Synthesis of Nitrogen Heterocycles by Domino C–N Coupling/Hydroamination Reactions

Peter Langer

doi:10.1055/s-0041-1738384

Synlett, Table of Contents

Synlett 2022; 33(16): 1596-1606
DOI: 10.1055/s-0041-1738384

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Synthesis of Nitrogen Heterocycles by Domino C–N Coupling/Hydroamination Reactions

Peter Langer∗

^aInstitut für Chemie, Universität Rostock, Albert-Einstein-Str. 3a, 18059 Rostock, Germany

^bLeibniz-Institut für Katalyse an der Universität Rostock e. V., Albert-Einstein-Str. 29a, 18059 Rostock, Germany

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Abstract

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Dedicated to Professor Atta-ur-Rahman, PhD, Sc.D, N.I., FRS, FPAS, on the occasion of his 80th birthday

Abstract

The present article presents a personalized Account on the synthesis of nitrogen heterocycles by domino C–N coupling/hydroamination reactions and related processes. The starting materials, 2-alkynyl-1-halohetarenes, are regioselectively available by Sonogashira reactions of various 1,2-dihalogenated heterocycles, such as thiophenes, benzothiophenes, furans and benzofurans, pyridines, quinolines, pyrimidines, and other ring systems. More complex products are formed by domino C–N coupling/hydroamination/C–H arylation reactions of 2-alkynyl-1-halohetarenes with 2-bromoanilines. In these reactions, not only two, but three bonds are formed in one step. In many cases, the products constitute new heterocyclic core structures and show interesting pharmacological or fluorescence properties.

1 Introduction

2 Domino C–N Coupling/Hydroamination Reactions

3 Domino C–N Coupling/Hydroamination/C–H Arylation Reactions

4 Conclusions

Key words

catalysis - cross-coupling - heterocycles - palladium - regioselectivity

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References

References

For reviews of regioselective palladium(0)-catalyzed cross-coupling reactions, see:

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

For an excellent book related to domino reactions, see:

1d Tietze LF, Brasche G, Gericke KM. Domino Reactions in Organic Synthesis . Wiley-VCH; Weinheim: 2006

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

3a Paul F, Patt J, Hartwig JF. J. Am. Chem. Soc. 1994; 116: 5969
3b Guram AS, Buchwald SL. J. Am. Chem. Soc. 1994; 116: 7901

4a Ackermann L. Synlett 2007; 507
4b Ackermann L, Sandmann R, Kondrashov MV. Synlett 2009; 1219
4c Larock RC, Yum EK. J. Am. Chem. Soc. 1991; 113: 6689
4d Larock RC, Yum EK, Refvik MD. J. Org. Chem. 1998; 63: 7652
4e Hegedus LS, Allen GF, Waterman EL. J. Am. Chem. Soc. 1976; 98: 2674

5 Langer P. Synlett 2022; in press; Account DOI:
6 Langer P. Synlett 2022; accepted; Account DOI:
7 Nguyen TH, Hussain M, Malik I, Villinger A, Langer P. Tetrahedron Lett. 2010; 51: 2420
8 Hussain M, Nguyen TH, Langer P. Tetrahedron Lett. 2009; 50: 3929
9 Salman GA, Ali A, Hussain M, Khera RA, Langer P. Synthesis 2011; 2208
10 Salman GA, Nisa RU, Iaroshenko VO, Villinger A, Iqbal J, Ayub K, Langer P. Org. Biomol. Chem. 2012; 10: 9464
11 Salman GA, Hussain M, Iaroshenko VO, Langer P. Adv. Synth. Catal. 2011; 353: 331
12 Ngo TN, Akrawi OA, Dang TT, Villinger A, Langer P. Tetrahedron Lett. 2015; 56: 86
13 Do HH, Villinger A, Lochbrunner S, Ehlers P, Langer P. Tetrahedron 2017; 73: 3407
14 Iaroshenko VO, Mkrtchyan S, Villinger A, Langer P. Synthesis 2012; 45: 205
15 Miliutina M, Ivanov A, Ejaz SA, Iqbal J, Villinger A, Iaroshenko VO, Langer P. RSC Adv. 2015; 5: 60054
16 Miliutina M, Ejaz SA, Khan SU, Iaroshenko VO, Villinger A, Iqbal J, Langer P. Eur. J. Med. Chem. 2017; 126: 408
17 Iaroshenko VO, Knepper I, Zahid M, Dudkin S, Kuzora R, Villinger A, Langer P. Org. Biomol. Chem. 2012; 10: 2955
18 Iaroshenko VO, Zahid M, Mkrtchyan S, Gevorgyan A, Altenburger K, Knepper I, Villinger A, Sosnovskikh VY, Langer P. Tetrahedron 2013; 69: 2309
19 Nguyen TS, Nguyen TA. T, Ponce MB, Ehlers P, Ngo TT, Dang TT, Langer P. Synlett 2020; 31: 1308
20 Pham NN, Dang TT, Ngoc TN, Villinger A, Ehlers P, Langer P. Org. Biomol. Chem. 2015; 13: 6047
21 Ngo TN, Ehlers P, Dang TT, Villinger A, Langer P. Org. Biomol. Chem. 2015; 13: 3321
22 Ngo TN, Janert F, Ehlers P, Hoang DH, Dang TT, Villinger A, Lochbrunner S, Langer P. Org. Biomol. Chem. 2016; 14: 1293
23 Pham NN, Salman GA, Ponce MB, Dang TT, Spannenberg A, Ehlers P, Langer P. Eur. J. Org. Chem. 2017; 3865
24 Pham NN, Salman GA, Belattar N, Dang TT, Ehlers P, Langer P. Eur. J. Org. Chem. 2017; 989
25 Salman GA, Pham NN, Ngo TN, Ehlers P, Villinger A, Langer P. Adv. Synth. Catal. 2017; 359: 1402