Ligand-Free Palladium-Catalyzed Cyanation of Aryl Halides

Abstract

[reaction: see text] A practical, ligand-free cyanation of aryl bromides that utilizes as little as 0.1 mol % Pd(OAc)(2) in combination with a nontoxic cyanide source, M(4)[Fe(CN)(6)] (M = K, Na), is described. The reactions are performed in DMAC at 120 degrees C and provide the corresponding aryl nitrile in 83-96% yield, typically in less than 5 h. TON values of up to 7100 were attained.

Increasing the Scope of Palladium‐Catalyzed Cyanations of Aryl Chlorides

“…Among the tested solvents NMP gave comparable results to the standard solvent DMAc (Table 1, entries [13][14][15][16]. Although the use of potassium hexacyanoferrate(II) hydrate was found to be advantageous in some cases, [11,13] in this model reaction a major decrease of the yield occurred (Table 1, entry 19).…”

“…Although the use of potassium hexacyanoferrate(II) hydrate was found to be advantageous in some cases, [11,13] in this model reaction a major decrease of the yield occurred (Table 1, entry 19). Moreover, potassium hexacyanoferrateA C H T U N G T R E N N U N G (III) was tested, but also with low success (Table 1, entry 20).…”

Palladium‐Catalyzed Enantioselective Domino Heck–Cyanation Sequence: Development and Application to the Total Synthesis of Esermethole and Physostigmine

“…[12] To prevent catalyst deactivation, a variety of cyanide sources, such as alkali cyanide, zinc cyanide, acetone cyanohydrine, and trimethylsilyl cyanide, in combination with different solvents, have been proposed to fine-tune the cyanide concentration. [13] Recently Beller et al, [14] and subsequently Weissman et al [15] have demonstrated that potassium ferro(ii)cyanide (4) is an excellent cyanide source for the palladium-catalyzed cyanation of aryl halides. Following these observations, an intramolecular Heck-cyanation sequence involving a palladium catalyst was investigated by using o-iodoanilide 5 a as the test substrate with 4 as the terminating agent.…”

Synthesis of ortho-Functionalized 4-Aminomethylpyridazines as Substrate-Like Semicarbazide-Sensitive Amine Oxidase Inhibitors

“…13) Reaction of 4 with pyrrolidine or morpho-line gave the known 4-chloro-5-cycloaminopyridazinones 5a 14) and 5b, 13) respectively. Attempts to directly replace the 4-chloro substituent in compounds of type 5 with a cyano function by palladium-catalyzed cyanation 15) failed, so we decided to introduce the requisite carbon side chain at position C-4 by an electrophilic substitution reaction, after reductive removal of the halogen. Thus, catalytic transfer hydrogenation of 5a, b with ammonium formate/palladium gave the known 5-cycloaminopyridazinones 6a 16) and 6b, 13) respectively.…”