Transition metal-catalyzed cyanation and isocyanation of aryl halides and sulfonates

Abstract

The mildest cyanation has been developed for aryl halides and sulfonates with environmental friendly cyanating source: K₄[Fe(CN)₆]3H₂O. In the presence of highly effective Pd/CMPhos catalyst, cyanation of aryl chlorides proceeds at 70 °C in general, which is the mildest reaction temperature achieved so far for this process. Moreover, sterically hindered non-activated ortho-ortho-disubstituted electrophile was also a feasible coupling partner in cyanation. In addition, palladium-catalyzed cyanation of aryl bromides was also achieved general application of aryl halides in cyanation. The reactions were completed at 50°C under mixed solvents (water/MeCN = 1:1). This result is the mildest temperature published so far for palladium-catalyzed aryl bromides cyanation. In order to further explore cyanation, the coupling of aryl mesylates was investigated. Interestingly, the use of water as the solvent or a co-solvent was found to be essential. Moreover, this system was also applicable to the cyanation of other aryl and alkenyl tosylates. The one-pot cyanationamination sequence demonstrated the suitability of the cyanation of aryl chlorides and tosylates for the introduction of a nitrile group and manipulation of a further functional group in a synthetic pathway without isolation of the initial nitrile-substituted intermediates. These palladium catalyst systems tolerated common functional-groups: nitriles, esters, ketos, aldehydes, free amines, and heterocyclic groups are found compatible. Lastly, a palladium-catalyzed decarboxylative coupling of potassium cyanoacetate with aryl bromides and chlorides was also described. The reaction conditions featured the absence of additional strong inorganic bases and provided ester functional group tolerance. With Pd(dba)₂ and XPhos ligand as the catalyst system, α-diaryl nitriles could be obtained in good yields.