Journal of the American Chemical Society p. 16388 - 16397 (2019)
Update date:2022-08-04
Topics:
Wu, Zhi-Chen
Boger, Dale L.
Herein we disclose the synthesis and full characterization of the first monocyclic aromatic 1,2,3,5-tetrazine, 4,6-diphenyl-1,2,3,5-tetrazine. Initial studies of its cycloaddition reactivity, mode, regioselectivity, and scope illustrate that it participates as the 4π-component of well-behaved inverse electron demand Diels-Alder reactions where it preferentially reacts with electron-rich or strained dienophiles. It was found to exhibit an intrinsic reactivity comparable to that of the isomeric 3,6-diphenyl-1,2,4,5-tetrazine, display a single mode of cycloaddition with reaction only across C4/N1 (no N2/N5 cycloaddition observed), proceed with a predictable regioselectivity (dienophile most electron-rich atom attaches to C4), and manifest additional reactivity complementary to the isomeric 1,2,4,5-tetrazines. It not only exhibits a remarkable cycloaddition reactivity, surprisingly good stability (e.g., stable to chromatography, long-term storage, presence of H2O even as reaction co-solvent), and broad cycloaddition scope, but it also displays powerful orthogonal reactivity with the 1,2,4,5-tetrazines. Whereas the latter reacts at extraordinary cycloaddition rates with strained dienophiles (tetrazine ligation), the new and isomeric 1,2,3,5-tetrazine displays similarly remarkable cycloaddition rates and efficiencies with amidines (1,2,3,5-tetrazine/amidine ligation). The crossover reactivities (1,2,4,5-tetrazines with amidines and 1,2,3,5-tetrazines with strained dienophiles) are sufficiently low to indicate they may be capable of use concurrently without competitive reactions.
View MoreShanghai Run-Biotech Co., Ltd.
website:http://www.run-biotech.com
Contact:+86-21-31576854/57171705 / 57171706
Address:second floor, building 3, No.999, jiangyue Road, minghang District, Shanghai, China
Taizhou Crene Biotechnology co.ltd
Contact:86-576-88813233 88205808
Address:Economic Developed Zone of Taizhou Zhejiang China
Contact:+86-25-85281586
Address:13F,Bld2#,South of Longpan Road
Anhui Redstar Pharmaceutical Corp., Ltd
Contact:+86-563-5120837
Address:Jingxian Industrial Development Zone, Anhui , China
Hefei TNJ chemical industry co.,ltd
website:https://www.tnjchem.com
Contact:+86-551-65418695
Address:B911 Xincheng Business Center, Qianshan Road, Hefei Anhui China
Doi:10.1063/1.464633
(1993)Doi:10.1021/jm00121a015
(1989)Doi:10.1246/bcsj.61.441
(1988)Doi:10.1039/c9ob01797f
(2019)Doi:10.1002/ejoc.200900106
(2009)Doi:10.1016/j.tet.2009.04.022
(2009)