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Synthesis of Chromones and Flavones

Recent Literature

A highly efficient and selective palladium-catalyzed ligand-free cyclocarbonylation reaction of o-iodophenols with terminal acetylenes under atmospheric CO pressure affords diversified chromones in very good yields. The use of a phosphonium salt ionic liquid as the reaction medium enhances the efficiency of the cyclocarbonylation reaction.
Q. Yang, H. Alper, J. Org. Chem., 2010, 75, 948-950.

A palladium complex of 1,3,5,7-tetramethyl-2,4,8-trioxa-6-phenyl-6-phosphaadamantane is an effective catalyst for a sequential microwave-assisted Sonogashira and carbonylative annulation reaction to give substituted flavones.
E. Awuah, A. Capretta, Org. Lett., 2009, 11, 3210-3213.

E. Awuah, A. Capretta, Org. Lett., 2009, 11, 3210-3213.

A Pd-catalyzed copper-free carbonylative Sonogashira coupling reaction at room temperature was achieved by using water as a solvent under balloon pressure of CO with Et₃N as a base. The developed method was successfully applied to the synthesis of flavones.
B. Liang, M. Huang, Z. You, Z. Xiong, K. Lu, R. Fathi, J. Chen, Z. Yang, J. Org. Chem., 2005, 70, 6097-6100.

The reaction of the silyl ester of O-acyl(aroyl)salicylic acids and (trimethylsilyl)methylenetriphenylphosphorane provides acylphosphoranes, which undergo intramolecular Wittig cyclization on the ester carbonyl to afford 4H-chromen-4-ones in very good yields.
P. Kumar, M. S. Bodas, Org. Lett., 2000, 2, 3821-3823.

Formation of enamino ketones from 1-(2-hydroxyphenyl)ethanone derivatives under microwave heating followed by cyclization using T3P® provides 4H-chromene-4-ones in short reaction times and high purity.
C. Balakrishna, V. Kandula, R. Gudipati, S. Yennam, P. U. Devi, M. Behera, Synlett, 2018, 29, 1087-1091.

A MCM-41-immobilized bidentate phosphine palladium complex catalyzes an efficient carbonylative cyclization of aryl iodides and 2-hydroxyacetophenones under 3 bar of carbon monoxide in the presence of DBU in DMSO at 120°C to provide a wide variety of flavones in very good yields. The supported palladium catalyst can be easily recovered via centrifugation and recycled more than nine times.
G. Xie, J. Zhang, M. Cai, B. Huang, Synthesis, 2023, 55, 647-656.

The combination of iron(III)chloride, tert-butyl nitrite (TBN), and N-hydroxyphthalimide (NHPI) catalyzes a direct aerobic α,β-dehydrogenation of carbonyls. A large variety of lactams and flavanones as well as coumarin and thiochromen-4-one could be produced via this transition-metal-free method in high yields.
G.-Q. Jiang, B.-H. Han, X.-P. Cai, J.-P. Qu, Y.-B. Kang, Org. Lett., 2023, 25, 4429-4433.

Arylation of ortho-hydroxyarylenaminones by vast diversities of bench-stable and easy-to-use sulfonium salts and arenesulfonyl chlorides enables a straightforward synthesis of 3-arylchromones in very good yields. Light-mediated photoredox as well as electrophilic arylation showed good efficiency.
S. Mkrtchyan, V. O. Iaroshenko, J. Org. Chem., 2021, 86, 4896-4916.

Arylation of ortho-hydroxyarylenaminones by vast diversities of bench-stable and easy-to-use sulfonium salts and arenesulfonyl chlorides enables a straightforward synthesis of 3-arylchromones in very good yields. Light-mediated photoredox as well as electrophilic arylation showed good efficiency.
S. Mkrtchyan, V. O. Iaroshenko, J. Org. Chem., 2021, 86, 4896-4916.

A consecutive domino arylation of ortho-hydroxyarylenaminones with in situ photogenerated aryl radicals provides 3-aryl-substituted chromones (isoflavones) in very good yields. Notably, the photo-Meerwein arylation of aryl diazonium tetrafluoroborates demonstrated high efficiency.
S. Mkrtchyan, V. O. Iaroshenko, Chem. Commun., 2020, 57, 2606-2609.

The carbonyl β-C(sp³)-H bond hydrogens of ortho-acyl phenols could be substituted by intramolecular phenolic hydroxyls to form O-heterocycles. A subsequent dehydrogenation provides flavonoids. This oxidant-free cascade reaction is catalyzed by Pd/C.
X. Zhao, J. Zhou, S. Lin, X. Jin, R. Liu, Org. Lett., 2017, 19, 976-979.

A one-pot Friedel-Crafts acylation of alkynes with suitably substituted benzoyl chlorides provides chromenones and thiochromenones. The ready availability of both starting materials, alkynes and benzoyl chlorides, coupled with the experimental simplicity makes the current synthetic method to (thio)chromenones fast, efficient, and practical.
H. Y. Kim, E. Song, K. Oh, Org. Lett., 2017, 19, 312-315.

The use of transition-metal catalysts and TEMPO enables an efficient synthesis of 2-phenyl-4H-chromen-4-one, 2-phenylquinolin-4(1H)-one, and 11H-benzofuro[3,2-b]chromen-11-one derivatives in good yields from 2'-hydroxychalcones, 2'-aminochalcones, and 3-hydroxyflavones, respectively. The methods offer high atom-economy, use of benign solvent and auxiliaries, and easy handling.
A. Singh, S. Singh, K. Ghosh, N. Ahmed, Synthesis, 2023, 55, 4191-4203.

Chromone derivatives were synthesized from 2,3-allenoic acids and benzynes in good yields under mild conditions. The benzyne intermediate undergoes 1,2-addition with the carbonyl group, followed by ring opening, conjugate addition, and protonolysis to afford chromone derivatives. This protocol allows the diversity due to the substituent-loading capability of 2,3-allenoic acids as well as benzynes.
G. Chai, Y. Qiu, C. Fu, S. Ma, Org. Lett., 2011, 13, 5196-5199.

A regioselective rhodium(III)-catalyzed oxidative C-H activation/annulation of salicylaldehydes with propargylic acetates provides 3-vinyl chromones in good yields with broad functional group tolerance. 3-Vinyl chromones were converted into biologically active benzo[c]xanthones by I₂-mediated oxidative electrocyclization.
B. Li, J. Zhu, X. Zheng, W. Ti, Y. Huang, H. Yao, J. Org. Chem., 2023, 88, 548-558.

A facile one-pot transformation of 2-fluoroacetophenones provides chromone-2-carboxylates in a single step via a tandem C-C and C-O bond formation. This methodology can serve as a promising alternative tool for finding new bioactive chromones with diverse modifications due to the opportunity to use new raw materials.
S. Tummanapalli, S. K. Punna, K. C. Gulipalli, S. Endoori, S. Bodige, A. K. Pommidi, S. Medaboina, S. Choppadandi, R. Boya, V. K. Ganapathi, D. Y. Mamindla, R. Konakalla, G. K. Bodala, M. R. Bakangari, S. D. Kottam, D. Jarikote, T. Potewar, M. Valluri, J. Org. Chem., 2023, 88, 8387-8399.

A Rh(III)-catalyzed annulation between salicylaldehydes and diazo compounds offers good functional group tolerance, scalability, and a controllable chemoselectivity. AgNTf₂ as additive favored benzofurans via a tandem C-H activation/decarbonylation/annulation process, while AcOH led to chromones through a C-H activation/annulation pathway.
P. Sun, S. Gao, C. Yang, S. Guo, A. Lin, H. Yao, Org. Lett., 2016, 18, 6464-6467.

The unusual alcohol mediated reaction of 4-hydroxycoumarins and β-nitroalkenes leads to 4-oxo-2-aryl-4H-chromene-3-carboxylate (flavone-3-carboxylate) derivatives. The transformation occurs via the in situ formation of a Michael adduct, followed by the alkoxide ion mediated rearrangement of the intermediate. The effects of different media on the reaction were investigated.
M. R. Zanwar, M. J. Raihan, S. D. Gawande, V. Kavala, D. Janreddy, C.-W. Kuo, R. Ambre, C.-F. Yao, J. Org. Chem., 2012, 77, 6495-6504.

A facile and effective tandem reaction of ynones and methyl salicylates provides a broad range of 3-acyl chromones in good yields. This protocol offers easily accessible substrates, broad substrate scope, and high regioselectivity under mild and transition-metal-free conditions.
Y.-F. Ye, F. Li, J.-L. Chen, Z.-Q. An, G.-Y. Zhang, Y.-B. Wang, J. Org. Chem., 2022, 87, 14005-14015.

Reactions between readily available o-hydroxyphenyl enaminones and various alkenes enable a a step economical and general synthesis of 3-vinyl chromones.
L. Fu, Z. Xu, J.-P. Wan, Y. Liu, Org. Lett., 2020, 22, 9518-9523.

Visible light induces an efficient and facile 3-alkyl chromone synthesis from easily accessible o-hydroxyaryl enaminones and α-diazo esters under mild conditions. This additive-free method provides excellent yields with a broad substrate scope at room temperature, tolerating various functional groups.
W. Zhao, Z. He, X. Yang, Y. Yu, J. B. Baell, F. Huang, J. Org. Chem., 2023, 88, 13634-13644.

A mild ICl-induced cyclization of heteroatom-substituted alkynones provides a simple, highly efficient approach to various 3-iodochromones, iodothiochromenones, iodoquinolinones and analogues in good to excellent yields. Subsequent palladium-catalyzed transformations afford a rapid increase in molecular complexity.
C. Zhou, A. V. Dubrovsky, R. C. Larock, J. Org. Chem., 2006, 71, 1626-1632.

An efficient cyclization of enamino ketones in the presence of Selectfluor provides various 3-fluorochromones (3-fluoro-4H-chromene-4-ones) in good yields. This method offers simple operational procedures, a high purity of the product, and excellent regioselectivity.
V. Kandula, P. K. Thota, P. Mallesham, K. Raghavulu, A. Chatterjee, S. Yennam, M. Behera, Synlett, 2019, 30, 2295-2299.

The use of the Langlois reagent enables an efficient and regioselective synthesis of various 3-(trifluoromethyl)chromones from enamino ketones. This convenient procedure offers high product purity and yield.
P. Thota, K. Sheelam, S. Kottawar, K. Shivakumar, M. Kaliyaperumal, S. Yennam, M. Behera, Synlett, 2022, 33, 1660-1664.

The use of aroyl peroxides as coupling partners enables a direct acyloxylation of the α-C(sp²)-H bond in tertiary β-enaminones under catalyst-free conditions and ambient temperature via a thermoinduced free-radical pathway. The present method offers an efficient synthesis of both acyloxylated chromones and enaminones.
Y. Guo, Y. Xiang, L. Wei, J.-P. Wan, Org. Lett., 2018, 20, 3971-3974.

A Baker-Venkataraman rearrangement followed by a quick cyclization-dehydration step and a saponification provides flavonols in good yields.
A. Fougerousse, E. Gonzalez, R. Brouillard, J. Org. Chem., 2000, 65, 583-586.

A photoredox-catalyzed intermolecular tandem sulfonamination/cyclization of enaminones with N-aminopyridinium salts as the sulfonaminated reagents provides 3-sulfonaminated chromones without transition-metal catalysts or bases. The reaction exhibits a broad scope and good functional group tolerance, good yields, and regioselectivity.
W. Hu, X. Diao, J. Yuan, W. Liang, W. Yang, L. Yang, J. Ma, S. Zhang, J. Org. Chem., 2024, 89, 644-655.

Iodine mediates an efficient synthesis of functionalized 2-(methylthio)-4H-chromen-4-ones by intramolecular cyclization of easily accessible 1-(2-benzyloxy-aryl)-3,3-bis-methylsulfanyl-propenones. 3-Halo-2-(methylthio)-4H-chromen-4-ones can be synthesized via various two- or one-pot halogenation approaches.
A. Elagamy, R. Shaw, C. Shah, R. Pratap, J. Org. Chem., 2021, 86, 9478-9489.