Direct and Efficient Synthesis of Pyrrole-3-carbaldehydes by Vilsmeier–Haack Formylation of Pyrroles with Sterically Crowded Amides

Abstract

A simple and convenient synthetic method to prepare N-substituted pyrrole-3-carbaldehydes by Vilsmeier–Haack formylation of pyrroles using sterically crowded formamides was developed. The dependence of the formylation regioselectivity on steric features of substrates and reagents is discussed.

Key words

formylation - pyrroles - aldehydes - electrophilic aromatic substitution - formamides - Vilsmeier–Haack

• References

• 1 Jones MA, Morton JD, Coxon JM, McNabb SB, Lee HY.-Y, Aitken SG, Mehrtens JM, Robertson LJ. G, Neffe AT, Miyamoto S, Bickerstaffe R, Gately K, Wood JM, Abell AD. Bioorg. Med. Chem. 2008; 16: 6911
• 2 Berglund S, Egner BJ, Graden H, Graden J, Inghardt T, Morgan DG. A, Giordanetto F. Bioorg. Med. Chem. Lett. 2008; 18: 4859
• 3 Cremonesi S, Di Fabio R, Gentile G, Micheli F, Pasquarello A, Tarsi L, Terreni S, Tonelli F, Pozzan A, Arban R, Bianchi F, Buson A. Bioorg. Med. Chem. Lett. 2010; 20: 5044
• 4 Candy CF, Jones RA, Wright PH. J. Chem. Soc. C 1970; 2563
• 5 Sum F.-W, Dusza J, Santos ED, Grosu G, Reich M, Du X, Albright JD, Chan P, Coupet J, Ru X, Mazandarani H, Saunders T. Bioorg. Med. Chem. Lett. 2003; 13: 2195
• 6 Noland WE, Lanzatella NP, Venkatraman L, Anderson NF, Gullickson GC. J. Heterocycl. Chem. 2009; 46: 1154
• 7 Nenajdenko VG, Reznichenko AL, Balenkova ES. Tetrahedron 2007; 63: 3031
• 8 Cadogan JI. G, Hewage CM, McNab H, MacPherson AD, Nicolson IS, Reed D, Sadler IH. Org. Biomol. Chem. 2006; 4: 2446
• 9 Hrncarikova K, Vegh D. Molecules 2003; 8: 536
• 10 Massa S, Stefancich G, Artico M, Corelli F, Ortenzi G. Heterocycles 1985; 23: 1417
• 11 Chadwick DJ, Hodgson ST. J. Chem. Soc., Perkin Trans. 1 1983; 93
• 12 Downie IM, Earle MJ, Heaney H, Shuhaibar KF. Tetrahedron 1993; 49: 4015
• 13 Campiani G, Nacci V, Corelli F, Anzini M. Synth. Commun. 1991; 21: 1567
• 14 Shan WG, Shi XJ, Su WK. Org. Prep. Proced. Int. 2004; 36: 337
• 15 Kakushima M, Hamel P, Frenette R, Rokach J. J. Org. Chem. 1983; 48: 3214
• 16 Tressl R, Wondrak GT, Garbe L.-A, Krueger R.-P, Rewicki D. J. Agric. Food Chem. 1998; 46: 1765
• 17 Purkarthofer T, Gruber K, Fechter MH, Griengl H. Tetrahedron 2005; 61: 7661
• 18 Bray BL, Mathies PH, Naef R, Solas DR, Tidwell TT, Artis DR, Muchowski JM. J. Org. Chem. 1990; 55: 6317
• 19 Dallemagne SR, Fabis F, Dumoulin H, Robba M. Synth. Commun. 1994; 24: 1855
• 20 Dumoulin H, Rault S, Robba M. J. Heterocycl. Chem. 1996; 33: 255
• 21 Carson JR, Davis NM. J. Org. Chem. 1981; 46: 839
• 22 Pina MC, Budilin VA, Rodrigues M, Bundel YuG. Chem. Heterocycl. Compd. (Engl. Transl.) 1989; 25: 268
• 23 Kevin NJ, Duffy JL, Kirk BA, Chapman KT, Schleif WA, Olsen DB, Stahlhut M, Rutkowski CA, Kuo LC, Jin L, Lin JH, Emini EA, Tata JR. Bioorg. Med. Chem. Lett. 2003; 13: 4027
• 24 Glennon RA, Chaurasia C, Titeler M. J. Med. Chem. 1990; 33: 2777
• 25 Lubisch W, Behl B, Hofmann HP. Bioorg. Med. Chem. Lett. 1997; 7: 1101
• 26 Karousis N, Liebscher J, Varvounis G. Synthesis 2006; 1494
• 27 Ojika M, Shizuri Y, Niwa H, Yamada K, Iwadare S. Tetrahedron Lett. 1982; 23: 4977
• 28 Xiao D, Ketcha DM. Org. Prep. Proced. Int. 1995; 27: 503
• 29 Haldar P, Barman G, Ray JK. Tetrahedron 2007; 63: 3049
• 30 Gross H. Chem. Ber. 1962; 95: 2270
• 31 Yankovskaya LA, Yufit SS In Organic Synthesis in Two-Phase Systems . Khimiya; Moscow: 1982: 81
• 32 Vougioukalakis GC, Grubbs RH. J. Am. Chem. Soc. 2008; 130: 2234
• 33 Robson JH, Reinhart J. J. Am. Chem. Soc. 1955; 77: 498
• 34 Hodgson DM, Bray CD, Kindon ND, Reynolds NJ, Coote SJ, Um JM, Houk KN. J. Org. Chem. 2009; 74: 1019
• 35 Pictet A, Crepieux P. Ber. Dtsch. Chem. Ges. 1888; 21: 1106
• 36 Mangiapan S, Benfenati E, Grasso P, Terreni M, Pregnolato M, Pagani G, Barcelo D. Environ. Sci. Technol. 1997; 31: 3637
• 37 Reddelien G, Thurm A. Ber. Dtsch. Chem. Ges. B 1932; 65: 1511
• 38 Aroney MJ, Le Fèvre RJ. W, Singh AN. J. Chem. Soc. 1965; 3179
• 39 Chakrabarti JK, Tupper DE. J. Heterocycl. Chem. 1974; 11: 417