Transition-Metal-Free Cross-Coupling of Aryl and N-Heteroaryl Cyanides with Benzylic Zinc Reagents

Abstract

Functionalized 4-benzylated pyridines can be efficiently prepared by a transition-metal-free cross-coupling between various benzylic zinc chlorides and substituted 4-cyanopyridines in THF/DMPU under microwave irradiation (40 °C, 0.5-1.5 h). Selective benzylations on polycyano-aromatics have also been achieved under these mild conditions. We also report a novel oxidative nucleophilic substitution of a hydrogen on 1,3-dicyanobenzene using benzylic zinc reagents.

A Versatile One‐Pot Access to Cyanoarenes from ortho‐ and para‐Quinones: Paving the Way for Cyanated Functional Materials

“…Considering the effort for the published syntheses of 9,10‐dicyanophenanthrene 17 , it becomes clear that a direct conversion of ortho ‐quinones to cyanoarenes is a valuable extension of the reaction scope of the presented one‐pot protocol.…”

“…As the nitrile represents a versatile functional group in synthetic chemistry, a large number of secondary products can be synthesized from appropriately substituted cyanoarenes. For 1,4‐dicyanobenzenes and 9,10‐dicyanoanthracenes, the known modifications include the preparation of the corresponding aldehydes, thioamides, various heterocyclic compounds, and nucleophilic benzylation by using readily available zinc reagents . Moreover, dicyanoarenes have been applied as ligands in π‐stacked metalloparacyclophanes…”

Recent Progress in Utilization of Functionalized Organometallic Reagents in Cross Coupling Reactions and Nucleophilic Additions

“…Quinio and Knochel et al 65 developed a novel nucleophilic benzylation of polycyano-aromatics and 4-cyanopyridines using various readily available benzylic zinc chlorides in THF/DMPU under microwave irradiation (40 °C, 0.5-1.5 h), providing polyfunctional pyridines and cyano-substituted aromatics (Scheme 63). Furthermore, a novel oxidative nucleophilic substitution of a hydrogen using 1,3-dicyanobenzene with benzylic zinc reagents also took place in this procedure.…”

Decyanative Cross‐Coupling of Cyanopyrimidines with O‐, S‐, and N‐Nucleophiles: A Route to Alkoxylpyrimidines, Aminopyrimidines and Alkylthiopyrimidines

“…However, because of the high dissociation energy of Ar–CN bonds (≈ 132.7 kcal mol –1 ) in comparison with Ar–X (X=Cl, Br, I) bonds (< 100 kcal mol –1 ), aryl nitriles have rarely been regarded as a suitable substrate to participate in cross‐coupling reactions . If the cyano group could be employed as the leaving group, Ar–CN would become an alternative substrate to Ar–X for the cross‐coupling reaction , . Since Miller first reported the synthesis of unsymmetrical biaryls via the cross‐coupling of aryl nitriles with Grignard reagents using a phosphine‐based Ni catalyst, continued attention has been paid to decyanative cross‐coupling reactions .…”