Selective Preparation of Xanthones from 2-Bromofluorobenzenes and Salicylaldehydes via Palladium-Catalyzed Acylation–S_NAr Approach

Abstract

A regioselective pathway for the preparation of xanthones from 2-bromofluorobenzenes and salicylaldehydes has been developed. The reaction proceeded through palladium-catalyzed acylation–S_NAr sequence. Good to moderate yields of the desired xanthones were prepared in one step. Based on the results of control experiments, a possible reaction mechanism has been proposed.

Key words

xanthone - palladium catalyst - coupling - heterocycle synthesis - acylation - nucleophilic substitution

• References and Notes

• 1a Roberts JC. Chem. Rev. 1961; 61: 591
• 1b Masters K.-S, Bräse S. Chem. Rev. 2012; 112: 3717
• 2 Lesch B, Bräse S. Angew. Chem. Int. Ed. 2004; 43: 115
• 3a Steiner LF, Summerland SA. J. Econ. Entomol. 1943; 36: 435
• 3b Engel MG, Engel FL. J. Biol. Chem. 1947; 167: 535
• 3c Obot IB, Obi-Egbedib NO. Curr. Appl. Phys. 2011; 11: 382

For selected recent examples, see:
• 4a Palmer BD, Henare K, Woon S.-T, Sutherland R, Reddy C, Wang L.-CS, Kieda C, Ching L.-M. J. Med. Chem. 2007; 50: 3757
• 4b Omolo JJ, Johnson MM, van Vuuren SF, de Koning CB. Bioorg. Med. Chem. Lett. 2011; 21: 7085
• 4c Guo N, Liu J, Qin L, Jiang D, You X, Lu K, Teng Y.-O, Yu P. J. Asian Nat. Prod. Res. 2015; 17: 377
• 5 Sousa E, Pinto MM. Curr. Med. Chem. 2005; 12: 2447
• 6 Holleman AF. Org. Synth. 1927; 7: 84

For some recent representative synthetic pathways of xanthones, see:
• 7a Zhao J, Larock RC. Org. Lett. 2005; 7: 4273
• 7b Zhao J, Larock RC. J. Org. Chem. 2007; 72: 583
• 7c Wertz S, Leifert D, Studer A. Org. Lett. 2013; 15: 928
• 7d Yang J, Dong C, Li H, Li H, Li Y. Chin. Sci. Bull. 2012; 57: 2364
• 7e Wang P, Rao H, Hua R, Li C.-J. Org. Lett. 2012; 14: 902
• 7f Manna SK, Lavanya S, Manda K, Panda G. Tetrahedron Lett. 2014; 55: 5759
• 7g Zhang H, Shi R, Gan P, Liu C, Ding A, Wang Q, Lei A. Angew. Chem. Int. Ed. 2012; 51: 5204
• 7h Xu Y, Zhou J, Zhang C, Chen K, Zhang T, Du Z. Tetrahedron Lett. 2014; 55: 6432
• 7i Genovese S, Fiorito S, Specchiulli MC, Taddeo VA, Epifano F. Tetrahedron Lett. 2015; 56: 847
• 7j Hu J, Adogla EA, Ju Y, Fan D, Wang Q. Chem. Commun. 2012; 48: 11256
• 7k Menéndez CA, Nador F, Radivoy G, Gerbino DC. Org. Lett. 2014; 16: 2846
• 7l Wang S, Xie K, Tan Z, An X, Zhou X, Guo C.-C, Peng Z. Chem. Commun. 2009; 6469
• 7m Rao H, Ma X, Liu Q, Li Z, Cao S, Li C.-J. Adv. Synth. Catal. 2013; 355: 2191
• 7n Suzuki Y, Fukuta Y, Ota S, Kamiya M, Sato M. J. Org. Chem. 2011; 76: 3960
• 7o Jiang N, Li S.-Y, Xie S.-S, Yao H, Sun H, Wang X.-B, Kong L.-Y. RSC Adv. 2014; 4: 63632
• 7p Barbero N, SanMartin R, Domínguez E. Green Chem. 2009; 11: 830
• 7q Hintermann L, Masuo R, Suzuki K. Org. Lett. 2008; 10: 4859
• 7r Woydziak ZR, Fu L, Peterson BR. J. Org. Chem. 2012; 77: 473
• 7s Johnson MM, Naidoo JM, Fernandes MA, Mmutlane EM, van Otterlo WA. L, de Koning CB. J. Org. Chem. 2010; 75: 8701
• 8a Satoh T, Itaya T, Miura M, Nomura M. Chem. Lett. 1996; 823
• 8b Álvarez-Bercedo P, Flores-Gaspar A, Correa A, Martin R. J. Am. Chem. Soc. 2010; 132: 466
• 8c Solé D, Mariani F. J. Org. Chem. 2013; 78: 8136
• 8d Nowrouzi N, Motevalli S, Tarokh D. J. Mol. Catal. A: Chem. 2015; 396: 224
• 8e Solé D, Mariani F, Fernández I. Eur. J. Org. Chem. 2015; 3935
• 9 General Procedure for the Synthesis of Xanthone To an oven-dried 25 mL Schlenk tube containing a stirring bar was added Pd(OAc)₂ (4.5 mg, 0.02 mmol), n-BuPAd₂ (15.7 mg, 0.44 mmol), 2-bromofluorobenzene (0.50 mmol), salicylaldehyde (0.50 mmol), K₂CO₃ (1.0 mmol). The Schlenk tube was vacuumed and then purged with argon before DMF (2.0 mL) was injected using a syringe. Afterwards the Schlenk tube in the ice bath was degassed by evacuation and backfilling with argon three times. The reaction mixture was then stirred for 12 h at 120 °C. After the reaction was complete, the reaction mixture was diluted with H₂O (5 mL), extracted with EtOAc (3 × 10 mL) and dried with anhydrous Na₂SO₄. After filtration and addition of silica gel into the solution, the organic solvent was reduced evaporated. The crude product was purified by column chromatography using EtOAc–n-pentane. Xanthenone (3a) White solid; yield: 74.5 mg (76%). ¹H NMR (300 MHz, CDCl₃): δ = 8.35 (2 H, ddd, J = 8.0, 1.7, 0.5 Hz), 7.73 (2 H, ddd, J = 8.7, 7.1, 1.8 Hz), 7.52–7.48 (2 H, m), 7.38 (2 H, ddd, J = 8.1, 7.1, 1.1 Hz). ¹³C NMR (75 MHz, CDCl₃): δ = 177.27, 156.20, 134.86, 126.77, 123.94, 121.88, 118.02. GC–MS (EI, 70 eV): m/z (%) = 196 (100), 168 (75), 139 (58), 113 (6), 92 (8), 74 (11), 63 (20). HRMS (EI): m/z calcd for C₁₃H₈O₂ [M]⁺: 196.05188; found: 196.05185.
• 10a Wang L, Lu W. Org. Lett. 2009; 11: 1079
• 10b Li C.-L, Qi X, Wu X.-F. J. Mol. Catal. A: Chem. 2015; 406: 94
• 11a Stephan MS, Teunissen AJ. J. M, Verzijl GK. M, de Vries JG. Angew. Chem. Int. Ed. 1998; 37: 662
• 11b Jutand A, Négri S, de Vries JG. Eur. J. Inorg. Chem. 2002; 1711
• 12 Ackerman LK. G, Lovell MM, Weix DJ. Nature 2015; 524: 454