Palladium-Catalyzed Copper-Free Sonogashira Coupling of 2-Bromoarylcarbonyls: Synthesis of Isobenzofurans via One-Pot Reductive Cyclization

Abstract

Palladium-catalyzed copper-free Sonogashira coupling of 2-bromocarbonyls is presented. This method afforded the 2-alkynylaryl carbonyls, useful synthons for the accomplishment of many carbocyclic and heterocyclic motifs. Significantly, the strategy was extended to the one-pot synthesis of isobenzofurans via reduction followed by intramolecular 5-exo-dig cyclization.

Recent Expedition inPd‐CatalyzedSonogashira Coupling and Related Processes†

“…2‐Alkynylarylcarbonyls were used to synthesize heterocycles via a reduction followed by an intramolecular exo‐dig or endo‐dig cyclization (Scheme 8b). [ 49 ] A similar reaction protocol was used in the intermolecular Sonogashira coupling and intramolecular 5‐ exo ‐ dig cycloisomerization cascade reaction to obtain benzofuran derivatives. [ 50 ] The Pd(OAc) 2 / Xanthpos catalyst system was further used in the on‐DNA Sonogashira coupling with HP‐ArOFs in 2019.…”

Environmentally friendly Nafion-catalyzed synthesis of 3-substituted isoquinoline by using hexamethyldisilazane as a nitrogen source under microwave irradiation

“…43, 153.85, 149.28, 131.46 (2×), 130.01, 128.75, 128.43 (2×), 122.46, 121.15, 114.34, 109.10, 94.73, 84.91, 68.72, 56.19, 30.88, 19.07, 13.75. 4-Fluoro-2-( phenylethynyl)benzaldehyde (2i). 29 Yield = 90% (202 mg); brown solid; mp = 36-37 °C; HRMS (FAB, M + + H) calcd for C 15 H 10 FO 225.0716, found 225.0719; 1 H NMR (500 MHz, CDCl 3 ): δ 10.57 (s, 1H), 7.98 (dd, J = 6.0, 8.5 Hz, 1H), 7. 60-7.53 (m, 2H), 7.44-7.37 (m, 3H), 7.32 (dd, J = 2.5, 9.0…”

“…38-7.31 (m, 2H), 7.28-7.23 (m, 1H), 7.13-7.06 (m, 1H); 13 C NMR (125 MHz, CDCl 3 ): δ 191. 29,162.35 (d,J = 245.75 Hz),135.90,133.74,133.26,130.10 (d,J = 8.625 Hz),128.91,127.54 (d,J = 2.75 Hz),127.40,126.14,124.10 (d,J = 9.5 Hz),118.39 (d,J = 22.75 Hz),116.38 (d,J = 21.0 Hz),94.77 (d,J = 3.25 Hz),85.71. 2-((4-Chlorophenyl)ethynyl)benzaldehyde (2t). 30 Yield = 85% (205 mg); yellow solid; mp = 95-96 °C; HRMS (FAB, M + + H) calcd for C 15 H 10 ClO 241.5413, found 241.5411; 1 H NMR (500 MHz, CDCl 3 ): δ 10.60 (s, 1H), 7.94 (d, J = 8.0 Hz, 1H), 7.62 (d,J = 8.0 Hz,1H),7.58 (t,J = 7.5 Hz,1H),3H),7.35 (d,J = 8.5 Hz,2H); 13 C NMR (125 MHz, CDCl 3 ): δ 191.…”

Room-Temperature, Copper-Free, and Amine-Free Sonogashira Reaction in a Green Solvent: Synthesis of Tetraalkynylated Anthracenes and In Vitro Assessment of Their Cytotoxic Potentials

“…However, the presence of copper salts can sometimes have deleterious effects on catalysis, which include but are not limited to participation in the Glasser homocoupling of two terminal alkynes to form dialkynes, ,, inhibition of the activity of the Pd catalyst, and oxidation of unsaturated Pd(0) species to halide-bridged dinuclear Pd­(I) complexes that accelerate polymerization of the alkyne. Rightly, a lot of research emphasis is devoted to the development of copper-free and preferably amine-free Sonogashira catalytic systems. ,, …”

“…Rightly, a lot of research emphasis is devoted to the development of copper-free and preferably amine-free Sonogashira catalytic systems. 12 , 15 , 17 …”