Synlett, Table of Contents Synlett 2021; 32(05): 491-496DOI: 10.1055/s-0040-1707818 cluster The Power of Transition Metals: An Unending Well-Spring of New Reactivity © Georg Thieme Verlag Stuttgart · New York Sequentially Catalyzed Three-Component Masuda–Suzuki–Sonogashira Synthesis of Fluorescent 2-Alkynyl-4-(7-azaindol-3-yl)pyrimidines: Three Palladium-Catalyzed Processes in a One-Pot Fashion Daniel Drießen , Lukas Biesen , Thomas J. J. Müller ∗ Recommend Article Abstract All articles of this category Abstract The Masuda–Suzuki–Sonogashira sequence efficiently unites, in a one-pot fashion, a borylation, an arylation, and an alkynylation in the sense of a sequentially Pd-catalyzed three-component reaction to give fluorescent 2-alkynyl-4-(7-azaindol-3-yl) pyrimidines in yields of 24–83% (14 examples). Time-dependent density-functional theory calculations supported the electronic structure of the longest wavelength absorption bands, revealing that this novel consecutive three-component synthesis opens an efficient access to alkynyl meriolins, a novel class of potential inducers of apoptosis. Key words Key wordsarylation - alkynylation - borylation - fluorescence - multicomponent reaction - meriolins Full Text References References and Notes 1a Lessing T, Müller T. Appl. Sci. 2015; 5: 1803 1b Müller TJ. J. Top. Organomet. Chem. 2006; 19: 149 2 D’Souza DM, Müller TJ. J. Chem. Soc. Rev. 2007; 36: 1095 3a Baudoin O, Guénard D, Guéritte F. J. Org. Chem. 2000; 65: 9268 3b Baudoin O, Cesario M, Guénard D, Guéritte F. J. Org. Chem. 2002; 67: 1199 3c Penhoat M, Levacher V, Dupas G. J. Org. Chem. 2003; 68: 9517 3d Broutin PE, Čerňa I, Campaniello M, Leroux F, Colobert F. Org. Lett. 2004; 6: 4419 3e Abreu AS, Ferreira PM. T, Queiroz M.-JR. P, Ferreira IC. F. R, Calhelha RC, Estevinho LM. Eur. 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L.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Montgomery, J. A. Jr.; Peralta, J. E.; Ogliaro, F.; Bearpark, M.; Heyd, J. J.; Brothers, E.; Kudin, K. N.; Staroverov, V. N.; Kobayashi, R.; Normand, J.; Raghavachari, K.; Rendell, A.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.; Rega, N.; Millam, J. M.; Klene, M.; Knox, J. E.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Martin, R. L.; Morokuma, K.; Zakrzewski, V. G.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Dapprich, S.; Daniels, A. D.; Farkas, Ö.; Foresman, J. B.; Ortiz, J. V.; Cioslowski, J.; Fox, D. J. Gaussian 09, Gaussian, Inc., Wallingford, 2016. 12 Products 5a–m; General Procedure 7-azaindole 1a (398 mg, 1.00 mmol) and (Ph3P)4Pd (35.0 mg, 0.03 mmol) were placed in a dry screw-cap vessel equipped with a magnetic stirrer bar. The vessel was evacuated and refilled with argon three times, then anhyd 1,4-dioxane (5.00 mL) was added and the resulting mixture was degassed with argon for 10 min. Dry Et3N (1.40 mL, 10.0 mmol) and 4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.25 mL, 1.70 mmol) were successively added and the mixture was stirred in a preheated oil bath at 80 °C for 4 h then cooled to r.t. (water bath). Dry 1,2-dimethoxyethane (9.00 mL) and H2O (1.00 mL) were added, and the mixture was stirred at r.t. for 10 min. 2,4-Dichloropyrimidine (2; 149 mg, 1.00 mmol) and Cs2CO3 (823 mg, 2.50 mmol) were then added, and the mixture was stirred in a preheated oil bath at 80 °C for 18 h. When the Suzuki coupling was complete, the mixture was cooled to r.t. (water bath), and CuI (19.0 mg, 0.10 mmol) and the appropriate alkyne 4 (1.20 mmol) were added. The mixture was stirred at 45–80 °C for 18 h. When the Sonogashira coupling was complete (TLC), the mixture was cooled to r.t. (water bath), the solvents were removed in vacuo, and the residue was absorbed onto Celite. After purification by chromatography (silica gel, hexane–acetone), the product was sonicated in hexane–acetone (95:5) for further purification. The solvent was removed and the residue was dried in vacuo at 70 °C for 42 h. 1-[(4-Methylphenyl)sulfonyl]-3-[2-(phenylethynyl)pyrimidin-4-yl]-1H-pyrrolo[2,3-b]pyridine (5a) The final Sonogashira step was carried out at 80 °C for 18 h to give a yellow solid; yield: 310 mg (0.68 mmol, 68%); mp 200.3–202.7 °C; Rf = 0.48 (CH2Cl2–acetone, 6:4). IR (neat): 3379 (w), 3107 (w), 3090 (w), 3026 (w), 2918 (w), 2218 (w), 1593 (m), 1570 (s), 1555 (w), 1533 (s), 1491 (m), 1479 (w), 1425 (w), 1398 (s), 1381 (m), 1368 (s), 1335 (w), 1302 (m), 1262 (m), 1244 (m), 1186 (s), 1171 (s), 1155 (s), 1123 (w), 1075 (w), 1036 (m), 1017 (m), 999 (w), 961 (s), 918 (w), 883 (m), 866 (w), 849 (w), 837 (m), 822 (m), 802 (m), 775 (s), 756 (s), 732 (s), 675 (s), 654 (s), 633 (w) cm–1. 1H NMR (600 MHz, DMSO-d 6): δ = 2.35 (s, 3 H, CH3), 7.44–7.54 (m, 6 H, CHAr), 7.72 (d, 3 J HH = 6.7 Hz, 2 H, CHAr), 8.09 (d, 3 J HH = 8.5 Hz, 2 H, CHAr), 8.23 (d, 3 J HH = 5.4 Hz, 1 H, CHAr), 8.48 (dd, 3 J HH = 4.7 Hz, 4 J HH = 1.6 Hz, 1 H, CHAr), 8.85 (d, 3 J HH = 5.4 Hz, 1 H, CHAr), 8.88 (dd, 3 J HH = 8.0 Hz, 4 J HH = 1.6 Hz, 1 H, CHAr), 9.03 (s, 1 H, CHAr). 13C NMR (150 MHz, DMSO-d 6): δ = 21.1 (CH3), 86.2 (Cquat), 88.6 (Cquat), 115.5 (Cquat), 116.4 (CH), 119.8 (CH), 120.4 (Cquat), 120.5 (Cquat), 128.0 (CH), 129.0 (CH), 129.2 (CH), 130.1 (CH), 130.2 (CH), 131.7 (CH), 132.2 (CH), 134.0 (Cquat), 145.7 (CH), 146.2 (Cquat), 146.9 (Cquat), 152.0 (Cquat), 157.8 (CH), 159.8 (Cquat). EI MS: m/z (%) = 450 (21) [M+], 386 (100) [C21H14N4O2S+], 385 (36), 296 (11), 268 (12), 267 (19), 155 (13) [C7H7O2S+], 142 (14), 141 (12) [C9H5N2 +], 127 (11), 114 (14) [C9H6 +], 91 (90) [C7H7 +], 65 (14) [C5H5 +]. Anal. Calcd for C26H18N4O2S (450.5): C, 69.32; H, 4.03; N, 12.44; S, 7.12. Found: C, 69.11; H, 3.75; N, 12.19; S, 7.31. Supplementary Material Supplementary Material Supporting Information
