hydroformylation reactions, oxidation processes, and polymerization, with broad applications in pharmaceutical synthesis, materials science, and large-scale chemical production.
Buchwald Ligands
Buchwald ligands are sterically hindered and electron-rich phosphine compounds belonging to the class of dialkylbiarylphosphines. They are highly effective in various palladium-catalyzed cross-coupling reactions and enable exceptional catalytic activity and stability under mild reaction conditions, particularly in challenging C-N, C-O, and other bond formations. The systematic modification of their biaryl backbone and phosphine substituents allows fine-tuning of their electronic and steric properties, making them valuable tools for process and method development in academic and industrial settings.
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Cross-Coupling Ligands
Specialized organic molecules that facilitate metal-catalyzed coupling reactions. By binding to metal centers, these ligands enhance catalyst stability and regulate reaction selectivity. Common examples include phosphines and N-heterocyclic carbenes, which are indispensable in Suzuki, Buchwald-Hartwig, and other cross-coupling reactions widely employed in pharmaceutical development and materials synthesis
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Ligands for Asymmetric Catalysis
Ligands for asymmetric catalysis include both chiral and non-chiral molecules that create specific three-dimensional environments around metal centers, facilitating the synthesis of enantiomerically pure compounds. These ligands are essential in asymmetric catalysis as they influence the spatial arrangement of reactants, guiding the course of enantioselective reactions and promoting the preferential formation of the desired stereoisomers.
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Ligands for C-H Activation
Molecules that facilitate the selective functionalization of traditionally unreactive carbon-hydrogen bonds, by stabilizing metal catalysts and directing their activity toward specific C-H bonds. These ligands enable precise control over pathways of the C-H bond functionalization. Their distinctive electronic and steric properties render them indispensable tools in contemporary organic synthesis.
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Ligands for Ullmann Сross-Сoupling
Ligands for Ullmann cross-coupling are organic molecules that facilitate C(sp²)-N and C(sp²)-O bond formation under copper catalysis at ambient temperature. These ligands offer a cost-effective alternative to conventional phosphine ligands and palladium catalysts commonly used in Buchwald-Hartwig cross-coupling reactions. By stabilizing copper intermediates and enhancing catalytic efficiency, they enable milder reaction conditions while maintaining high yields and selectivity. Their applications extend across various industries, including pharmaceuticals, agrochemicals, and advanced materials, where selective heteroatom coupling plays a critical role in molecular design.
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N-Heterocyclic Carbene (NHC) Ligands
Cyclic compounds characterized by a divalent carbon atom situated between two nitrogen atoms, enabling the formation of exceptionally strong bonds with metal centers. These molecules exhibit superior thermal stability and distinctive electronic properties compared to phosphine ligands, making them indispensable in cross-coupling reactions, olefin metathesis, and a wide range of transformations in organic synthesis. Their modular design allows for precise tuning of steric and electronic properties through structural modifications, further enhancing their versatility.
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Other Phosphine Ligands
Phosphine ligands are organophosphorus compounds that play an important role in transition metal catalysis by modulating the electronic and steric properties of metal centers. These versatile ligands form stable metal-phosphorus bonds via their lone pair of electrons, enabling precise control over catalyst reactivity and selectivity. Their tunable nature, achieved through variations in substituents on the phosphorus atom, makes them indispensable tools in modern organic synthesis and catalytic processes.
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Photoredox Ligands
Light-sensitive molecules that facilitate electron transfer in catalytic processes. They absorb visible light to form excited states, enabling single-electron transfer (SET) pathways. This allows for mild and selective organic transformations. Photoredox chemistry becomes increasingly relevant, offering environmentally friendly and mild reaction conditions while enabling complex transformations, such as C–C bond formation, oxidative couplings, and radical-mediated processes, that are challenging to achieve using conventional methods.
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Ligands for Other Types of Catalysis
Ligands for various types of catalysis, designed to support broad applications in research and industry. They enable enhanced reactivity and selectivity in processes ranging from organic synthesis to materials development. A versatile choice for advancing catalytic performance across diverse chemical transformations.