Synlett
DOI: 10.1055/a-1495-6994
cluster
Late-Stage Functionalization

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

Torben Rogge
a  Institut für Organische und Biomolekulare Chemie, Georg-August-Universität Göttingen, Tammannstraße 2, 37077 Göttingen, Germany
,
Thomas Müller
a  Institut für Organische und Biomolekulare Chemie, Georg-August-Universität Göttingen, Tammannstraße 2, 37077 Göttingen, Germany
,
Hendrik Simon
a  Institut für Organische und Biomolekulare Chemie, Georg-August-Universität Göttingen, Tammannstraße 2, 37077 Göttingen, Germany
,
Xiaoyan Hou
a  Institut für Organische und Biomolekulare Chemie, Georg-August-Universität Göttingen, Tammannstraße 2, 37077 Göttingen, Germany
,
Simon Wagschal
b  Discovery Product Development and Supply, Janssen Pharmaceutica, Hochstrasse 201, 8200 Schaffhausen, Switzerland
,
Diego Broggini
b  Discovery Product Development and Supply, Janssen Pharmaceutica, Hochstrasse 201, 8200 Schaffhausen, Switzerland
,
a  Institut für Organische und Biomolekulare Chemie, Georg-August-Universität Göttingen, Tammannstraße 2, 37077 Göttingen, Germany
c  Wöhler Research Institute for Sustainable Chemistry, Georg-August-Universität Göttingen, Tammannstraße 2, 37077 Göttingen, Germany
› Author Affiliations
Generous support by the DFG (SPP1807 and Gottfried-Wilhelm-Leibniz award to L.A.) and by Janssen Pharmaceutica is gratefully acknowledged.


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.

Supporting Information



Publication History

Received: 14 April 2021

Accepted: 30 April 2021

Publication Date:
30 April 2021 (online)

© 2021. Thieme. All rights reserved

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
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  • 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 (Cq), 147.2 (CH); 136.2 (CH), 135.8 (CH), 133.9 (CH), 131.2 (Cq), 130.9 (Cq), 130.7 (Cq), 128.2 (Cq), 107.3 (Cq), 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