Highly Functionalized Pyrrolylpyridines from 2-(Acylethynyl)-pyrroles

Denis N. Tomilin; Lyubov N. Sobenina; Igor A. Ushakov; Boris A. Trofimov

doi:10.1055/s-0040-1706474

Synthesis, Table of Contents

Synthesis 2021; 53(06): 1137-1148
DOI: 10.1055/s-0040-1706474

paper

Highly Functionalized Pyrrolylpyridines from 2-(Acylethynyl)-pyrroles

Authors

Denis N. Tomilin
Lyubov N. Sobenina
Igor A. Ushakov
Boris A. Trofimov∗

A.E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch, Russian Academy of Sciences, 1 Favorsky Street, 664033, Irkutsk, Russia Email: boris_trofimov@irioch.irk.ru

Abstract

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Abstract

A novel family of pharmaceutically prospective, densely functionalized (aryl-, hetaryl-, acyl-, and vinyl-substituted) pyrrolylpyridines has been assembled in up to 95% yields via the amination (NH₄Cl/K₂CO₃/DMSO system, 90 °C, 16 h) of 2-(acylethynyl)pyrroles, followed by cyclization (MeOH, reflux, 6 h, up to 90% yield) of the formed intermediate 1-(pyrrol-2-yl)-1-aminoenones with acetylenic ketones (Bohlmann–Rahtz reaction). The intermediate pyrrolyl aminodienones, prospective building blocks for organic synthesis, can be separately synthesized (DMSO, 90 °C, 6 h) in 70–86% yields. A novel facet of this chemistry is stereoselective synthesis of C-vinylated pyridines, (E)-3-[5-acyl-2-aryl-6-(pyrrol-2-yl)pyridin-3-yl]-1-arylprop-2-en-1-ones, by involving the second molecule of acylacetylene into the reaction.

Key words

2-(acylethynyl)pyrroles - 1-(pyrrol-2-yl)-1-aminoenones - acetylenic ketones - aminodienones - intramolecular cyclization - pyrrolylpyridines

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References

References
1 Lehuédé J, Fauconneau B, Barrier L, Ourakow M, Piriou A, Vierfond J.-M. Eur. J. Med. Chem. 1999; 34: 991

2a Dowell RI, Hadley EM. J. Med. Chem. 1992; 35: 800
2b Raines RT, Vasta J. US 2016280701A1, 2016

3 de Laszlo SE, Visco D, Agarwal L, Chang L, Chin J, Croft G, Forsyth A, Fletcher D, Frantz B, Hacker C, Hanlon W, Harper C, Kostura M, Li B, Luell S, MacCoss M, Mantlo N, O’Neill EA, Orevillo C, Pang M, Parsons J, Rolando A, Sahly Y, Sidler K, Widmer WR, O’Keefe SJ. Bioorg. Med. Chem. Lett. 1998; 8: 2689
4 Chang LL, de Laszlo SE, Kim D, Mantlo NB. EP 0859771A1, 1996
5 Akula M, Sridevi JP, Yogeeswari P, Sriram D, Bhattacharya A. Monatsh. Chem. 2014; 145: 811

6a Klappa JJ, Geers SA, Schmidtke SJ, MacManus-Spencer LA, McNeill K. Dalton Trans. 2004; 883
6b Wang H, Zeng Y, Ma JS, Fu H, Yao J, Mikhaleva AI, Trofimov BA. Chem. Commun. 2009; 5457
6c Pucci D, Aiello I, Aprea A, Bellusci A, Crispini A, Ghedini M. Chem. Commun. 2009; 1550
6d Annunziata L, Pappalardo D, Tedesco C, Pellecchia C. Macromolecules 2009; 42: 5572
6e Gowda AS, Petersen JL, Milsmann C. Inorg. Chem. 2018; 57: 1919

7 Yadav S, Singh A, Rashid N, Ghotia M, Roy TK, Ingole PP, Ray S, Mobin SM, Dash C. ChemistrySelect 2018; 3: 9469
8 Chen J.-J, Xu Y.-C, Gan Z.-L, Peng X, Yi X.-Y. Eur. J. Inorg. Chem. 2019; 2019: 1733
9 García MA, Farrán MA, María DS, Claramunt RM, Torralba MC, Torres MR, Jaime C, Elguero J. Molecules 2015; 20: 9862

10a Sobenina LN, Sagitova EF, Markova MV, Ushakov IA, Ivanov AV, Trofimov BA. Tetrahedron Lett. 2018; 59: 4047
10b Sagitova EF, Sobenina LN, Tomilin DN, Markova MV, Ushakov IA, Trofimov BA. Mendeleev Commun. 2019; 29: 252

11a Trofimov BA, Stepanova ZV, Sobenina LN, Mikhaleva AI, Ushakov IA. Tetrahedron Lett. 2004; 45: 6513
11b Trofimov BA, Sobenina LN. Targets in Heterocyclic Systems, Vol. 13. Attanasi OA, Spinelli D. Società Chimica Italiana; Roma: 2009: 92-119
11c Sobenina LN, Tomilin DN, Petrova OV, Gulia N, Osowska K, Szafert S, Mikhaleva AI, Trofimov BA. Russ. J. Org. Chem. 2010; 46: 1373
11d Gotsko MD, Sobenina LN, Tomilin DN, Ushakov IA, Dogadina AV, Trofimov BA. Tetrahedron Lett. 2015; 56: 4657
11e Tomilin DN, Pigulski B, Gulia N, Arendt A, Sobenina LN, Mikhaleva AI, Szafert S, Trofimov BA. RSC Adv. 2015; 5: 73241
11f Tomilin DN, Gotsko MD, Sobenina LN, Ushakov IA, Afonin AV, Soshnikov DY, Trofimov AB, Koldobsky AB, Trofimov BA. J. Fluorine Chem. 2016; 186: 1
11g Pigulski B, Arendt A, Tomilin DN, Sobenina LN, Trofimov BA, Szafert S. J. Org. Chem. 2016; 81: 9188

12a Bagley MC, Chapaneri K, Dale JW, Xiong X, Bower J. J. Org. Chem. 2005; 70: 1389
12b Yang T, Deng Z, Wang K.-H, Li P, Huang D, Su Y, Hu Y. J. Org. Chem. 2020; 85: 924

13 Bagley MC, Glover C, Merritt EA. Synlett 2007; 2459

14a Wlochal J, Davies RD. M, Burton J. Org. Lett. 2014; 16: 4094
14b Christy MP, Johnson T, McNerlin CD, Woodard J, Nelson AT, Lim B, Hamilton TL, Freiberg KM, Siegel D. Org. Lett. 2020; 22: 2365
14c Marvadi SK, Krishna VS, Surineni G, Srilakshmi Reshma R, Sridhar B, Sriram D, Kantevari S. Bioorg. Chem. 2020; 96: 103626

15a Yoshimatsu M, Tanaka M, Fujimura Y, Ito Y, Goto Y, Kobayashi Y, Wasada H, Hatae N, Tanabe G, Muraoka O. J. Org. Chem. 2015; 80: 9480
15b Noriyuki H, Yoko S, Kohei Y, Chiaki O, Mitsuhiro Y, Teruki Y. Heterocycles 2017; 95: 557

16 Sobenina LN, Tomilin DN, Sagitova EF, Ushakov IA, Trofimov BA. Org. Lett. 2017; 19: 1586

Supplementary Material

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