2-Formylpyrroles as Building Blocks in a Divergent Synthesis of Pyrrolizines

Abstract

The selective functionalization of 2-formylpyrrole to provide diverse 1,2- and 1,2,5-substituted pyrroles is described. These compounds were used as versatile building blocks in a divergent synthesis of biologically valuable aza-bycyclic skeletons, such as pyrrolizine and pyrrolizidine derivatives. These bicycles were prepared following metal-free cascade synthetic approaches via regioselective intramolecular 1,3-dipolar cycloadditions and stereoselective Knoevenagel/Michael/ cyclization­ with dimethyl malonate.

Key words

2-formylpyrrole - pyrrolizines - pyrrolizidines - cascade reactions - Knoevenagel/Michael/cyclization

• References

• 1a Meyer SW, Köck M. J. Nat. Prod. 2008; 71: 1524
• 1b Pilli RA, Rosso GB, Ferreira de Oliveira MC. Nat. Prod. Rep. 2010; 27: 1908
• 1c Nisha, Kumar K, Kumar V. RSC Adv. 2015; 5: 10899
• 2a Mantovani SM, Moore BS. J. Am. Chem. Soc. 2013; 135: 18032
• 2b Belal A, El-Gendy BE.-D. M. Bioorg. Med. Chem. 2014; 22: 46
• 3 Robertson J, Stevens K. Nat. Prod. Rep. 2014; 31: 1721
• 4 Meinwald J. J. Nat. Prod. 2011; 74: 305
• 5 Meinwald J. J. Org. Chem. 2009; 74: 1813
• 6 Jin Y.-P, Wei X.-N, Shi Y.-P. Helv. Chim. Acta 2007; 90: 776
• 7 Liu C.-M, Wang H.-X, Wei S.-L, Gao K. Helv. Chim. Acta 2008; 91: 308
• 8 Lu X, Chen G, Hua H, Dai H, Mei W, Xu Y, Pei Y. Fitoterapia 2012; 83: 737
• 9 Majik MS, Tilve SG. Synthesis 2012; 44: 2673
• 10a Park YC, Gunasekera SP, Lopez JV, McCarthy PJ, Wright AE. J. Nat. Prod. 2006; 69: 580
• 10b Kothapalli Y, Puthukanoori RK, Alapati SR. Tetrahedron Lett. 2012; 53: 1891
• 11 Reddy KK. S, Rao BV, Raju SS. Tetrahedron: Asymmetry 2011; 22: 662
• 12a Usuki H, Toyo-oka M, Kanzaki H, Okuda T, Nitoda T. Bioorg. Med. Chem. 2009; 17: 7248
• 12b Zhu J.-S, Nakagawa S, Chen W, Adachi I, Jia Y.-M, Hu X.-G, Fleet GW. J, Wilson FX, Nitoda T, Horne G, van Well R, Kato A, Yu C.-Y. J. Org. Chem. 2013; 78: 10298
• 13a Denmark SE, Herbert B. J. Am. Chem. Soc. 1998; 120: 7357
• 13b Denmark SE, Hurd AR. Org. Lett. 1999; 1: 1311
• 13c Tang M, Pyne SG. J. Org. Chem. 2003; 68: 7818
• 13d Ribes C, Falomir E, Carda M, Alberto Marco J. Org. Lett. 2007; 9: 77
• 13e Ritthiwigrom T, Willis AC, Pyne SG. J. Org. Chem. 2010; 75: 815
• 13f Wardrop DJ, Waidyarachchi SL. Nat. Prod. Rep. 2010; 27: 1431
• 13g Reddy PV, Smith J, Kamath A, Jamet H, Veyron A, Koos P, Philouze C, Greene AE, Delair P. J. Org. Chem. 2013; 78: 4840
• 13h Zheng Z, Tu H, Zhang L. Chem. Eur. J. 2014; 20: 2445
• 13i Mancebo-Aracil J, Nájera C, Castelló LM, Sansano JM, Larrañaga O, de Cózar A, Cossío FP. Tetrahedron 2015; 71: 9645
• 13j Sugimoto K, Yamamoto N, Tominaga D, Matsuya Y. Org. Lett. 2015; 17: 1320
• 14a Baran PS, Richter JM, Lin DW. Angew. Chem. Int. Ed. 2005; 44: 609
• 14b Wang K, Wang Q, Huang R. J. Org. Chem. 2007; 72: 8416
• 14c Trost BM, Dong G. Org. Lett. 2007; 9: 2357
• 14d Bowie AL. Jr, Trauner D. J. Org. Chem. 2009; 74: 1581
• 14e Young IS, Thornton PD, Thompson A. Nat. Prod. Rep. 2010; 27: 1801
• 14f Bae J.-Y, Lee H.-J, Youn S.-H, Kwon S.-H, Cho C.-W. Org. Lett. 2010; 12: 4352
• 14g Bates RW, Sridhar S. J. Org. Chem. 2011; 76: 5026
• 15a Zhu H, Stöckigt J, Yu Y, Zou H. Org. Lett. 2011; 13: 2792
• 15b Kucukdisli M, Opatz T. J. Org. Chem. 2013; 78: 6670
• 15c Kim M, Jung Y, Kim I. J. Org. Chem. 2013; 78: 10395
• 15d Park S, Kim I. Tetrahedron 2015; 71: 1982
• 16a Quiroz-Florentino H, Aguilar R, Santoyo BM, Díaz F, Tamariz J. Synthesis 2008; 1023
• 16b Quiroz-Florentino H, Hernández-Benitez RI, Aviña JA, Burgueño-Tapia E, Tamariz J. Synthesis 2011; 1106
• 17a Tietze LF, Brumby T, Pfeiffer T. Liebigs Ann. Chem. 1988; 9
• 17b Bashiardes G, Safir I, Barbot F. Synlett 2007; 1707
• 17c Albano VG, Gualandi A, Monari M, Savoia D. J. Org. Chem. 2008; 73: 8376
• 18a Barker P, Gendler P, Rapoport H. J. Org. Chem. 1978; 43: 4849
• 18b Tsuchimoto T. Chem. Eur. J. 2011; 17: 4064
• 18c Fleming CL, Ashton TD, Gaur V, McGee SL, Pfeffer FM. J. Med. Chem. 2014; 57: 1132
• 19 Özkan H, Yildirir Y. J. Heterocycl. Chem. 2010; 47: 954
• 20a Arnone A, Broggini G, Passarella D, Terraneo A, Zecchi G. J. Org. Chem. 1998; 63: 9279
• 20b Broggini G, La Rosa C, Pilati T, Terraneo A, Zecchi G. Tetrahedron 2001; 57: 8323
• 21 Marcus J, Brussee J, van der Gen A. Eur. J. Org. Chem. 1998; 2513
• 22 Inokuchi T, Kawafuchi H. J. Org. Chem. 2006; 71: 947
• 23 Lemek T, Mayr H. J. Org. Chem. 2003; 68: 6880
• 24 Krapcho AP. ARKIVOC 2007; (ii): 1
• 25 Zhao Y, Xia Q, Gamboa da Costa G, Yu H, Cai L, Fu PP. Chem. Res. Toxicol. 2012; 25: 1985
• 26a Pudleiner H, Laatsch H. Liebigs Ann. Chem. 1990; 423
• 26b Gribble GW. Environ. Sci. Pollut. Res. 2000; 7: 37
• 26c Assmann M, Zea S, Köck M. J. Nat. Prod. 2001; 64: 1593
• 26d Davis RA, Fechner GA, Sykes M, Garavelas A, Pass DM, Carroll AR, Addepalli R, Avery VM, Hooper JN. A, Quinn RJ. Bioorg. Med. Chem. 2009; 17: 2497
• 26e Al-Mourabit A, Zancanella MA, Tilvi S, Romo D. Nat. Prod. Rep. 2011; 28: 1229
• 26f Stout EP, Morinaka BI, Wang Y.-G, Romo D, Molinski TF. J. Nat. Prod. 2012; 75: 527
• 26g Wang X, Morinaka BI, Molinski TF. J. Nat. Prod. 2014; 77: 625
• 27 www.sevmexico.com.