Recent advances and prospects in the palladium-catalyzed cyanation of aryl halides

Abstract

Aryl nitriles are compounds with wide significance. They have made their own space in various sectors including pharmaceuticals, industries, natural product chemistry, and so on. Furthermore, they are also key intermediates in various transformations in organic chemistry. Transition metal-catalyzed cyanation reactions have proved to be a better replacement for the existing traditional synthetic strategies for aryl nitriles. Palladium is one of the most studied transition metals other than copper and nickel owing to its wide functional group compatibility and catalytic efficacy. There have been drastic developments in the field of palladium-catalyzed cyanation since its discovery in the 1973. This review summarizes the recent developments in the palladium-catalyzed cyanation of aryl halides and covers literature from 2012-2020.

Fig. 1. Pharmaceutically significant motifs containing nitriles.

Scheme 1. General reaction displaying the formation of aryl cyanides from haloarenes.

Scheme 2. Water-mediated synthesis of benzonitriles using polymer braced macrocyclic palladium complex.

Scheme 3. Synthesis of aryl cyanides from aryl chlorides.

Scheme 4. Synthesis of heteroaryl cyanides from heteroaryl halides.

Scheme 5. Palladium–zinc ferrite nanoparticles catalyzed synthesis of aryl cyanides.

Scheme 6. Synthesis of diverse benzonitriles using Pd-beta zeolite as the catalyst at 130 °C.

Scheme 7. Aryl halide cyanation employing organic solvents and water as the solvent media.

Scheme 8. Substrate scope studies towards the synthesis of various aryl cyanides.

Scheme 9. Palladium supported on zinc oxide nanoparticles-catalyzed cyanation of aryl bromides and chlorides.

Scheme 10. Investigations on cyanation of aryl halides catalyzed by CN-dimeric ortho-palladated complex via microwave and conventional heating.

Scheme 11. IL@SBA-15-Pd catalyzed cyanation of aryl halides and its substrate scope studies.

Scheme 12. Optimized reaction condition for the synthesis of various aryl cyanides catalyzed by Pd(OAc)₂.

Scheme 13. Cyanation of haloarenes with K₄[Fe(CN)₆] in the presence of Pd@CuFe₂O₄.

Scheme 14. One pot mono-cyanation of various aryl halides using N-heterocyclic carbene and palladium.

Scheme 15. Double cyanation of substituted aryl bromides catalyzed by palladium acetate and N-heterocyclic carbene.

Scheme 16. Pd NPs on C@Fe₃O₄ catalyzed synthesis of diversely substituted haloarenes and heterohaloarenes.

Scheme 17. Possible mechanistic trajectory for the cyanation reaction. [This figure has been reproduced from ref. 51 with permission from AMERICAN CHEMICAL SOCIETY, copyright 2015].

Scheme 18. Investigations on the synthesis of mono, di and tri-cyanoarenes using Pd@CC1^r/Pd@CC2^r.

Scheme 19. Polymeric ligand PA^I mediated synthesis of different aryl bromides and chlorides.

Scheme 20. Synthesis of ortho-mono/bis-C–H-amination and ipso-C–I-cyanation of aryl iodides.

Scheme 21. Substrate scope for the cyanation of aryl halides by CuI/Pd(ii)-AOFs.

Scheme 22. Synthesis of aryl and heteroaryl cyanides from chloroarenes and bromoarenes using TABP.

Scheme 23. Biogenetically synthesized palladium nanoparticles catalyzed formation of various benzonitriles.

Scheme 24. Aryl halide cyanation catalyzed by Fe₃O₄@PMDP/Pd.

Scheme 25. Substrate scope investigations of cyanation of aryl halides using Pd/PDA with and without TBAB.

Scheme 26. K₄[Fe(CN)₆] mediated Pd@CS-biguanidine catalyzed synthesis of various cyanobenzenes.

Scheme 27. Plausible mechanism for the formation of aryl cyanides. [This figure has been reproduced from ref. 60 with permission from ELSEVIER, copyright 2020].

Scheme 28. (1) Mono-cyanation reactions catalyzed by Pd-CD-PU-NS. (2) Synthesized bis-cyanated products by the same protocol.

Scheme 29. Letrozole synthesis involving Pd-CD-PU-NS catalyzed cyanation as one of the steps.

Scheme 30. Formation of mono and dicyanoarenes via catalysis by Pd/coral reef nanocomposite.

Scheme 31. One-pot approach towards the synthesis of various aryl cyanides using K₄[Fe(CN)₆].

Scheme 32. Synthesis of different aryl cyanide motifs from various aryl halides using Fe₃O₄/chitosan/pumice hybrid beads.

Scheme 33. Pd NPs@CAP catalyzed formation of various benzonitriles-a substrate scope analysis.

Scheme 34. Reaction of various aryl halides with CuSCN to generate the corresponding aryl cyanides.

Scheme 35. Suggested mechanistic route towards the product synthesis. [This figure has been reproduced from ref. 67 with permission from AMERICAN CHEMICAL SOCIETY, copyright 2013].

Scheme 36. t-BuXPhos mediated cyanation of aryl halides catalyzed by Zn(CN)₂.

Scheme 37. Formation of reverse transcriptase inhibitor-lersivirine inspired from the above protocol.

Scheme 38. Functional group tolerance of different aryl halides in the presence of benzyl cyanide.

Scheme 39. The plausible trajectory through which the reaction proceeds. [This figure has been reproduced from ref. 69 with permission from ROYAL SOCIETY OF CHEMISTRY, copyright 2020].

Scheme 40. Ethyl cyanoacetate mediated palladium catalyzed synthesis of benzonitriles.

Scheme 41. Substrate scope studies of the cyanation of aryl iodides and bromides using formamide.

Scheme 42. Functional group tolerance of various aryl halides towards cyanation and their yield range.

Scheme 43. Acetone cyanohydrin-mediated formation of diverse aryl cyanides.

Scheme 44. Cyanation reaction of different iodoarenes assisted by hexamethylenetetramine.

Scheme 45. Synthetic pathway for the cyanation reaction carried out by HMTA. [This figure has been reproduced from ref. 75 with permission from AMERICAN CHEMICAL SOCIETY, copyright 2017].

Scheme 46. Synthesis of various benzonitriles from aryl iodides and bromides catalyzed by Pd(OAc)₂.

Scheme 47. Wide range of substrate scope towards the synthesis of various cyanobenzenes in the presence of cyanuric chloride.

Mohan Neetha

C. M. A. Afsina

Thaipparambil Aneeja

Gopinathan Anilkumar