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DOI: 10.1055/s-0040-1719906
Cross-Coupling Reactions of Polyhalogenated Heterocycles
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In memoriam of Prof. Dr. Tamás Patonay
Abstract
Palladium-catalyzed cross-coupling reactions of polyhalogenated heterocycles provide a convenient access to multifold arylated and alkynylated ring systems with a broad spectrum of physical and medicinal properties. Products include thiophenes, selenophenes, pyrroles, indoles, furans, benzofurans, pyrazoles, pyridines, quinolines, pyrimidines, pyrazines, naphthyridines, quinoxalines, and others. The regioselectivity of the coupling reactions is controlled by a combination of electronic and steric parameters. While a number of couplings can be carried out essentially under standard conditions, others require the use of more sophisticated ligands and a thorough optimization of the conditions, such as solvent, temperature, or reaction time. The present Account provides a personalized overview of coupling reactions of polyhalogenated heterocycles.
1 Introduction
2 Thiophenes
3 Selenophenes
4 Pyrroles and Indoles
5 Furans and Benzofurans
6 Pyrazoles
7 Pyridines
8 Quinolines
9 Pyrimidines and Pyrazines
10 Naphthyridines and Quinoxalines
11 Miscellaneous
12 Conclusions
Publikationsverlauf
Eingereicht: 31. Januar 2022
Angenommen: 08. Februar 2022
Artikel online veröffentlicht:
24. März 2022
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References
- 1a Schröter S, Stock C, Bach T. Tetrahedron 2005; 61: 2245
- 1b Schnürch M, Flasik R, Khan AF, Spina M, Mihovilovic MD, Stanetty P. Eur. J. Org. Chem. 2006; 3283
- 1c Wang R, Manabe K. Synthesis 2009; 1405
- 2 For a simple guide for the prediction of the site-selectivity of palladium-catalyzed cross-coupling reactions based on 1H NMR data of the nonhalogenated derivatives, see: Handy ST, Zhang Y. Chem. Commun. 2006; 299
- 3 Review: Hussain M, Sung TV, Langer P. Synlett 2012; 23: 2735
- 4 Review: Hassan Z, Patonay T, Langer P. Synlett 2013; 24: 412
- 5a Araki K, Endo H, Masuda G, Ogawa T. Chem. Eur. J. 2004; 10: 3331
- 5b Janda M, Srogl J, Stibor I, Nemec M, Vopatrna P. Synthesis 1972; 545
- 6 Neenan X, Whitesides GM. J. Org. Chem. 1988; 53: 2489
- 7 Dang TT, Rasool N, Dang TT, Reinke H, Langer P. Tetrahedron Lett. 2007; 48: 845
- 8 Dang TT, Dang TT, Rasool N, Villinger A, Langer P. Adv. Synth. Catal. 2009; 351: 1595
- 9 Wang L, Groβe T, Stevens H, Brinkhoff T, Simon M, Liang L, Bitzer J, Bach G, Zeeck A, Tokuda H, Lang S. Appl. Microbiol. Biotechnol. 2006; 72: 816
- 10a Fukada T, Sud E.-i, Shimokawa K, Iwao M. Tetrahedron 2008; 64: 328
- 10b Boger DL, Boyer CW, Labroli MA, Sehon CA, Jin Q. J. Am. Chem. Soc. 1999; 121: 54
- 10c Fürstner A, Weintritt H, Hupperts A. J. Org. Chem. 1994; 60: 6637
- 11 Toguem S.-MT, Knepper I, Ehlers P, Dang TT, Patonay T, Langer P. Adv. Synth. Catal. 2012; 354: 1819
- 12 Toguem S.-MT, Villinger A, Langer P. Synlett 2009; 3311
- 13 Toguem S.-MT, Malik I, Hussain M, Iqbal J, Villinger A, Langer P. Tetrahedron 2013; 69: 160
- 14 Toguem S.-MT, Villinger A, Langer P. Synlett 2009; 909
- 15 Helmholdt RB, Sonneveld EJ, Van de Velde CM. L, Blockhuys F, Lenstra AT. H, Geise HJ, Peschar R. Acta Crystallogr., Sect. B: Struct. Sci. 2007; 63: 783
- 16 Dang TT, Villinger A, Langer P. Adv. Synth. Catal. 2008; 350: 2109
- 17 Ehlers P, Dang TT, Patonay T, Villinger A, Langer P. Eur. J. Org. Chem. 2013; 2000
- 18 Gilow HM, Burton DE. J. Org. Chem. 1981; 46: 2221
- 19 Dang TT, Dang TT, Ahmad R, Reinke H, Langer P. Tetrahedron Lett. 2008; 49: 1698
- 20 Ullah F, Dang TT, Heinicke J, Villinger A, Langer P. Synlett 2009; 838
- 21 Toguem S.-MT, Fatunsin O, Villinger A, Langer P. Tetrahedron Lett. 2011; 52: 3732
- 22 Toguem S.-MT, Langer P. Synlett 2011; 513
- 23 Hussain M, Dang TT, Langer P. Synlett 2009; 1822
- 24 Ibad MF, Hussain M, Abid O.-u.-R, Ali A, Ullah I, Zinad DS, Langer P. Synlett 2010; 411
- 25a Liu Y, Gribble GW. Tetrahedron Lett. 2000; 41: 8717
- 25b Liu Y, Gribble GW. Tetrahedron Lett. 2002; 43: 7135
- 26 Ibad MF, Zinad DS, Hussain M, Ali A, Villinger A, Langer P. Tetrahedron 2013; 69: 7492
- 27 Hussain MS.-M. T, Ahmad R, Tung DT, Knepper I, Villinger A, Langer P. Tetrahedron 2011; 67: 5304
- 28 Shopee CW. J. Chem. Soc., Perkin Trans. 1 1985; 45
- 29 Hussain M, Khera RA, Nguyen TH, Langer P. Org. Biomol. Chem. 2011; 9: 370
- 30 Malik I, Ahmad Z, Reimann S, Nawaz M, Patonay T, Langer P. Synlett 2012; 23: 1463
- 31 Gonzalez-Diaz H, Agueero G, Cabrera MA, Molina R, Santana L, Uriarte E, Delogu G, Castañedo N. Bioorg. Med. Chem. Lett. 2005; 15: 551 ; and references cited therein
- 32 Dang TT, Dang TT, Langer P. Synlett 2006; 2812
- 33 Nguyen TH, Hussain M, Malik I, Villinger A, Langer P. Tetrahedron Lett. 2010; 51: 2420
- 34 Hussain M, Nguyen TH, Langer P. Tetrahedron Lett. 2009; 50: 3929
- 35 Salman GA, Ali A, Hussain M, Khera RA, Langer P. Synthesis 2011; 2208
- 36 Khera RA, Ali A, Hussain M, Tatar J, Villinger A, Langer P. Synlett 2010; 1923
- 37 Khera RA, Ali A, Rafique H, Hussain M, Tatar J, Abbas N, Saeed A, Villinger A, Langer P. Tetrahedron 2011; 67: 5244
- 38 Toguem S.-MT, Langer P. Synlett 2010; 1779
- 39 Ehlers P, Reimann S, Erfle S, Villinger A, Langer P. Synlett 2010; 1528
- 40 Reimann S, Ehlers P, Petrosyan A, Kohse S, Spannenberg A, Surkus AE, Ghochikyan TV, Saghyan AS, Lochbrunner S, Kühn S, Ludwig R, Langer P. Adv. Synth. Catal. 2014; 356: 1987
- 41 Ehlers P, Neubauer A, Lochbrunner S, Villinger A, Langer P. Org. Lett. 2011; 13: 1618
- 42 Rivera RP, Ehlers P, Ohlendorf L, Rodríguez ET, Villinger A, Langer P. Eur. J. Org. Chem. 2018; 990
- 43 Rivera RP, Ehlers P, Ohlendorf L, Ponce MB, Rodríguez ET, Langer P. Tetrahedron 2019; 75: 130559
- 44 Reimann S, Ehlers P, Parpart S, Surkus A, Spannenberg A, Langer P. Tetrahedron 2015; 71: 5371
- 45 Ehlers P, Hakobyan A, Neubauer A, Lochbrunner S, Langer P. Adv. Synth. Catal. 2013; 355: 1849
- 46 Ehlers P, Petrosyan A, Neubauer A, Bröse T, Lochbrunner S, Ghochikyan TV, Saghyan AS, Langer P. Org. Biomol. Chem. 2014; 12: 8627
- 47 Chem TK, Flowers WT. J. Chem. Soc., Chem. Commun. 1980; 1139
- 48 Reimann S, Parpart S, Ehlers P, Sharif M, Spannenberg A, Langer P. Org. Biomol. Chem. 2015; 13: 6832
- 49 Reimann S, Ehlers P, Ohlendorf L, Langer P. Org. Biomol. Chem. 2017; 15: 1510
- 50 Ahmed S, Sharif M, Shoaib K, Reimann S, Iqbal J, Spannenberg A, Langer P. Tetrahedron Lett. 2013; 54: 1669
- 51 Ali I, Siyo B, Hassan Z, Malik I, Ullah I, Ali A, Nawaz M, Iqbal J, Patonay T, Villinger A, Langer P. J. Fluorine Chem. 2013; 145: 18
- 52 Sharif M, Shoaib K, Ahmed S, Iqbal J, Abilov ZA, Spannenberg A, Langer P. Tetrahedron Lett. 2016; 57: 3060
- 53 Khaddour Z, Akrawi OA, Hamdy AM, Suleiman A, Jamous K, Villinger A, Langer P. Tetrahedron Lett. 2015; 56: 554
- 54 Eleya N, Mahal A, Villinger A, Langer P. Adv. Synth. Catal. 2011; 353: 2761
- 55 Akrawi OA, Mohammed HH, Langer P. Synlett 2013; 24: 1121
- 56 Marull M, Schlosser M. Eur. J. Org. Chem. 2003; 1576
- 57 Rivera RP, Hassan S, Ejaz SA, Ehlers P, Lecka J, Sévigny J, Rodríguez ET, Iqbal J, Langer P. ChemistrySelect 2018; 3: 8587
- 58 Kuhrt D, Ejaz SA, Afzal S, Khan SU, Lecka J, Sévigny J, Ehlers P, Spannenberg A, Iqbal J, Langer P. Eur. J. Med. Chem. 2017; 816
- 59 Hussain M, Hung NT, Khera RA, Malik I, Zinad DS, Langer P. Adv. Synth. Catal. 2010; 352: 1429
- 60 Malik I, Ahmed Z, Reimann S, Ali I, Villinger A, Langer P. Eur. J. Org. Chem. 2011; 2088
- 61 Fleischhauer J, Zahn S, Beckert R, Grummt UW, Birckner E, Görls H. Chem. Eur. J. 2012; 18: 4549
- 62 Petrosyan A, Ehlers P, Reimann S, Ghochikyan TV, Saghyan AS, Spannenberg A, Lochbrunner S, Langer P. Tetrahedron 2015; 71: 6803
- 63 Petrosyan A, Ehlers P, Ghochikyan TV, Saghyan AS, Lochbrunner S, Langer P. Org. Biomol. Chem. 2016; 14: 1442
- 64 Newkome GR, Garbis SJ, Majestic VK, Fronczek FR, Chiari G. J. Org. Chem. 1981; 46: 833
- 65 Ehlers P, Petrosyan A, Ghochikyan TV, Saghyan AS, Neubauer A, Lochbrunner S, Langer P. Synlett 2013; 24: 359
- 66 Ali I, Hassan Z, Hein M, Falodun A, Patonay T, Villinger A, Langer P. Synthesis 2012; 44: 2255
- 67 Täufer T, Ehlers P, Langer P. Tetrahedron 2022; 103: 132537
- 68 Ali I, Siyo B, Al Soud Y, Villinger A, Langer P. Synthesis 2012; 44: 1637
- 69 Hamdy AM, Eleya N, Mohammed HH, Patonay T, Villinger A, Langer P. Tetrahedron 2013; 69: 2081
- 70 Hamdy AM, Al-Masoudi NA, Pannecouque C, Rahman Q, Villinger A, Langer P. RSC Adv. 2015; 5: 107360
- 71 Kuhrt D, Ehlers P, Spannenberg A, Langer P. Synlett 2020; 31: 1277
- 72 Modh RP, De Clercq E, Pannecouque C, Chikhalia KH. J. Enzym. Inhib. Med. Chem. 2014; 29: 100
- 73 Keri RS, Quintanova C, Marques SM, Esteves AR, Cardoso SM, Santos MA. Bioorg. Med. Chem. 2013; 21: 4559
- 74 Tka N, Ayed MA. H, Braiek MB, Jabli M, Langer P. Beilstein J. Org. Chem. 2021; 17: 2450
- 75 Tka N, Ayed MA. H, Braiek MB, Jopp S, Jabli M, Langer P. Beilstein J. Org. Chem. 2021; 17: 1629
- 76 Akrawi O, Nagy G, Patonay T, Villinger A, Langer P. Tetrahedron Lett. 2012; 53: 3206
- 77 Akrawi OA, Patonay T, Kónya K, Langer P. Synlett 2013; 24: 860
- 78 Pajtás D, Dihen K, Patonay T, Kónya K, Villinger A, Langer P. Synlett 2015; 26: 2601
- 79 Jordán S, Pajtás D, Patonay T, Langer P, Kónya K. Synthesis 2017; 83: 1983
For reviews of regioselective palladium(0)-catalyzed cross-coupling reactions, see:
For metal–halide exchange, see: