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Review
. 2025 Dec 4;15(56):47863-47912.
doi: 10.1039/d5ra06627a. eCollection 2025 Dec 3.

State-of-the-art transition metal-catalyzed approaches to quinoline frameworks via multicomponent reactions

Mosstafa Kazemi  1 , Ghada Al Assi  2 , Ramin Javahershenas  3 , Rekha M M  4 , Shaker Al-Hasnaawei  5   6 , Subhashree Ray  7 , Amrita Pal  8 , Renu Sharma  9
Affiliations
Review

State-of-the-art transition metal-catalyzed approaches to quinoline frameworks via multicomponent reactions

Mosstafa Kazemi et al. RSC Adv. .

Abstract

Quinoline derivatives are vital nitrogen-containing heterocycles that are widely utilized in pharmaceuticals, agrochemicals, and materials science. Recent advancements have highlighted the effectiveness of multi-component reactions (MCRs) as efficient and versatile strategies for constructing these complex molecules, offering high atom economy, operational simplicity, and broad structural diversity. Transition metal catalysts such as palladium, copper, iron, and silver have been instrumental in optimizing quinoline synthesis via MCRs, significantly enhancing the reaction efficiency, selectivity, and scope. These catalysts facilitate key transformations, including cyclization, C-C and C-N bond formation, and oxidative coupling under mild conditions. This review offers a comprehensive overview of the state-of-the-art transition metal-catalyzed MCR approaches for quinoline construction, emphasizing the reaction mechanisms, catalytic performance, and developments in sustainable methodologies. Additionally, it discusses future directions for catalyst design and expands on the synthetic potential of these methodologies to meet emerging scientific and industrial needs.

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Conflict of interest statement

The authors affirm that there are no conflicts of interest to disclose.

Figures

Fig. 1
Fig. 1. Advantages of transition metals for catalysis.
Fig. 2
Fig. 2. Several examples of bioactive quinoline derivatives.
Fig. 3
Fig. 3. Advantages of multicomponent reactions (MCRs) in heterocyclic synthesis.
Scheme 1
Scheme 1. Synthesis of multiply-substituted quinolines [catalysis by Cu(OTf)2].
Scheme 2
Scheme 2. Plausible mechanism for the synthesis of multiply-substituted quinolines [catalysis by Cu(OTf)2].
Scheme 3
Scheme 3. Synthesis of functionalized quinolines [catalysis by CuI].
Scheme 4
Scheme 4. Synthesis of functionalized quinolines [catalysis by CuI].
Scheme 5
Scheme 5. Plausible mechanism for the synthesis of functionalized quinolines [catalysis by CuI].
Scheme 6
Scheme 6. Synthesis of 2,4-disubstituted quinolines from alkynes [catalysis by Cu(OTf)2].
Scheme 7
Scheme 7. Synthesis of 2,4-disubstituted quinolines from ketones [catalysis by Cu(OTf)2].
Scheme 8
Scheme 8. Plausible mechanism for the synthesis of 2,4-disubstituted quinolines from alkynes [catalysis by Cu(OTf)2].
Scheme 9
Scheme 9. Plausible mechanism for the synthesis of 2,4-disubstituted quinolines from ketones [catalysis by Cu(OTf)2].
Scheme 10
Scheme 10. Synthesis of 2-arylquinolines [catalysis by CuCl2].
Scheme 11
Scheme 11. Plausible mechanism for the synthesis of 2-arylquinolines [catalysis by CuCl2].
Scheme 12
Scheme 12. Synthesis of 4-hydroxalkyl-quinolines [catalysis by CuCl/AuCl].
Scheme 13
Scheme 13. Plausible mechanism for the synthesis of 4-hydroxalkyl-quinolines [catalysis by CuCl/AuCl].
Scheme 14
Scheme 14. Synthesis of 2,3-diarylquinoline derivatives.
Scheme 15
Scheme 15. Plausible mechanism for the synthesis of 2,3-diarylquinoline derivatives.
Scheme 16
Scheme 16. Synthesis of 2,4-substituted quinolines [catalysis by CuFeO2 nanoparticles].
Scheme 17
Scheme 17. Plausible mechanism for the synthesis of 2,4-substituted quinolines [catalysis by CuFeO2 nanoparticles].
Scheme 18
Scheme 18. Synthesis of 4-aryl quinolines [catalysis by the FeCl3/K2S2O8 system].
Scheme 19
Scheme 19. Plausible mechanism for the synthesis of 4-aryl quinolines [catalysis by the FeCl3/K2S2O8 system].
Scheme 20
Scheme 20. Synthesis of 2-aryl quinolines [catalysis by FeCl3].
Scheme 21
Scheme 21. Plausible mechanism for the synthesis of 2-aryl quinolines [catalysis by FeCl3].
Scheme 22
Scheme 22. Synthesis of 2,4-disubstituted quinoline derivatives [catalysis by FeCl3].
Scheme 23
Scheme 23. Plausible mechanism for the synthesis of 2,4-disubstituted quinoline derivatives [catalysis by FeCl3].
Scheme 24
Scheme 24. Synthesis of highly substituted quinolines [catalysis by Ir(ppy)3].
Scheme 25
Scheme 25. Synthesis of highly substituted quinolines [catalysis by Ir(ppy)3].
Scheme 26
Scheme 26. Plausible mechanism for the synthesis of highly substituted quinolines [catalysis by Ir(ppy)3].
Scheme 27
Scheme 27. Synthesis of 2,3-difunctionalized quinolines [catalysis by Ir(ppy)3].
Scheme 28
Scheme 28. Plausible mechanism for the synthesis of 2,3-difunctionalized quinolines [catalysis by Ir(ppy)3].
Scheme 29
Scheme 29. Synthesis of 2,4-difunctionalized quinolines [catalysis by K5CoW12O40·3H2O].
Scheme 30
Scheme 30. Plausible mechanism for the synthesis of 2,4-difunctionalized quinolines [catalysis by K5CoW12O40·3H2O].
Scheme 31
Scheme 31. Synthesis of 4-phenyl quinolines [catalysis by Cp*Co(CO)I2].
Scheme 32
Scheme 32. Synthesis of 3,4-difunctionalized quinolines [catalysis by Cp*Co(CO)I2].
Scheme 33
Scheme 33. Plausible mechanism for the synthesis of 4-phenyl quinolines [catalysis by Cp*Co(CO)I2].
Scheme 34
Scheme 34. Synthesis of quinoline derivatives [catalysis by Cp*Co(CO)I2].
Scheme 35
Scheme 35. Plausible mechanism for the synthesis of quinoline derivatives [catalysis by Cp*Co(CO)I2].
Scheme 36
Scheme 36. Synthesis of poly-substituted quinolines [catalysis by Pd(CF3CO2)2].
Scheme 37
Scheme 37. Plausible mechanism for the synthesis of poly-substituted quinolines [catalysis by Pd(CF3CO2)2].
Scheme 38
Scheme 38. Synthesis of 3-substituted quinolines [catalysis by Sc(OTf)3].
Scheme 39
Scheme 39. Plausible mechanism for the synthesis of 3-substituted quinolines [catalysis by Sc(OTf)3].
Scheme 40
Scheme 40. Synthesis of polysubstituted quinolines [catalysis by AgOTf].
Scheme 41
Scheme 41. Plausible mechanism for the synthesis of polysubstituted quinolines [catalysis by AgOTf].
Scheme 42
Scheme 42. Synthesis of quinoline derivatives [catalysis by RuH2CO(PPh3)3/xantphos].
Scheme 43
Scheme 43. Plausible mechanism for the synthesis of quinoline derivatives [catalysis by RuH2CO(PPh3)3/xantphos].
Scheme 44
Scheme 44. Synthesis of 4-substituted quinolines [catalysis by Zn(OTf)2].
Scheme 45
Scheme 45. Plausible mechanism for the synthesis of 4-substituted quinolines [catalysis by Zn(OTf)2].
Scheme 46
Scheme 46. Synthesis of 2,4-diaryl quinolines [catalysis by MNPs@Cellulose/Zn-MOF].
Scheme 47
Scheme 47. Plausible mechanism for the synthesis of 2,4-diaryl quinolines [catalysis by MNPs@Cellulose/Zn-MOF].
Scheme 48
Scheme 48. Synthesis of substituted quinolines from dicarbonyls [catalysis by Cp2ZrCl2/CuO].
Scheme 49
Scheme 49. Synthesis of substituted quinolines from ketones [catalysis by Cp2ZrCl2/CuO].
Scheme 50
Scheme 50. Plausible mechanism for the synthesis of substituted quinolines from dicarbonyls [catalysis by Cp2ZrCl2/CuO].
Scheme 51
Scheme 51. Synthesis of 2,4-disubstituted quinolines [catalysis by MOF-5].
Scheme 52
Scheme 52. Plausible mechanism for the synthesis of 2,4-disubstituted quinolines [catalysis by MOF-5].
None
Mosstafa Kazemi
None
Ramin Javahershenas
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