Facile Protocols towards C2-Arylated Benzoxazoles using Fe(III)-Catalyzed C(sp ²-H) Functionalization and Metal-Free Domino Approach

Abstract

Considering their growing attention in the field of medicinal chemistry and drug-discovery research, the facile and convenient approaches towards the preparation of 2-aryl benzoxazole derivatives have been described. The transformation is accomplished by using Fe(III)-catalyzed C–H activation of benzoxazoles with boronic acids to obtain a wide range of C2-arylated benzoxazoles in high yields. The developed method excludes the formation of self-coupling compounds as side products. On the other hand, the synthesis of the products is also achieved via a metal-free domino protocol by the reaction between 1-nitroso-2-naphthol and acetophenones using catalytic amounts of CBr₄ in the presence of Cs₂CO₃ as base. The devised tandem method avoids the use of pre-activated α-haloketones as substrates. Due to their immense impact in marketed drugs and molecules under clinical trial, the described method can be a powerful tool for their synthesis which ­restricts the use of precious metals as catalyst.

Key words

benzoxazoles - Fe(III)-catalysis - C-arylation - C–H Activation - domino reaction

• References and Notes

• 1a Demmer CS. Bunch L. Eur. J. Med. Chem. 2015; 97: 778
• 1b Gautam MK. Sonal; Sharma NK. Priyanka; Jha KK. Int. J. Chem. Tech. Res. 2012; 4: 640
• 1c Hartner FW. Jr. Oxazoles: In Comprehensive Heterocyclic Chemistry II. Vol. 3. Katritzky AR. Rees CW. Scriven EF. V. Pergamon Press; Oxford, UK: 1996: 261-318
• 1d Johnson SM. Connelly S. Wilson IA. Kelly JW. J. Med. Chem. 2008; 51: 260
• 1e Razavi H. Palaninathan SK. Powers ET. Wiseman RL. Purkey HE. Mohamedmohaideen NN. Deechongkit S. Chiang KP. Dendle MT. A. Sacchettini JC. Kelly JW. Angew. Chem. Int. Ed. 2003; 42: 2758
• 1f Kumar RV. Asian J. Chem. 2004; 16: 1241
• 1g Boyd GV. In Science of Synthesis: Houben-Weyl Methods of Molecular Transformations . Vol. 11. Schaumann E. Thieme; Stuttgart: 2002: 481
• 1h Doepp H. Doepp D. In Houben-Weyl Methoden der Organischen Chemie . Vol. E8a. Schaumann E. Thieme; Stuttgart: 1993: 1020
• 2a Jin Z. Nat. Prod. Rep. 2011; 28: 1143
• 2b Yeh VS. C. Tetrahedron 2004; 60: 11995
• 2c Rodríguezam Reodrgueonlez E. Org. Lett. 1999; 3: 527
• 2d Ueki M. Ueno K. Miyadoh S. Abe K. Shibata K. Taniguchi M. Oi S. J. Antibiot. 1993; 46: 1089
• 2e Sato S. Kajiura T. Noguchi M. Takehana K. Kobayashi T. Tsuji T. J. Antibiot. 2001; 54: 102
• 2f Lin F.-W. Damu AG. Wu T.-S. J. Nat. Prod. 2006; 69: 93
• 2g Don M.-J. Shen C.-C. Lin Y.-L. Syu W.-J. Ding Y.-H. Sun C.-M. J. Nat. Prod. 2005; 68: 1066
• 3a Tully DC. Liu H. Alper PB. Chatterjee AK. Epple R. Roberts MJ. Williams JA. Nguyen KT. Woodmansee DH. Tumanut C. Li J. Spraggon G. Chang J. Tuntland T. Harris JL. Karanewsky DS. Bioorg. Med. Chem. Lett. 2006; 16: 1975
• 3b McGrath ME. Sprengeler PA. Hill CM. Martichonok V. Cheung H. Somoza JR. Palmer JT. Janc JW. Biochemistry 2003; 42: 15018
• 3c Reynolds MB. DeLuca MR. Kerwin SM. Bioorg. Chem. 1999; 27: 326
• 3d Kumar A. Ahmad P. Maurya RA. Singh AB. Srivastava AK. Eur. J. Med. Chem. 2009; 44: 109
• 3e Gong B. Hong F. Kohm C. Bonham L. Klein P. Bioorg. Med. Chem. Lett. 2004; 14: 1455
• 3f Yoshida S. Shiokawa S. Kawano K. Ito T. Murakami H. Suzuki H. Sato Y. J. Med. Chem. 2005; 48: 7075
• 3g Sato Y. Yamada M. Yoshida S. Soneda T. Ishikawa M. Nizato T. Suzuki K. Konno F. J. Med. Chem. 1998; 41: 3015
• 3h Leventhal L. Brandt MR. Cummons TA. Piesla MJ. Rogers KE. Harris HA. Eur. J. Pharmacol. 2006; 553: 146
• 3i Manas ES. Unwalla RJ. Xu ZB. Malamas MS. Miller CP. Harris HA. Hsiao C. Akopian T. Hum W.-T. Malakian K. Wolfrom S. Bapat A. Bhat RA. Stahl ML. Somers WS. Alvarez JC. J. Am. Chem. Soc. 2004; 126: 15106
• 3j Malamas MS. Manas ES. McDevitt RE. Gunawan I. Xu ZB. Collini MD. Miller CP. Dinh T. Henderson RA. Keith JC. Jr. Harris HA. J. Med. Chem. 2004; 47: 5021
• 3k Sun L.-Q. Chen J. Bruce M. Deskus JA. Epperson JR. Takaki K. Johnson G. Iben L. Mahle CD. Ryan E. Xu C. Bioorg. Med. Chem. Lett. 2004; 14: 3799
• 4a Ooyama Y. Kagawa Y. Fukuoka H. Ito G. Harima Y. Eur. J. Org. Chem. 2009; 5321
• 4b Ooyama Y. Egawa H. Yoshida K. Eur. J. Org. Chem. 2008; 5239
• 4c Ooyama Y. Kagawa Y. Harima Y. Eur. J. Org. Chem. 2007; 3613
• 4d Ohshima A. Momotake A. Nagahata R. Arai T. J. Phys. Chem. A 2005; 109: 9731
• 4e Mayer Dumas Cheresse F. Chem. Commun. 2005; 345
• 4f Taki M. Wolford JL. O’Halloran TV. J. Am. Chem. Soc. 2004; 126: 712
• 4g Seo J. Kim S. Park SY. J. Am. Chem. Soc. 2004; 126: 11154
• 5 Wu X.-F. Anbarasan P. Neumann H. Beller M. Angew. Chem. Int. Ed. 2010; 49: 7316
• 6a Boger DL. Miyauchi H. Hedrick MP. Bioorg. Med. Chem. Lett. 2001; 11: 1517
• 6b Boger DL. Sato H. Lerner AE. Hedrick MP. Fecik RA. Miyauchi H. Wilkie GD. Austin BJ. Patricelli MP. Cravatt BF. Proc. Natl. Acad. Sci. U. S. A. 2000; 97: 5044
• 6c Chen J. Li C.-M. Wang J. Ahn S. Wang Z. Lu Y. Dalton JT. Miller DD. Li W. Bioorg. Med. Chem. 2011; 19: 4782
• 6d Harn NK. Gramer CJ. Anderson BA. Tetrahedron Lett. 1995; 36: 9453
• 7a Sharma S. Khan IA. Saxena AK. Adv. Synth. Catal. 2013; 355: 673
• 7b Yang K. Zhang C. Wang P. Zhang Y. Ge H. Chem.-Eur. J. 2014; 20: 7241
• 8a Richardson C. Rewcastle GW. Hoyer D. Denny WA. J. Org. Chem. 2005; 70: 7436
• 8b Reeder MR. Gleaves HE. Hoover SA. Imbordino RJ. Pangborn JJ. Org. Process Res. Dev. 2003; 7: 696
• 8c Liebeskind LS. Srogl J. Org. Lett. 2002; 6: 979
• 8d Anderson BA. Harn NK. Synthesis 1996; 583
• 8e Kosugi M. Koshiba M. Atoh A. Sano H. Migita T. Bull. Chem. Soc. Jpn. 1986; 59: 677
• 8f Ackermann L. Althammer A. Fenner S. Angew. Chem. Int. Ed. 2009; 48: 201
• 8g Roger J. Doucet H. Org. Biomol. Chem. 2008; 6: 169
• 8h Yoshizumi T. Tsurugi H. Satoh T. Miura M. Tetrahedron Lett. 2008; 49: 1598
• 8i Do HQ. Daugulis O. J. Am. Chem. Soc. 2007; 129: 12404
• 9a Barbero N. Carril M. SanMartin R. Domínguez E. Tetrahedron 2007; 63: 10425
• 9b Evindar G. Batey RA. J. Org. Chem. 2006; 71: 1802
• 9c Ueda S. Nagasawa H. Angew. Chem. Int. Ed. 2008; 47: 6411
• 9d Viirre RD. Evindar G. Batey RA. J. Org. Chem. 2008; 73: 3452
• 9e Altenhoff G. Glorius F. Adv. Synth. Catal. 2004; 346: 1661
• 9f Saha P. Ramana T. Purkait N. Ali MA. Paul R. Punniyamurthy T. J. Org. Chem. 2009; 74: 8719
• 9g Yang D. Zhu X. Wei W. Jiang M. Zhang N. Ren D. You J. Wang H. Synlett 2014; 25: 729
• 9h Bose DS. Idrees M. Synthesis 2010; 398
• 10a Fan X. He Y. Zhang X. Guo S. Wang Y. Tetrahedron 2011; 67: 6369
• 10b Cui L. He Y. Fan X. Chin. J. Chem. 2012; 30: 992
• 10c Seijas JV. Zquez-Tato MP. Carballido-Reboredo MR. Crecente-Campo J. Synlett 2007; 313
• 10d Isomura Y. Ito N. Homma H. Abe T. Kubo K. Chem. Pharm. Bull. 1983; 31: 3168
• 10e Terashima M. Ishii M. Synthesis 1982; 484
• 10f Hegedus LS. Odle RR. Winton PM. Weider PR. J. Org. Chem. 1982; 47: 2607
• 10g Holan G. Evans JJ. Linton M. J. Chem. Soc., Perkin Trans. 1 1977; 1200
• 10h Jackson PF. Morgan KJ. Turner AM. J. Chem. Soc., Perkin Trans. 2 1972; 1582
• 10i Kanaoka Y. Hamada T. Yonemitsu O. Chem. Pharm. Bull. 1970; 18: 587
• 10j Hein DW. Alheim RJ. Leavitt JJ. J. Am. Chem. Soc. 1957; 79: 427
• 10k Bywater WG. Coleman WR. Kamm O. Merrit HH. J. Am. Chem. Soc. 1945; 67: 905
• 10l Reddy MB. M. Nizam A. Pasha MA. Synth. Commun. 2011; 41: 1838
• 10m Li H. Wei K. Wu Y.-J. Chin.J. Chem. 2007; 25: 1704
• 10n Osma A.-M. Bassiouni I. J. Org. Chem. 1962; 27: 558
• 10o Stephens FF. Nature (London) 1949; 164: 243
• 11a Kumar RV. Asian J. Chem. 2004; 16: 1241
• 11b Aljaar N. Malakar CC. Conrad J. Frey W. Beifuss U. J. Org. Chem. 2013; 78: 154
• 11c Aljaar N. Malakar CC. Conrad J. Beifuss U. J. Org. Chem. 2015; 80: 10829
• 12 Correa A. Fiser B. Gómez-Bengoa E. Chem. Commun. 2015; 51: 13365
• 13 Muto K. Yamaguchi J. Itami K. J. Am. Chem. Soc. 2012; 134: 169
• 14 Wang J. Hou J.-T. Wen J. Zhang J. Yu X.-Q. Chem. Commun. 2011; 47: 3652
• 15 Wen J. Qin S. Ma L.-F. Dong L. Zhang J. Liu S.-S. Duan Y.-S. Chen S.-Y. Hu C.-W. Yu X.-Q. Org. Lett. 2010; 12: 2694
• 16a Hachiya H. Hirano K. Satoh T. Miura M. ChemCatChem. 2010; 2: 1403
• 16b Hachiya H. Hirano K. Satoh T. Miura M. Org. Lett. 2009; 11: 1737
• 16c Canivet J. Yamaguchi J. Ban I. Itami K. Org. Lett. 2009; 11: 1733
• 16d Shen X.-B. Zhang Y. Chen W.-X. Xiao Z.-K. Hu T.-T. Shao LX. Org. Lett. 2014; 16: 1984
• 16e Boissarie PJ. Hamilton ZE. Lang S. Murphy JA. Suckling CJ. Org. Lett. 2011; 13: 6184
• 16f Guru MM. Ali MA. Punniyamurthy T. Org. Lett. 2011; 13: 1194
• 17 Do H.-Q. Daugulis O. J. Am. Chem. Soc. 2007; 129: 12404

For recent reviews, see:
• 18a Gensch T. Hopkinson MN. Glorius F. Wencel-Delord J. Chem. Soc. Rev. 2016; 45: 2900
• 18b Davies HM. L. Morton D. J. Org. Chem. 2016; 81: 343
• 18c Kazzouli SE. Koubachi J. Brahmi NE. Guillaumet G. RSC Adv. 2015; 5: 15292
• 18d Ackermann L. Vicente R. Kapdi AR. Angew. Chem. Int. Ed. 2009; 48: 9792
• 19a Xu H. Wu X. Ding Y. Peng C. Peng X. Asian J. Chem. 2015; 27: 3185
• 19b Das B. Venkateswarlu K. Mahender G. Mahender I. Tetrahedron Lett. 2005; 46: 3041
• 20a Ilies L. Matsumoto A. Kobayashi M. Yoshikai N. Nakamura E. Synlett 2012; 23: 2381
• 20b Adak L. Yoshikai N. Tetrahedron 2012; 68: 5167
• 20c Wong MY. Yamakawa T. Yoshikai N. Org. Lett. 2015; 17: 442
• 20d Matsubara T. Ilies L. Nakamura E. Chem. -Asian J. 2016; 11: 380
• 20e Shang R. Ilies L. Nakamura E. Chem. Rev. 2017; 117: 9086
• 21 General Experimental Procedure for the Synthesis of Products 3a–v: Method A: A-10 mL pressure tube was charged with a mixture of 1a–f (1.0 mmol), 2a–o (1.0 mmol), FeCl₃ (0.05 mmol, 8.1 mg), 1,10-phenanthroline (0.1 mmol, 18 mg), DCIB (1.3 mmol, 165 mg), Cs₂CO₃ (1.5 mmol 487 mg), and DMF (2 mL). The pressure tube was then sealed and heated at 100 °C for 16 h. After completion of the reaction, the mixture was diluted with hot EtOAc (50 mL) and H₂O (100 mL) and extracted with EtOAc (3 × 50 mL). The combined organic layer was washed with brine (2 × 50 mL) and dried over anhyd Na₂SO₄. The solvent was removed under reduced pressure and the remaining residue was purified by flash chromatography over silica gel using hexane–EtOAc (10:1) as an eluent to obtain the desired products 3a–v. Method B: In an oven-dried 100-mL round-bottomed flask 4a–b (1.0 mmol), 5a–k (1.0 mmol), CBr₄(0.5 mmol, 165 mg), Cs₂CO₃ (2.1 mmol, 682 mg) and 10 mL MeCN (10 mL) were added successively and the reaction mixture was heated for 6 h at 80 °C under nitrogen atmosphere. The reaction mixture was allowed to cool to r.t. and then the solvent was removed under vacuum. The crude product was purified by using column chromatography over silica gel using hexane–EtOAc (10:1) as an eluent to get the products 3a–f, 3h, 3i, 3k, 3m, 3w, 3x as yellow crystalline solids.
• 22 Characterization Data for 2-Phenylnaptho[1,2-d]oxazole (3a): yield: 85%, 208 mg (Method A) and 69%, 169 mg (Method B). ¹H NMR (400 MHz, CDCl₃): δ = 7.45–7.49 (m, 5 H, 8-H, 9-H, 10-H, 11-H, 12-H), 7.69 [dd, ³ J (1-H, 2-H) = 7.0 Hz, ³ J (2-H, 3-H) = 8.0 Hz, ³ J (3-H, 4-H) = 8.1 Hz, ³ J (2-H, 3-H), 2 H, 2-H, 3-H], 7.89 [d, ³ J (3-H, 4-H) = 7.0 Hz, 1 H, 4-H], 8.23–8.29 [m, ³ J (5-H, 6-H)= 8.9 Hz, 2 H, 5-H, 6-H], 8.52 [d, ³ J (1-H, 2-H) = 8.0 Hz, 1 H, 1-H]. ¹³C NMR (100 MHz, CDCl₃): δ = 109.8 (C-6), 115.5 (C-14), 121.2 (C-1), 123.4 (C-15), 124.3 (C-2), 124.9 (C-3), 125.9 (C-4), 126.2 (C-8, C-12), 127.5 (C-10), 127.8 (C-9, C-11), 130.0 (C-5), 130.1 (C-19), 136.5(C-16), 147.0 (C-17), 161.2 (C-18). HRMS (EI): m/z [M + H]⁺ calcd for C₁₇H₁₂NO: 246.0918; found: 246.0914.