Synthesis of Benzotriazepine Derivatives via [4+3] Cycloaddition of Aza-o-quinone Methide Intermediates and Azomethine Imines

Abstract

An efficient and unprecedented [4+3] cycloaddition between in situ generated aza-o-quinone methides and azomethine imines via an aza-Michael/aminalization sequence has been developed. The scalable protocol allows to expeditiously assemble a valuable heterocyclic system incorporating tetrahydroisoquinoline and benzotriazepine scaffolds in good to excellent yields under mild conditions.

Key words

[4+3] cycloaddition - aza-o-quinone methide - azomethine imine - triazepine - 7-membered heterocycles

• References

• 1 Quinone Methides. Rokita SE. John Wiley & Sons; New York: 2009

For reviews on o-quinone methides, see:
• 2a Willis NJ, Bray CD. Chem. Eur. J. 2012; 18: 9160
• 2b Singh MS, Nagaraju A, Anand N, Chowdhury S. RSC Adv. 2014; 4: 55924
• 2c Caruana L, Fochi M, Bernardi L. Molecules 2015; 20: 11733
• 2d Wang Z, Sun J. Synthesis in press; DOI:
• 3 Bai W.-J, David JG, Feng Z.-G, Weaver MG, Wu K.-L, Pettus TR. R. Acc. Chem. Res. 2014; 47: 3655
• 4a Burgess EM, McCullagh L. J. Am. Chem. Soc. 1966; 88: 1580
• 4b Ikeda M, Matsugashita S, Tabusa F, Ishibashi H, Tamura Y. J. Chem. Soc., Chem. Commun. 1975; 575
• 4c Lancaster M, Smith DJ. H. J. Chem. Soc., Chem. Commun. 1980; 471
• 5a Bowen RD, Davies DE, Fishwick CW. G, Glasbey TO, Noyce SJ, Storr RC. Tetrahedron Lett. 1982; 23: 4501
• 5b Wojciechowski K. Tetrahedron 1993; 49: 7277
• 5c Wiebe JM, Caillé AS, Trimble L, Lau CK. Tetrahedron 1996; 52: 11705
• 5d Nishiyama K, Kubo H, Sato T, Higashiyama K, Ohmiya S. Heterocycles 1998; 6: 1103
• 6 Ito Y, Miyata S, Nakatsuka M, Saegusa T. J. Am. Chem. Soc. 1981; 103: 5250
• 7a Steinhagen H, Corey EJ. Angew. Chem. Int. Ed. 1999; 38: 1928
• 7b Avemaria F, Vanderheiden S, Bräse S. Tetrahedron 2003; 59: 6785
• 7c May JA, Zeidan RK, Stoltz BM. Tetrahedron Lett. 2003; 44: 1203
• 7d Yang Q.-Q, Xiao C, Lu L.-Q, An J, Tan F, Li B.-J, Xiao W.-J. Angew. Chem. Int. Ed. 2012; 51: 9137
• 7e Huang H, Yang Y, Zhang X, Zeng W, Liang Y. Tetrahedron Lett. 2013; 54: 6049
• 7f Yang Q.-Q, Wang Q, An J, Chen J.-R, Lu L.-Q, Xiao W.-J. Chem. Eur. J. 2013; 19: 8401
• 7g Hovey MT, Check CT, Sipher AF, Scheidt KA. Angew. Chem. Int. Ed. 2014; 53: 9603
• 7h Lee A, Younai A, Price CK, Izquierdo J, Mishra RK, Scheidt KA. J. Am. Chem. Soc. 2014; 136: 10589

For an excellent review, see:
• 8a Nájera C, Sansano JM, Yus M. Org. Biomol. Chem. 2015; 13: 8596

For selected examples, see:
• 8b Truce WE, Allison JR. J. Org. Chem. 1975; 40: 2260
• 8c Hashimoto T, Maeda Y, Omote M, Nakatsu H, Maruoka K. J. Am. Chem. Soc. 2010; 132: 4076
• 8d Hashimoto T, Omote M, Maruoka K. Angew. Chem. Int. Ed. 2011; 50: 3489
• 8e Hu X.-Q, Chen J.-R, Gao S, Feng B, Lu L.-Q, Xiao W.-J. Chem. Commun. 2013; 49: 7905
• 8f Wang D, Deng H.-P, Wei Y, Xu Q, Shi M. Eur. J. Org. Chem. 2013; 2013, 401
• 8g Zhou Y.-Y, Li J, Ling L, Liao S.-H, Sun X.-L, Li Y.-X, Wang L.-J, Tang Y. Angew. Chem. Int. Ed. 2013; 52: 1452
• 8h Li W, Jia Q, Du Z, Zhang K, Wang J. Chem. Eur. J. 2014; 20: 4559
• 8i Gao Z.-H, Chen X.-Y, Cheng J.-T, Liao W.-L, Ye S. Chem. Commun. 2015; 51: 9328
• 8j Hesping L, Biswas A, Daniliuc CG, Mück-Lichtenfeld C, Studer A. Chem. Sci. 2015; 6: 1252
• 8k Zhang L, Liu H, Qiao G, Hou Z, Liu Y, Xiao Y, Guo H. J. Am. Chem. Soc. 2015; 137: 4316
• 9a Bunin BA, Plunkett MJ, Ellman JA. Proc. Natl. Acad. Sci. U.S.A. 1994; 91: 4708
• 9b Martín-Martínez M, Bartolomé-Nebreda JM, Gómez-Monterrey I, González-Muñiz R, García-López MT, Ballaz S, Barber A, Fortuño A, Del Río J, Herranz R. J. Med. Chem. 1997; 40: 3402
• 9c Boitano A, Ellman JA, Glick GD, Opipari AW. J. Cancer Res. 2003; 63: 6870
• 9d Welsch ME, Snyder SA, Stockwell BR. Curr. Opin. Chem. Biol. 2010; 14: 347
• 10a Fernández P, Guillén MI, Ubeda A, López-Cremades P, Aller E, Lorenzo A, Molina P, Alcaraz MJ. Naunyn-Schmiedeberg’s Arch. Pharmacol. 2003; 368: 26
• 10b McDonald IM, Austin C, Buck IM, Dunstone DJ, Griffin E, Harper EA, Hull RA. D, Kalindjian SB, Linney ID, Low CM. R, Pether MJ, Spencer J, Wright PT, Adatia T, Bashall A. J. Med. Chem. 2006; 49: 2253
• 10c McDonald IM, Black JW, Buck IM, Dunstone DJ, Griffin EP, Harper EA, Hull RA. D, Kalindjian SB, Lilley EJ, Linney ID, Pether MJ, Roberts SP, Shaxted ME, Spencer J, Steel KI. M, Sykes DA, Walker MK, Watt GF, Wright L, Wright PT, Xun W. J. Med. Chem. 2007; 50: 3101
• 11a Schneider CS, Weber KH, Daniel H, Bechtel WD, Boeke-Kuhn K. J. Med. Chem. 1984; 27: 1150
• 11b Bringmann G, Rübenacker M, Geuder T, Aké-Assi L. Phytochemistry 1991; 30: 3845
• 11c Scott JD, Williams RM. Chem. Rev. 2002; 102: 1669
• 12 After submission, we became aware of a parallel independent work: Chen L, Yang GM, Wang J, Jia QF, Wei J, Du ZY. RSC Adv. 2015; 5: 76696