Categories: Synthesis of N-Heterocycles > benzo-fused N-Heterocycles >
Synthesis of isatins
An I2/TBHP-mediated oxidation of commercially available indoles affords isatins in moderate to good yields.
Y. Zi, Z.-J. Cai, S.-Y. Wang, S.-J. Ji, Org. Lett., 2014, 16, 3094-3097.
The reagent mixture NaI/IBX-SO3K, containing a sulfonylated derivative of 2-iodoxybenzoic acid, was employed for an oxidative direct conversion of indoles into isatins. A synthetic route toward IBX-SO3K and the X-ray crystal structure of the reagent are presented.
A. Bredenkamp, F. Mohr, S. F. Kirsch, Synthesis, 2015, 47, 1937-1943.
A convenient oxidation of oxindoles with molecular oxygen in the presence of tert-butyl nitrite as an additive enables a mild and metal-free synthesis of isatins without the need for any catalyst or base.
W.-T. Wei, W.-W. Ying, W.-M. Zhu, Y. Wu, Y.-L. Huang, Y.-Q. Cao, Y.-N. Wang, H. Liang, Synlett, 2017, 28, 2307-2310.
Recombination of alkyl radicals derived from indolin-2-ones with the tert-butylhydroperoxy radical affords 3-(tert-butylperoxy)indolin-2-one intermediates that can be further transformed into indoline-2,3-diones under air. This strategy provides a simple, effcient, and metal-free route to indolinediones.
W.-W. Ying, W.-M. Zhu, H. Liang, W.-T. Wei, Synlett, 2018, 29, 215-218.
The use of a catalytic amount I2 and TBHP as stoichiometric oxidant enables a simple and atom economic one-pot synthesis of isatins from 2′-aminoacetophenones via oxidative amido cyclization of the sp3 C-H bond. In the presence of a stoichiometric amount of iodine, the reaction yields iodoisatines. The reaction proceeds through sequential iodination, Kornblum oxidation, and amidation in one pot.
A. Ilangovan, G. Satish, J. Org. Chem., 2014, 79, 4984-4991.
Cross-dehydrogenative C-N annulations and dealkylative C-N annulations of 2′-N-aryl/alkylaminoacetophenones and 2′-N,N-dialkylaminoacetophenones respectively in the presence of Cu(OAc)2ĚH2O, NaOAc and air gave isatins in good yields. However, on reaction with CuBr, 2′-N-benzylaminoacetophenones underwent selective oxidation at the benzylic position to provide the corresponding benzamides exclusively.
A. Ilanovan, G. Satish, Org. Lett., 2013, 15, 5726-5729.
An electrochemical oxygenation of indoles provides isatins by merging with a complementary cathode oxygen reduction reaction. This green protocol uses molecular oxygen as the sole oxidant, is free of an an electron transfer mediator, and enables gram-scale preparation.
W. Zhuang, J. Zhang, C. Ma, J. S. Wright, X. Zhang, S.-F. Ni, Q. Huang, Org. Lett., 2022, 24, 4229-4233.
A simple electrochemical oxidation of 2'-aminoacetophenones in the presence of n-Bu4NI provides various isatins with moderate to good yields via C(sp3)-H oxidation followed by intramolecular C-N bond formation. A radical-based pathway is proposed.
P. Qian, J.-H. Su, Y. Wang, M. Bi, Z. Zha, Z. Wang, J. Org. Chem., 2017, 82, 6434-6440.
Molecular iodine promoted an efficient synthesis of isatins from 2′-aminophenylacetylenes, 2′-aminostyrenes, and 2′-amino-β-ketoesters via oxidative amidation. The reaction involves iodination, followed by Kornblum oxidation, and intramolecular amidation in one pot.
G. Satish, A. Polu, T. Ramar, A. Ilangovan, J. Org. Chem., 2015, 80, 5167-5175.
An efficient and environmentally friendly conversion of α-hydroxy N-arylamides into isatins in very good yields proceeded smoothly under metal-free conditions in the presence of hydrogen peroxide as oxidant. This convenient method offers broad substrate scope.
J. Li, X. Cheng, X. Ma, G. Lv, Z. Zhan, M. Guan, Y. Wu, Synlett, 2016, 27, 2485-2488.
Isatins can be synthesized from α-formyl amides in good yields via one-pot intramolecular cyclization-oxidation reaction in the presence of pyridinium chlorochromate (PCC). The reaction proceeded smoothly under air, offers a broad substrate scope, and is operationally simple.
Q. Yue, Y. Wang, L. Hai, L. Guo, H. Yin, Y. Wu, Synlett, 2016, 27, 1292-1296.