Halogenated Quinolines as Substrates for the Palladium‐Catalyzed Cross‐Coupling Reactions to Afford Substituted Quinolines

Abstract

View this article online at wileyonlinelibrary.com.The use of palladium complexes in catalyzing the cross-coupling of halogenated quinolines with various organometalic reagents has led to the development of radically new methods of synthesizing novel substituted quinoline derivatives. The focus of this review is on the application of the following palladium-catalyzed reactions of halogenated quinolines with organometalic reagents to afford substituted quinoline derivatives: Kumada, Stille, Negishi, Sonogashira, Suzuki, Heck, and Hiyama cross-coupling reactions. Scheme 4. Palladium-catalyzed coupling of the 4-bromoquinoline derivatives with zinc cyanide. Reagents and conditions: (i) Zn(CN) 2 , Pd(PPh 3 ) 4 , DMF, 80°C; (ii) Pyr·HBr, 200°C. Scheme 3. Palladium-catalyzed Negishi cross-coupling of quinolyl zinc iodides with organoiodides. Reagents and conditions: (i) Zn, DMA; (ii) Pd(dba) 2 , P(o-furyl) 3 , THF, room temperature or heat (for 13c, e, and f).4 M. Scheme 8. Successive Negishi cross-coupling of 2,6-dibromoquinoline with organozinc reagents. Reagents and conditions: (i) Pd(OAc) 2 , P(o-furyl) 3 , PhMe/DMA; (ii) [ 14 C]-MeZnI; NiCl 2 (dppp); THF. Scheme 9. Palladium-phosphinous acid-catalyzed alkynylation of 4-chloroquinoline. Reagents and conditions: (i) POPd, TBAB, NaOH, CuI, H 2 O, 5 h. Scheme 10. One-pot palladium/CuI-catalyzed dialkynylation of 2,4-dichloroquinoline. Reagents and conditions: (i) Pd/C, PPh 3 , CuI, NEt 3 , water, 80-85°C. 6 M.

Synthesis of Benzofuroquinolines via Phosphine‐Free Direct Arylation of 4‐Phenoxyquinolines in Air

“…Thus, the quinoline motif is considered a privileged biological scaffold, utilised by synthetic chemists to build molecular complexity, and ultimately improve biological activity. As a versatile heterocycle, it displays reactivity similar to that of other aromatic (pyridine/benzene) analogues, and thus can undergo a wide range of synthetic transformations , …”

A Green, Solvent-Free One-Pot Synthesis of Disubstituted Quinolines via A3-Coupling Using 1 Mol% FeCl3

“…used the Suzuki cross-coupling reaction and coupled 4-bromo-6-hydroxy-2-(substituted phenyl) quinoline 24 with phenylboronic acid and Ph(PP3)4 as a catalyst as well as sodium carbonate in dimethoxyethane to produce 6-hydroxy-2-(substituted phenyl)4-phenylquinoline 25 (Scheme 11). [24], [46] …”

“…[46] Kumada cross-coupling reactions are noted to proceed better at room temperature with quinoline derivatives, due to the soft nature of the palladium metal. [46] Bonnet et. al.…”

New Aryl Derivatives of Quinolinedione and Related Heterocyclic Compounds

“…The surge to employ halogenated quinolines as intermediates in metal‐catalyzed C–C bond formation for construction of complex molecules such as natural products, pharmaceuticals, and material science motivated investigating facile reaction protocol for functionalization of structurally related halogenated quinoline‐5,8‐dione . Quinoline‐5,8‐dione is an active component in various antimalaria, antimicrobial, anagelsic, cardiovascular, anticancer, and anti‐inflammatory drugs .…”