Arylation of Pyridines via Suzuki–Miyaura Cross-Coupling and Pyridine-­Directed C–H Activation Using a Continuous-Flow Approach

Maria Christakakou; Michael Schön; Michael Schnürch; Marko D. Mihovilovic

doi:10.1055/s-0033-1339870

Synlett, Inhaltsverzeichnis

Synlett 2013; 24(18): 2411-2418
DOI: 10.1055/s-0033-1339870

letter

Arylation of Pyridines via Suzuki–Miyaura Cross-Coupling and Pyridine-Directed C–H Activation Using a Continuous-Flow Approach

Maria Christakakou

Institute of Applied Synthetic Chemistry, Vienna University of Technology, Getreidemarkt 9/163-OC, 1060 Vienna, Austria Fax: +43(1)588019163616 eMail: michael.schnuerch@tuwien.ac.at

,

Michael Schön

Institute of Applied Synthetic Chemistry, Vienna University of Technology, Getreidemarkt 9/163-OC, 1060 Vienna, Austria Fax: +43(1)588019163616 eMail: michael.schnuerch@tuwien.ac.at

,

Michael Schnürch*

Institute of Applied Synthetic Chemistry, Vienna University of Technology, Getreidemarkt 9/163-OC, 1060 Vienna, Austria Fax: +43(1)588019163616 eMail: michael.schnuerch@tuwien.ac.at

,

Marko D. Mihovilovic

Institute of Applied Synthetic Chemistry, Vienna University of Technology, Getreidemarkt 9/163-OC, 1060 Vienna, Austria Fax: +43(1)588019163616 eMail: michael.schnuerch@tuwien.ac.at

› Institutsangaben

Abstract

Alle Artikel dieser Rubrik

Dedicated to Professor Manfred Schlosser who is missing in the Swiss alps he loved so much

Abstract

Suzuki–Miyaura cross-coupling reactions between heteroaryl bromides and arylboronic acids were performed employing a continuous-flow approach using a simple flow reactor designed in-house. Pd(PPh₃)₄ was used as catalyst, and arylboronic acids containing both electron-withdrawing and electron-donating groups were applied. The coupling process required 23 minutes of residence time to be completed and generally good yields were obtained. Subsequent arylation of 2-phenyl pyridine was carried out via a C–H activation strategy using substituted bromobenzene compounds and a ruthenium(II) catalyst. To the best of our knowledge in this work we present for the first time the possibility of performing intermolecular C–H activation in a continuous-flow system.

Key words

heterocycles - cross coupling - flow chemistry - C–H activation - catalysis

Volltext

Referenzen

References and Notes

1a Baumann M, Baxendale IR, Ley SV, Nikbin N. Beilstein J. Org. Chem. 2011; 7: 442
1b Heterocycles in Life and Society: An Introduction to Heterocyclic Chemistry and Biochemistry and the Role of Heterocycles in Science, Technology, Medicine, and Agriculture. Pozharsky AF, Soldatenkov AT, Katritzky AR. John Wiley and Sons; Chichester: 1997
1c Bellus D. Lect. Heterocycl. Chem. 1987; 9: 65
1d Muller T, Bräse S. Angew. Chem. Int. Ed. 2011; 50: 11844
1e Rasmussen SC, Schwiderski RL, Mulholland ME. Chem. Commun. 2011; 47: 11394
1f Maly KE. J. Mat. Chem. 2009; 19: 1781
1g Elbing M, Bazan GC. Angew. Chem. Int. Ed. 2008; 47: 834

For reviews on cross-coupling on heterocyclic substrates, see:

2a Schnürch M, Flasik R, Khan AF, Spina M, Mihovilovic MD, Stanetty P. Eur. J. Org. Chem. 2006; 3283
2b Schroeter S, Stock C, Bach T. Tetrahedron 2005; 61: 2245
2c Wang J.-R, Manabe K. Synthesis 2009; 1405
2d Djakovitch L, Batail N, Genelot M. Molecules 2011; 16: 5241
2e Slagt VF, de Vries AH. M, de Vries JG, Kellog RM. Org. Process Res. Dev. 2010; 14: 30
2f Fairlamb IJ. S. Chem. Soc. Rev. 2007; 36: 1036
2g Banwell MG, Goodwin TE, Ng S, Smith JA, Wong DJ. Eur. J. Org. Chem. 2006; 3043
2h Nicolaou KC, Bulger PG, Sarlah D. Angew. Chem. Int. Ed. 2005; 44: 4442
2i Magano J, Dunetz JR. Chem. Rev. 2011; 111: 2177

3 Noël T, Buchwald SL. Chem. Soc. Rev. 2011; 40: 5010
4 Glasnov TN, Kappe CO. Adv. Synth. Catal. 2010; 352: 3089

5a Baxendale IR, Hayward JJ, Lanners S, Ley SV, Smith CD In Microreactors in Organic Synthesis and Catalysis. Wirth T. Wiley-VCH; Weinheim: 2008: 84-122
5b Irfan M, Glasnov TN, Kappe CO. ChemSusChem 2011; 4: 300

For selected examples, see:

6a Kirschning A, Solodenko W, Mennecke K. Chem. Eur. J. 2006; 12: 5972
6b Wegner J, Ceylan S, Kirschning A. Adv. Synth. Catal. 2012; 354: 17
6c Solodenko W, Wen H, Leue S, Stuhlmann F, Sourkouni-Argirusi G, Jas G, Schönfeld H, Kunz U, Kirschning A. Eur. J. Org. Chem. 2004; 3601
6d He P, Haswell SJ, Fletcher PD. I. Appl. Catal., A 2004; 274: 111
6e Wilson NS, Sarko CR, Roth GP. Org. Process Res. Dev. 2004; 8: 535
6f Baxendale IR, Griffiths-Jones CM, Ley SV, Tranmer GK. Chem. Eur. J. 2006; 12: 4407
6g Nagaki A, Kenmoku A, Moriwaki Y, Hayashi A, Yoshida J.-i. Angew. Chem. Int. Ed. 2010; 49: 7543
6h Noel T, Musacchio AJ. Org. Lett. 2011; 13: 5180
6i Noel T, Kuhn S, Musacchio AJ, Jensen KF, Buchwald SL. Angew. Chem. Int. Ed. 2011; 50: 5943

7a Lyons TW, Sanford MS. Chem. Rev. 2010; 110: 1147
7b Chen X, Engle KM, Wang D.-H, Yu J.-Q. Angew. Chem. Int. Ed. 2009; 48: 5094

8 Zhang L, Geng M, Teng P, Zhao D, Lu X, Li J.-X. Ultrason. Sonochem. 2012; 19: 250

For reviews on C–H activation, see:

9a Engle KM, Mei T.-S, Wasa M, Yu J.-Q. Acc. Chem. Res. 2012; 45: 788
9b Du Bois J. Chemtracts 2005; 18: 1
9c Davies HM. L, Loe O. Synthesis 2004; 16: 2595
9d Davies HM. L, Beckwith RE. J. Chem. Rev. 2003; 103: 2861
9e Godula K, Sames D. Science 2006; 312: 67
9f Yeung CS, Dong VM. Chem. Rev. 2011; 111: 1215
9g Zhang C, Tang T, Jiao N. Chem. Soc. Rev. 2012; 41: 3464
9h Ackermann L. Chem. Rev. 2011; 111: 1315
9i Jazzar R, Hitce J, Renaudat A, Sofack-Kreitzer J, Baudoin O. Chem. Eur. J. 2010; 16: 2654
9j Schnürch M, Dastbaravardeh N, Ghobrial M, Mrozek B, Mihovilovic MD. Curr. Org. Chem. 2011; 15: 2694

10a Sersen S, Kljun J, Pozgan F, Stefane B, Turel I. Organometallics 2013; 32: 609
10b Pozgan F, Dixneuf PH. Adv. Synth. Catal. 2009; 351: 1737
10c Oezdemir I, Demir S, Cetinkaya B, Gourlaouen C, Maseras F, Bruneau C, Dixneuf PH. J. Am. Chem. Soc. 2008; 130: 1156
10d Oi S, Fukita S, Inoue Y. Chem. Commun. 1998; 2439
10e Yu B, Yan X, Wang S, Tang N, Xi C. Organometallics 2010; 29: 3222
10f Yoshikai N, Matsumoto A, Norinder J, Nakamura E. Synlett 2010; 313
10g Prades A, Poyatos M, Peris E. Adv. Synth. Catal. 2010; 352: 1155

11a Hartman RL, Naber JR, Zaborenko N, Buchwald SL, Jensen KV. Org. Process Res. Dev. 2010; 14: 1347
11b Noel T, Naber JR, Hartman RL, McMullen JP, Jensen KF, Buchwald SL. Chem. Sci. 2011; 2: 287
11c Kuhn S, Noel T, Gu L, Heider PL, Jensen KV. Lab-on-a-Chip 2011; 11: 2488

12a Koley M, Dastbaravardeh N, Schnürch M, Mihovilovic MD. ChemCatChem 2012; 4: 1696
12b Chu J.-H, Tsai S.-L, Wu M.-J. ChemInform 2010; 41: 3757

For reviews, see:

13a Wencel-Delord J, Droge T, Liu F, Glorius F. Chem. Soc. Rev. 2011; 40: 4740
13b Arockiam PB, Bruneau C, Dixneuf PH. Chem. Rev. 2012; 112: 5879
13c Ritleng V, Sirlin C, Pfeffer M. Chem. Rev. 2002; 102: 1731
13d Kakiuchi F, Chatani N. Ruthenium-Catalyzed Reactions via sp C–H, sp² C–H, sp³ C–H, and C–Halogen Bond Activations. In Ruthenium in Organic Synthesis. Murahashi S.-I. Wiley-VCH; Weinheim: 2004: 219-255

14 Oi S, Funayama R, Hattori T, Inoue Y. Tetrahedron 2008; 64: 6051
15 Oi S, Fukita S, Hirata N, Watanuki N, Miyano S, Inoue Y. Org. Lett. 2001; 3: 2579

16a Dastbaravardeh N, Kirchner K, Schnürch M, Mihovilovic MD. J. Org. Chem. 2012; 78: 658
16b Dastbaravardeh N, Schnürch M, Mihovilovic MD. Eur. J. Org. Chem. 2013; 2878
16c Dastbaravardeh N, Schnürch M, Mihovilovic MD. Org. Lett. 2012; 14: 1930
16d Dastbaravardeh N, Schnürch M, Mihovilovic MD. Org. Lett. 2012; 14: 3792

17 Preparation of 2-Aryl- and 3-Aryl Derivatives 3a–f and 5a–f To a round-bottomed flask was added the appropriate amount of 2-bromo- or 3-bromopyridine (1 or 4, 1 equiv, 1 mmol), boronic acid 2a–f (1.2 equiv, 1.2 mmol), K₂CO₃ (2 equiv, 276 mg, 2 mmol), Pd(PPh₃)₄ (2.1 mol%, 24 mg, 0.021 mmol), and a dioxane–H₂O mixture as solvent (1:1, 20 mL). The mixture was stirred for 5 min at r.t. and was then filtered through filter paper, before being transferred to the syringe pump. The residence time was 23 min, and the temperature of the heating plate was set to 90 °C. The inner diameter of the capillary was 1 mm. The flow rate was 0.695 mL/min, and the volume of the reactor was 16 mL. Reference NMR Spectra for 2-(4-methoxyphenyl)-pyridine (3d) ¹H (200 MHz CDCl₃): δ = 3.86 (s, 3 H), 6.95–7.05 (m, 2 H), 7.13–7.23 (m, 1 H), 7.62–7.79 (m, 2 H), 7.90–8.01 (m, 2 H), 8.60–8.71 (m, 1 H). ¹³C (50 MHz, CDCl₃): δ = 55.5 (q), 114.3 (d), 120.0 (d), 121.6 (d), 128.3 (d), 132.1 (s), 136.9 (d), 149.6 (d), 157.2 (s), 160.6 (s). Preparation of ortho-Arylated 2-Phenylpyridine Derivatives 7a–e, 8a–f To a round-bottomed flask was added the appropriate amount of 2-arylpyridine derivative 7a or 7b (1 equiv, 0.25 mmol), the appropriate bromobenzene derivative 6a–e (3 equiv, 0.75 mmol), DBU (4 equiv, 152 mg, 1 mmol), Ph₃P (10 mol%, 6.5 mg, 0.025 mmol), dichloro(p-cymene)ruthenium(II) dimer [5 mol%, 7.6 mg, 0.0125 mmol; with the exception of the synthesis of 8f, in which 7.5 mol% of dichloro(p-cymene)ruthenium(II) dimer were used (7.5 mol%, 11.5 mg, 0.01875 mmol) and NMP as solvent (1 mL)]. The mixture was stirred at r.t. until complete dissolution of all reagents. Then this solution was transferred to the syringe pump system. The flow rate was set to 0.533 mL/min which corresponded to a residence time of 30 min, and the temperature of the heating plate was set to 160 °C. After pumping through the reaction mixture, 20 mL pure solvent was pumped through as well. The inner diameter of the capillary was 1 mm. The volume of the reactor was 16 mL. Reference NMR spectra for 2-[4′-methoxy-(1,1′-biphenyl)-2-yl]pyridine (7b) ¹H (200MHz, CDCl₃): δ = 3.78 (s, 3 H), 6.72–6.82 (m, 2 H), 6.90 (dt, J = 7.8, 1.0 Hz, 1 H), 7.01–7.15 (m, 3 H), 7.33–7.50 (m, 4 H), 7.61–7.73 (m, 1 H). ¹³C (50 MHz, CDCl₃): δ = 55.3 (q), 113.7 (d), 121.4 (d), 125.6 (d), 127.4 (d), 128.6 (d), 130.6 (d), 130.6 (d), 130.9 (d), 133.8 (s), 135.4 (d), 139.5 (s), 140.3 (s), 149.6 (d), 158.6 (s), 159.6 (s).

Zusatzmaterial

Supporting Information

Arylation of Pyridines via Suzuki–Miyaura Cross-Coupling and Pyridine-­Directed C–H Activation Using a Continuous-Flow Approach

Arylation of Pyridines via Suzuki–Miyaura Cross-Coupling and Pyridine-Directed C–H Activation Using a Continuous-Flow Approach