Base-Catalyzed Synthesis of Flavones via Thiol-Assisted Sequential Demethylation/Cyclization of 1-(2-Methoxyphenyl)prop-2-yn-1-ones

Abstract

Flavone and analogues represent an important class of biologically and pharmacologically active substances commonly found in the composition of diverse plants as part of the class of secondary metabolites. Herein, an efficient and regioselective synthetic strategy for the preparation of functionalized flavones is demonstrated through sequential demethylation/6-endo-dig intramolecular cyclization of propyn-1-ones, using catalytic amounts of base in the presence of a thiol, by employing NMP as the solvent. The reactions proceeded smoothly under transition-metal-free and open to air conditions, furnishing the desired six-membered heterocycles in moderate to excellent yields, in short reaction time.

Key words

flavones - demethylation - cyclization - base-catalysis - thiols

Publication History

Received: 03 March 2022

Accepted after revision: 13 June 2022

Accepted Manuscript online:
13 June 2022

Article published online:
20 July 2022

• References

• 1a Alsharairi NA. Int. J. Environ. Res. Public Health 2021; 18: 5243
• 1b Olennikov DN, Chirikova NK. Chem. Nat. Compd. 2021; 57: 436
• 1c Albouchi F, Avola R, Dico GM. L, Calabrese V, Graziano AC. E, Abderrabba M, Cardile V. Molecules 2018; 23: 2526
• 2 Nijveldt R, Nood EV, Hoorn DE. C. V, Boelens PG, Norren KV, Leeuwen PA. M. V. Am. J. Clin. Nutr. 2001; 74: 418
• 3a Reis J, Gaspar A, Milhazes N, Borges F. J. Med. Chem. 2017; 60: 7941
• 3b Singh M, Kaur M, Silakari O. Eur. J. Med. Chem. 2014; 84: 206
• 4 Reséndiz MF, Oliveras PL, Rubalcava ML. M. Appl. Microbiol. Biotechnol. 2021; 105: 4225
• 5 Chumkaew P, Srisawat T. Chem. Nat. Compd. 2021; 57: 274
• 6 Abo-Salem HM, Gibriel AA, El Awady ME, Mandour AH. Med. Chem. 2021; 17: 158
• 7 Hida T, Tamiya M, Nishio M, Yamamoto N, Hirashima T, Horai T, Tanii H, Shi MM, Kobayashi K, Horio Y. Cancer Sci. 2011; 102: 845
• 8 Wang B, Qu J, Luo S, Feng S, Li T, Yuan M, Huang Y, Liao J, Yang R, Ding C. Molecules 2018; 23: 2513
• 9 Wu X, Song M, Gao Z, Sun Y, Wang M, Li F, Zheng J, Xiao H. J. Nutr. Biochem. 2017; 42: 17
• 10a Chang M.-Y, Tsai M.-C, Lin C.-Y. RSC Adv. 2021; 11: 11655
• 10b Kshatriya R, Jejurkar VP, Saha S. Tetrahedron 2018; 74: 811
• 10c Santos CM. M, Silva AM. S. Eur. J. Org. Chem. 2017; 3115
• 11a Vimal M, Pathak U, Halve AK. Synth. Commun. 2019; 49: 2805
• 11b Liu R, Zhang Y, Xu K, Tan G. Synth. Commun. 2017; 47: 1
• 12a McGarry LW, Detty MR. J. Org. Chem. 1990; 55: 4349
• 12b Nakatani K, Okamoto A, Saito I. Tetrahedron 1996; 52: 9421
• 12c Yoshida M, Fujino Y, Doi T. Org. Lett. 2011; 13: 4526
• 13a Zhao J, Zhao Y, Fu H. Org. Lett. 2012; 14: 2710
• 13b Zhao J, Zhao Y, Fu H. Angew. Chem. Int. Ed. 2011; 50: 3769
• 14a Sun D.-W, Zhou Y.-Y, Jiang M, Nian T, Liu J.-T. Tetrahedron 2021; 91: 132226
• 14b Son SH, Jang HJ, Cho YY, Kim DH, Yoo H.-S, Shin J.-W, Lee SJ, Kim YM, Kim N.-J. RSC Adv. 2021; 11: 14000
• 14c Godoi B, Sperança A, Menezes PH, Bruning CA, Nogueira CW, Back DF, Zeni G. Adv. Synth. Catal. 2011; 353: 2042
• 14d Zhou C, Dubrovsky AV, Larock RC. J. Org. Chem. 2006; 71: 1626
• 15a Patil AM, Kamble DA, Lokhande PD. Synth. Commun. 2018; 48: 1299
• 15b Gobbi S, Rampa A, Bisi A, Belluti F, Piazzi L, Valent P, Caputo A, Zampiron A, Carrara M. J. Med. Chem. 2003; 46: 3662
• 15c de la Torre MD. L, Marcorin GL, Pirri G, Tome AC, Silva AM. S, Cavaleira JA. S. Tetrahedron Lett. 2002; 43: 1689
• 16 Chakraborti AK, Sharma L, Nayak MK. J. Org. Chem. 2002; 67: 6406
• 17 Chow ST, Ng TL. Water Res. 1983; 17: 117
• 18 Nayak MK, Chakraborti AK. Tetrahedron Lett. 1997; 38: 8749