Palladium-Catalyzed, Microwave-Assisted Synthesis of 3,4-Dihydro-3-oxo-2H-1,4-benzoxazines: An Improved Catalytic System and Multicomponent Process

Abstract

An improved palladium-catalyzed system is established for the synthesis of 3,4-dihydro-3-oxo-2H-1,4-benzoxazines from less reactive ethyl 2-(2-chlorophenoxy)alkanoates and aryl amines under controlled microwave heating, employing 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (XPhos) as the ligand. Moreover, a high-yielding, three-component reaction protocol is disclosed for the efficient one-pot synthesis of 3,4-dihydro-3-oxo-2H-1,4-benzoxazines from 2-halophenols, ethyl 2-bromoalkanoates, and aryl amines. Microwave heating at high temperature is necessary to achieve high yields with 2-chlorophenol. A wide range of substrates is tolerated affording the desired products in good to excellent yields.

Key words

multicomponent reactions - microwave irradiation - palladium­-catalyzed - 3,4-dihydro-3-oxo-2H-1,4-benzoxazines - cascade process

• References

• 1a Wilson RM, Danishefsky SJ. J. Org. Chem. 2006; 71: 8329
• 1b Koch MA, Waldmann H. Drug Discovery Today 2005; 10: 471
• 1c Hubel K, Lessmann T, Waldmann H. Chem. Soc. Rev. 2008; 37: 1361
• 1d Burke MD, Berger EM, Schreiber SL. Science 2003; 302: 613
• 1e Spring DR. Org. Biomol. Chem. 2003; 1: 3867
• 1f Burke MD, Lalic G. Chem. Biol. 2002; 9: 535
• 1g Schreiber SL. Science 2000; 287: 1964
• 2a Feng BY, Simeonov A, Jadhav A, Babaoglu K, Inglese J, Shoichet BK, Austin CP. J. Med. Chem. 2007; 50: 2385
• 2b Ferreira RS, Simeonov A, Jadhav A, Eidam O, Mott BT, Keiser MJ, McKerrow JH, Maloney DJ, Irwin JJ, Shoichet BK. J. Med. Chem. 2010; 53: 4891
• 2c Phelan RM, DiPardo BJ, Townsend CA. ACS Chem. Biol. 2012; 7: 835
• 2d Kim W, Kim Y, Min J, Kim DJ, Chang Y.-T, Hecht MH. ACS Chem. Biol. 2006; 1: 461
• 3a Li M, Lv X.-L, Wen L.-R, Hu Z.-Q. Org. Lett. 2013; 15: 1262
• 3b Huang Y, Khoury K, Chanas T, Dömling A. Org. Lett. 2012; 14: 5916
• 3c Dömling A, Wang W, Wang K. Chem. Rev. 2012; 112: 3083
• 3d Ruijter E, Scheffelaar R, Orru R. Angew. Chem. Int. Ed. 2011; 28: 6234
• 3e Hulme C, Dietrich J. Mol. Diversity 2009; 13: 195
• 3f Armstrong RW, Combs AP, Tempest PA, Brown SD, Keating TA. Acc. Chem. Res. 1996; 29: 123
• 3g Ganem B. Acc. Chem. Res. 2009; 42: 46
• 3h Heijden G, Ruijter E, Orru RV. A. Synlett 2013; 24: 666
• 3i Shestopalov AM, Shestopalov AA, Rodinovskaya LA. Synthesis 2008; 1
• 4a Dallinger D, Kappe CO. Chem. Rev. 2007; 107: 2563
• 4b Yu C.-W, Chen GS, Huang C.-W, Chern J.-W. Org. Lett. 2012; 14: 3688
• 4c Nguyen HH, Kurth MJ. Org. Lett. 2013; 15: 362
• 4d Kappe CO. Acc. Chem. Res. 2013; 46 in press; doi: 10.1021/ar300318c
• 4e Loupy A In Microwaves in Organic Synthesis . Wiley-VCH; Weinheim: 2002
• 4f Kappe CO, Pieber B, Dallinger D. Angew. Chem. Int. Ed. 2013; 52: 1088
• 5a Geden JV, Pancholi AK, Shipman M. J. Org. Chem. 2013; 78: 4158
• 5b Yang D, Burugupalli S, Daniel D, Chen Y. J. Org. Chem. 2012; 77: 4466
• 5c Mehta VP, Modha SG, Ruijter E, van Hecke K, van Meervelt L, Pannecouque C, Balzarini J, Orru RV. A, van der Eycken E. J. Org. Chem. 2011; 76: 2828
• 5d Chebanov VA, Muravyova EA, Desenko SM, Musatov VI, Knyazeva IV, Shishkina SV, Shishkin OV, Kappe CO. J. Comb. Chem. 2006; 8: 427
• 6a Sainsbury M. Oxazines, Thiazines and their Benzo Derivatives . In Comprehensive Heterocyclic Chemistry . Vol. 3. Katritzky AR, Rees CW. Pergamon; Oxford: 1984: 995-1038
• 6b Dudley DA, Bunker AM, Chi L, Cody WL, Holland DR, Ignasiak DP, Janiczek-Dolphin N, McClanahan TB, Mertz TE, Narasimhan LS, Rapundalo ST, Trautschold JA, Huis CA. V, Edmunds JJ. J. Med. Chem. 2000; 43: 4063
• 6c Caliendo G, Perissutti E, Santagada V, Fiorino F, Severino B, d’Emmanuele di Villa Bianca R, Lippolis L, Pinto A, Sorrentino R. Bioorg. Med. Chem. 2002; 10: 2663

For recent reviews, see:
• 6d Sebille S, de Tullio P, Boverie S, Antoine MH, Lebrun P, Pirotte B. Curr. Med. Chem. 2004; 11: 1213
• 6e Macias FA, Marin D, Oliveros-Bastidas A, Molinillo JM. G. Nat. Prod. Rep. 2009; 26: 478
• 7a Minami Y, Yoshida K, Azuma R, Saeki M, Otani T. Tetrahedron Lett. 1993; 34: 2637

For designed enediynes, see:
• 7b Dai W.-M. Curr. Med. Chem. 2003; 10: 2265

For recent reviews, see:
• 8a Ilaš J, Anderluh PS, Dolenc MS, Kikelj D. Tetrahedron 2005; 61: 7325
• 8b Achari B, Mandal SB, Dutta PK, Chowdhury K. Synlett 2004; 2449

For selected examples, see:
• 8c Wu J, Nie L, Luo J, Dai W.-M. Synlett 2007; 2728
• 8d Hashimoto Y, Ishizaki T, Shudo K. Tetrahedron 1991; 47: 1837
• 8e Yuan Y, Liu G, Li L, Wang Z, Wang L. J. Comb. Chem. 2007; 9: 158
• 8f Rybczynski PJ, Zeck RE, Combs DW, Turchi I, Burris TP, Xu JZ, Yang M, Demarest KT. Bioorg. Med. Chem. Lett. 2003; 13: 235
• 8g Matsumoto Y, Uchida A, Nakahara H, Yanagisawa I, Shibanuma T, Nohira H. Chem. Pharm. Bull. 2000; 48: 428
• 8h Zuo H, Meng L, Ghate M, Hwang K.-H, Cho YK, Chandrasekhar S, Reddy CR, Shi D.-S. Tetrahedron Lett. 2008; 49: 3827
• 9a Caliendo G, Perissutti E, Santagada V, Fiorino F, Severino B, Cirillo D, d’Emmanuele di Villa Bianca R, Lippolis L, Pinto A, Sorrentino R. Eur. J. Med. Chem. 2004; 39: 815
• 9b Dai W.-M, Wang X, Ma C. Tetrahedron 2005; 61: 6879
• 9c Feng G, Wu J, Dai W.-M. Tetrahedron 2006; 62: 4635
• 10a Touzeau F, Arrault A, Guillaumet G, Scalbert E, Pfeiffer B, Rettori M, Renard P, Mérour J.-Y. J. Med. Chem. 2003; 46: 1962
• 10b Arrault A, Touzeau F, Guillaumet G, Léger J.-M, Jarry C, Mérour J.-Y. Tetrahedron 2002; 58: 8145
• 10c Ramesh C, Raju BR, Kavala V, Kuo C.-W, Yao C.-F. Tetrahedron 2011; 67: 1187
• 10d For a solid-phase synthesis, see: Lee CL, Chan KP, Lam Y, Lee SY. Tetrahedron Lett. 2001; 42: 1167
• 11a Feng E, Huang H, Zhou Y, Ye D, Jiang H, Liu H. J. Org. Chem. 2009; 74: 2846
• 11b Chen D, Shen G, Bao W. Org. Biomol. Chem. 2009; 7: 4067
• 11c Yin F, Feng G, Song Q, Qi C. J. Chem. Res. 2012; 41
• 12 Ylijoki KE. O, Kundig EP. Chem. Commun. 2011; 47: 10608
• 13 Banfi L, Basso A, Giardini L, Riva R, Rocca V, Guanti G. Eur. J. Org. Chem. 2011; 100
• 14a Xing X, Wu J, Feng G, Dai W.-M. Tetrahedron 2006; 62: 6774
• 14b Feng G, Wu J, Dai W.-M. Tetrahedron Lett. 2007; 48: 401
• 15 Feng G, Yin F, Chen F, Song Q, Qi C. Synlett 2012; 23, 601