Triazole-Enabled Ruthenium(II) Carboxylate-Catalyzed C–H Arylation with Electron-Deficient Aryl Halides

Abstract

A triazole-directed direct C–H arylation of arenes with electron-deficient aryl halides or a synthetically useful pyrimidyl chloride was achieved through ruthenium catalysis. Our novel strategy provides operationally simple and environmentally benign access to highly functionalized hetarenes, avoiding the use of strong organometallic bases. Detailed studies revealed a significant effect of the phosphine ligand, thereby permitting the reaction to occur with excellent levels of chemo- and position selectivity.

Key words

C–H bond activation - arylation - ruthenium catalysis - hetarenes - aryl halides

Publication History

Received: 14 April 2021

Accepted: 30 April 2021

Accepted Manuscript online:
30 April 2021

Article published online:
10 June 2021

• References and Notes

• 1a Rej S, Ano Y, Chatani N. Chem. Rev. 2020; 120: 1788
• 1b Ackermann L. Acc. Chem. Res. 2020; 53: 84
• 1c Khake SM, Chatani N. Trends Chem. 2019; 1: 524
• 1d Gandeepan P, Müller T, Zell D, Cera G, Warratz S, Ackermann L. Chem. Rev. 2019; 119: 2192
• 1e Wang C.-S, Dixneuf PH, Soulé JF. Chem. Rev. 2018; 118: 7532
• 1f Chu JC. K, Rovis T. Angew. Chem. Int. Ed. 2018; 57: 62
• 1g Park Y, Kim Y, Chang S. Chem. Rev. 2017; 117: 9247
• 1h Hartwig JF, Larsen MA. ACS Cent. Sci. 2016; 2: 281
• 1i Colby DA, Tsai AS, Bergman RG, Ellman JA. Acc. Chem. Res. 2012; 45: 814
• 2a Friis SD, Johansson MJ, Ackermann L. Nat. Chem. 2020; 12: 511
• 2b Wang W, Lorion MM, Shah J, Kapdi AR, Ackermann L. Angew. Chem. Int. Ed. 2018; 57: 14700
• 2c Jbara M, Maity SK, Brik A. Angew. Chem. Int. Ed. 2017; 56: 10644
• 2d Noisier AF. M, Brimble MA. Chem. Rev. 2014; 114: 8775
• 3a Moir M, Danon JJ, Reekie TA, Kassiou M. Expert Opin. Drug Discovery 2019; 14: 1137
• 3b Caro-Diaz EJ. E, Urbano M, Buzard DJ, Jones RM. Bioorg. Med. Chem. Lett. 2016; 26: 5378
• 3c Cernak T, Dykstra KD, Tyagarajan S, Vachal P, Krska SW. Chem. Soc. Rev. 2016; 45: 546
• 4a Bura T, Blaskovits JT, Leclerc M. J. Am. Chem. Soc. 2016; 138: 10056
• 4b Schipper DJ, Fagnou K. Chem. Mater. 2011; 23: 1594
• 5 Lutter FH, Grokenberger L, Perego LA, Broggini D, Lemaire S, Wagschal S, Knochel P. Nat. Commun. 2020; 11: 4443
• 6 On November 16, 2020, the prices of Pt, Rh, Ir, Pd, and Ru were 915, 14700, 1660, 2365, and 270 US$ per troy oz, respectively; http://www.platinum.matthey.com/prices/price-charts

For selected reviews on ruthenium-catalyzed C–H activations, see:
• 7a Leitch JA, Frost CG. Chem. Soc. Rev. 2017; 46: 7145
• 7b Li B, Dixneuf PH. Chem. Soc. Rev. 2013; 42: 5744
• 7c Ackermann L, Vicente R. Top. Curr. Chem. 2010; 292: 211

For selected examples, see:
• 7d Sagadevan A, Greaney M. Angew. Chem. Int. Ed. 2019; 58: 9826
• 7e Koseki Y, Kitazawa K, Miyake M, Kochi T, Kakiuchi F. J. Org. Chem. 2017; 82: 6503
• 7f Biafora A, Krause T, Hackenberger D, Belitz F, Gooßen LJ. Angew. Chem. Int. Ed. 2016; 55: 14752
• 7g Huang L, Weix DJ. Org. Lett. 2016; 18: 5432
• 7h Li B, Darcel C, Dixneuf PH. ChemCatChem 2014; 6: 127
• 7i Chinnagolla RK, Jeganmohan M. Chem. Commun. 2014; 50: 2442
• 7j Aihara Y, Chatani N. Chem. Sci. 2013; 4: 664
• 7k Dastbaravardeh N, Schnürch M, Mihovilovic MD. Org. Lett. 2012; 14: 1930
• 7l Ferrer Flegeau E, Bruneau C, Dixneuf PH, Jutand A. J. Am. Chem. Soc. 2011; 133: 10161
• 7m Arockiam PB, Fischmeister C, Bruneau C, Dixneuf PH. Angew. Chem. Int. Ed. 2010; 49: 6629
• 7n Oi S, Aizawa E, Ogino Y, Inoue Y. J. Org. Chem. 2005; 70: 3113

For representative examples of C–H activations by ruthenium(II) catalysis from our laboratories, see:
• 8a Korvorapun K, Moselage M, Struwe J, Rogge T, Messinis AM, Ackermann L. Angew. Chem. Int. Ed. 2020; 59: 18795
• 8b Rogge T, Ackermann L. Angew. Chem. Int. Ed. 2019; 58: 15640
• 8c Li J, Korvorapun K, De Sarkar S, Rogge T, Burns DJ, Warratz S, Ackermann L. Nat. Commun. 2017; 8: 15430
• 8d Schischko A, Ren H, Kaplaneris N, Ackermann L. Angew. Chem. Int. Ed. 2017; 56: 1576
• 8e Ackermann L, Vicente R, Potukuchi HK, Pirovano V. Org. Lett. 2010; 12: 5032
• 8f Ackermann L, Jeyachandran R, Potukuchi HK, Novák P, Büttner L. Org. Lett. 2010; 12: 2056
• 8g Ackermann L, Born R, Vicente R. ChemSusChem 2009; 2: 546
• 8h Ackermann L, Althammer A, Born R. Angew. Chem. Int. Ed. 2006; 45: 2619
• 8i Ackermann L. Org. Lett. 2005; 7: 3123
• 9 For a review on C–H activations on triazoles, see: Ackermann L, Potukuchi HK. Org. Biomol. Chem. 2010; 8: 4503
• 10 For detailed information, see the Supporting Information.
• 11a Korvorapun K, Struwe J, Kuniyil R, Zangarelli A, Casnati A, Waeterschoot M, Ackermann L. Angew. Chem. Int. Ed. 2020; 59: 18103
• 11b Korvorapun K, Kuniyil R, Ackermann L. ACS Catal. 2020; 10: 435
• 11c Simonetti M, Cannas DM, Just-Baringo X, Vitorica-Yrezabal IJ, Larrosa I. Nat. Chem. 2018; 10: 724
• 11d Simonetti M, Perry GJ, Cambeiro XC, Juliá-Hernández F, Arokianathar JN, Larrosa I. J. Am. Chem. Soc. 2016; 138: 3596
• 12 The mass balance was largely accounted for by the unreacted starting material 1, whereas only minor amounts of the corresponding desilylated triazole were observed.
• 13 4-{5-Chloro-2-[4-(trimethylsilyl)-1H-1,2,3-triazol-1-yl]phenyl}-6-methoxypyrimidine (3a) Under an atmosphere of N₂, a Schlenk tube was charged with triazole 1a (0.30 mmol, 1.00 equiv), 2-chloro-6-methoxypyrimidine (2; 0.45 mmol, 1.5 equiv), [Ru(O₂CMes)₂(p-cymene)] (8.4 mg, 15 μmol, 5.0 mol %), tris[4-(trifluoromethyl)phenyl]phosphine (L12; 7.0 mg, 15 μmol, 5.0 mol %), and K₂CO₃ (82.9 mg, 0.60 mmol, 2.00 equiv). PhMe (1.2 mL) was added and the mixture was stirred at 120 °C for 21 h then cooled to r.t. H₂O (10 mL) was added and the mixture was extracted with EtOAc (3 × 25 mL), washed with brine (25 mL), dried (Na₂SO₄), and concentrated in vacuo. The residue was purified by column chromatography [silica gel, hexane–EtOAc (5:1)] to give a yellow solid; yield: 53.6 mg (50%); mp 87–89 °C. IR (ATR): 1584, 1500, 1468, 1202, 1032, 838, 823, 758, 632, 417 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 8.70 (d, J = 1.0 Hz, 1 H), 7.82 (d, J = 2.2 Hz, 1 H), 7.58 (dd, J = 8.5, 2.2 Hz, 1 H), 7.51 (d, J = 8.1 Hz, 2 H), 6.19 (d, J = 1.1 Hz, 1 H), 3.91 (s, 3 H), 0.29 (s, 9 H). ¹³C NMR (75 MHz, CDCl₃): δ = 170.1 (CH), 161.9 (CH), 158.5 (C_q), 147.2 (CH); 136.2 (CH), 135.8 (CH), 133.9 (CH), 131.2 (C_q), 130.9 (C_q), 130.7 (C_q), 128.2 (C_q), 107.3 (C_q), 54.2 (CH₃), –1.1 (CH₃). MS (ESI): m/z (%) = 741 [2M + Na]⁺ (85), 559 (8), 382 [M + Na]⁺ (49), 360 [M + H]⁺ (100), 332 (16). HRMS (ESI): m/z [M + H]⁺ calcd for C₁₆H₁₉ ³⁵ClN₅OSi: 360.1042; found: 360.1028.
• 14 Ackermann L, Novák P, Vicente R, Pirovano V, Potukuchi HK. Synthesis 2010; 2245