Nickel Catalyzed Cross-Couplingand Amination Reactions of Aryl Nitriles

Abstract

Aryl nitriles have been found to participate in cross-coupling and amination reactions via nickel-catalyzed activation of the C-CN bond. With the development of these synthetically useful transformations, aryl nitriles can now be considered along with aryl halides and sulfonates as viable substrates for these types of reactions.

Suzuki–Miyaura and Related Cross‐Couplings in Aqueous Solvents Catalyzed by Di(2‐pyridyl)methylamine‐Palladium Dichloride Complexes

“…The compounds 4,5-diphenyl-2-methyl-3(2H)pyridazinone, [34] N,N-dimethyl(4-phenyl)aniline, [36] 2,6-dimethylbiphenyl, [37] have been previously reported.…”

Bis(trimethylphosphine)nickel Dichloride

“…The use of trimethylphosphine as a ligand is essential, as other phosphines such as Me 2 PPh, Et 3 P, MePPh 2 , Ph 3 P, Cy 3 P, and dppe provide much lower yields of cross-coupled products. Alkenyl and alkyl Grignard reagents modified with lithium tertbutoxide or lithium thiophenolate also undergo cross-coupling with a range of benzonitriles in the presence of substoichiometric (Me 3 P) 2 NiCl 2 (eqs 4-6). 2, 3 The combination of Ni(acac) 2 (5 mol %) and Me 3 P (10 mol %) is equally effective, whereas other precatalysts, such as (Et 3 P) 2 NiCl 2 , Ni(acac) 2 /1,3-bis(2,4,6-trimethylphenyl)imidazolium chloride or (t-Bu 3 P) 2 Pd, are ineffective.…”

“…4 However, the use of alkynylzinc reagents provides notable improvements (eqs 7-9). 4 In the presence of (Me 3 P) 2 NiCl 2 (10 mol %) in THF at reflux, a range of aromatic compounds containing electron-donating or electron-withdrawing groups undergo smooth alkynylation. Heteroaromatic nitriles also undergo the reaction.…”

“…Finally, this process appears to exhibit useful chemoselectivity; 4-chlorobenzonitrile reacts predominantly at the nitrile group, with only trace amounts of the dialkynylation product observed, and none of the monoalkynylation product resulting from cross-coupling at the chloride detected. + Ar = 4-pyridyl, 56% Ar = 3-pyridyl, 45% [using 5 mol % of (Me 3 P) 2 NiCl 2 ]…”

“…During a formal synthesis of the natural product salinosporamide A, (Me 3 P) 2 NiCl 2 (10 mol %) was found to be an effective precatalyst for a diethylzinc-mediated reductive aldol cyclization-lactonization reaction that was used to construct the γ-lactam (Scheme 1). 5 This reaction produces a mixture of two diastereomeric products, and proceeds presumably by initial reductive cyclization of the α,β-unsaturated amide onto the methyl ketone 6 to provide a diastereomeric mixture of zinc alkoxides, each of which then undergoes lactonization through attack onto the pendant ethyl ester.…”