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Synthesis of quinoxalinones

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Benzimidazoles and quinoxalin-2(1H)-ones were synthesized by treatment of 2-(N-Boc-amino)phenyl­isocyanide with carboxylic acids and glyoxylic acids, respectively via two-component coupling, deprotection, and intermolecular cyclization.
Z.-Z. Chen, Y. Tang, L. Zuo, D.-Y. Tang, J. Zhang, Z.-G. Xu, Synlett, 2014, 25, 2518-2520.

Efficient reactions of α-keto acids with 2-aminobenzamides, 2-aminobenzenethiols, benzene-1,2-diamines, and 2-aminophenols provide quinazolinones, benzothiazoles, quinoxalinones, and benzoxazinones under catalyst-free conditions, using water as the solvent. Products can be easily purified through filtration and washing with ethanol (or crystallized).
J. Huang, W. Chen, J. Liang, Q. Yan, Y. Fan, M.-W. Chen, Y. Peng, J. Org. Chem., 2021, 86, 14866-14882.

Excited-state palladium-catalyzed alkylative cyclizations of acrylamides and alkylations of quinoxalinones exhibit wide scope, occur under mild conditions, and furnish products in excellent yields. Various primary, secondary, and tertiary unactivated alkyl halides can serve as alkyl radical precursors.
G. C. Upreti, T. Singh, K. Khanna, A. Singh, J. Org. Chem., 2023, 88, 4422-4433.

Photoredox catalysis enables a direct alkylation of a range of quinoxalinones with alkylborates to provide a variety of 3-alkyl quinoxalinones in very good yields. The practicality of this protocol was demonstrated by the concise synthesis of a potential bioactive nonpeptide angiotensin II receptor antagonist.
W. Zhao, Y. Zhang, S. Yuan, X. Yu, L. Liu, J. Li, J. Org. Chem., 2023, 88, 6218-6226.

The combination of organophotoredox catalysis with hydrogen atom transfer enables a mild C-H alkylation of quinoxalin-2(1H)-ones with feedstock aldehydes, amides, alcohols, ethers, or cycloalkanes. This reaction occurred under environmentally benign and external oxidant-free reaction conditions with good functional group compatibility.
L. Wang, Z. Chen, G. Fan, X. Liu, P. Liu, J. Org. Chem., 2022, 87, 14580-14587.

The semi-heterogeneous g-C₃N₄/NaI dual system catalyzes a C-C bond formation between quinoxalin-2(1H)-ones and arylhydrazines under blue light irradiation to provide a wide range of 3-arylquinoxaline-2(1H)-ones in high yields with excellent functional group tolerance.
H.-Y. Song, M.-Y. Liu, J. Huang, D. Wang, J. Jiang, J.-Y. Chen, T.-B. Yang, W.-M. He, Green Chem., 2023, 25, 3292-3296.

A photoredox-catalyzed direct arylation of quinoxalin-2-(1H)-ones using diaryliodonium triflates as convenient, stable, and cheap aryl sources provides efficient access to a wide variety of pharmaceutically important 3-arylquinoxalin-2-(1H)-ones. This operationally simple method offers mild conditions, broad scope, scalability, and high functional group tolerance.
R. K. Samanta, P. Meher, S. Murarka, J. Org. Chem., 2022, 87, 10947-10957.

The combination of tert-butyl hypochlorite, tetrabutylammonium iodide and tetrabutylammonium chloride as oxidation system enables the transformation of ethyl 2-(N-arylcarbamoyl)-2-iminoacetates into the corresponding quinoxalinones in high yield. Oxygen exhibits a beneficial effect on the reaction.
D. Li, Y. Li, W. Yu, Synthesis, 2017, 49, 4283-4291.

Whereas the cyclocondensation of 2-aminothiophenols with 1,2-biselectrophiles such as ethyl glyoxalate and diethyl oxalate in aqueous medium leads to the formation of benzothiazole-2-carboxylates via a 5-endo-trig process contrary to Baldwin’s rule, the reaction of 2-aminophenols/anilines produced the corresponding benzazine-3-ones or benzazine-2,3-diones via a 6-exo-trig process in compliance with Baldwin’s rule.
T. M. Dhameliya, S. S. Chourasiya, E. Mishra, P. S. Hadhavar, P. V. Bharatam, A. K. Chakraborti, J. Org. Chem., 2017, 82, 10077-10091.

Complexes of pyridyl glycosyl triazoles with Cu(I) salts were explored as efficient catalysts to successfully assemble 2-amino-3-substituted and 3-substituted quinazolinones by domino/tandem cross-coupling reactions of various N-substituted o-halobenzamides with cyanamide and formamide, respectively.
S. K. Singh, S. Kumar, M. S. Yadav, V. K. Tiwari, J. Org. Chem., 2022, 87, 15389-15402.

An efficient, photoredox-catalyst-free radical alkylation of quinoxalin-2(1H)-ones with photoexcited 4-alkyl-1,4-dihydropyridines (R-DHPs) as alkyl radical precursors and acetoxybenziodoxole (BI-OAc) as an electron acceptor offers benign reaction conditions and good functional group compatibility.
X.-K. He, J. Lu, A.-J. Zhang, Q.-Q. Zhang, G.-Y. Xu, J. Xuan, Org. Lett., 2020, 22, 5984-5989.

A tandem nitrosation/cyclization reaction of N-aryl cyanoacetamides with tert-butyl nitrite provides quinoxalin-2-ones in good yields with good functional group tolerance. The dehydrogenative N-incorporation is achieved through a sequence of nitrosation, tautomerization, and cyclization.
F. Wang, B.-L. Hu, L. Liu, H.-Y. Tu, X.-G. Zhang, J. Org. Chem., 2017, 82, 11247-11252.

Selectfluor promotes an oxidative coupling of quinoxalin-2(1H)-ones with alcohols, amines, thiols at the C3-position under metal- and photocatalyst-free conditions. The method offers a broad substrate scope including bioactive molecules, mild reaction conditions, readily available coupling partners, high yields, scalability and step-economy.
Sonam, V. N. Shinde, K. Rangan, A. Kumar, J. Org. Chem., 2023, 88, 2344-2357.

A facile and effective alkoxylation of quinoxalin-2(1H)-ones with primary or secondary alcohols via cross-dehydrogenative coupling under catalyst-free conditions provides 3-alkoxylquinoxalin-2(1H)-ones in very good yields in the presence of PhI(OTFA)₂ as oxidant.
Q. Yang, X. Han, J. Zhao, H.-Y. Zhang, Y. Zhang, J. Org. Chem., 2019, 84, 11417-11424.

An efficient visible-light-induced C(sp²)-H/N-H cross-dehydrogenative coupling (CDC)-amination with both primary and secondary aliphatic amines allows the direct formation of 3-aminoquinoxalin-2(1H)-ones. Preliminary mechanistic studies reveal that the reaction proceeds through a radical process.
W. Wei, L. Wang, P. Bao, Y. Shao, H. Yue, D. Yang, X. Yang, X. Zhao, H. Wang, Org. Lett., 2018, 20, 7125-7130.

An efficient visible-light-induced decarboxylative coupling reaction of N-protected α-amino acids with heterocycles provides aminoalkylated heterocycles in good yields. Attractive features of this process include the generation of aminomethyl radical by an inexpensive organic photocatalyst under transition-metal-free conditions.
Y. Li, C. Dai, S. Xie, P. Liu, P. Sun, Org. Lett., 2021, 23, 5906-5910.

Complexes of pyridyl glycosyl triazoles with Cu(I) salts were explored as efficient catalysts to successfully assemble 2-amino-3-substituted and 3-substituted quinazolinones by domino/tandem cross-coupling reactions of various N-substituted o-halobenzamides with cyanamide and formamide, respectively.
S. K. Singh, S. Kumar, M. S. Yadav, V. K. Tiwari, J. Org. Chem., 2022, 87, 15389-15402.

A metal-free cross-dehydrogenative coupling between quinoxalinones and amines in the presence of catalytic iodine and aqueous tert-butyl hydroperoxide as the terminal oxidant provides 3-aminoquinoxalinones in good yields in dioxane as solvent. The reaction is highly versatile and exhibits good functional group tolerance with a range of primary and secondary amines.
A. Gupta, M. S. Deshmuk, N. Jain, J. Org. Chem., 2017, 82, 4748-4792.

The use of trifluoromethyl thianthrenium salts enables high-yielding and scalable trifluoromethylation reactions under visible light irradiation. A free radical homolytic process is involved in this reaction, generating a key trifluoromethyl radical intermediate.
Y. Li, X. Liang, K. Niu, J. Gu, F. Liu, Q. Xia, Q. Wang, W. Zhang, Org. Lett., 2022, 24, 5918-5923.