Regioselective Access to 3-Aryl-1-aminoisoquinolines via Nickel(I)-Catalyzed C–C and C–N Cascade Coupling Reactions from the Substituted 2-(Cyanomethyl)benzonitriles

Abstract

A novel and regioselective Ni(I) catalyzed C-C and C-N cascade coupling reactions has been developed. The cascade furnishes atom-economic access to 40 3-aryl-1-aminoisoquinolines. The regioselectivity of C(sp)-cyano group over C(sp)-cyano group was revealed and supported by mechanism studies as well as the preliminary density functional theory (DFT) calculations.

Design and Synthesis of New Quinoline Linked to Pyranotriazolopyrimidines Conjugates as Novel Targets to Discover Promising Anti-SARS-COV-2

“…In the compounds 4c and 4f, mentioned above, the cyanomethyl moiety made them valuable key precursors for the formation of several heterocyclic compounds 38,[41][42][43] and aroused our interest to explore them in order to obtain the desired hybrid compounds 5 and 6. In this context, and according of some previous work, 25,[44][45][46] we reacted compound 4c (Ar=Ph) with three salicylic arylaldehydes under reflux of ethanol in the presence of piperidine for 12 h leading to the new pyranotriazolopyrimidine-chromen conjugates 5a-c In the last few years, the condensation reactions of Knoevenagel have been considered a chosen path for the preparation of highly diverse molecules.…”

Nickel‐Catalyzed Cascade Reactions

“…Regioselective unprecedented C−C and C−N bond forming atom‐economic cascade coupling reaction was developed using nickel(I) catalyst to furnish 3‐aryl‐1‐aminoisoquinoline derivatives [26] . 2‐(Cyanoalkyl)arylnitrile 24 was involved in this cascade coupling reaction with arylboronic acid 10 in presence of 5 mol% Ni(acac) 2 , 5 mol% ligand (L 6 ), 20 mol% Cs 2 CO 3 in toluene at 110 °C for 6 h and provided 39–94 % desired coupled product 25 (Scheme 8).…”

“…Regioselective unprecedented CÀ C and CÀ N bond forming atom-economic cascade coupling reaction was developed using nickel(I) catalyst to furnish 3-aryl-1-aminoisoquinoline derivatives. [26] 2-(Cyanoalkyl)arylnitrile 24 was involved in this cascade coupling reaction with arylboronic acid 10 in presence of 5 mol% Ni(acac) 2 , 5 mol% ligand (L 6 ), 20 mol% Cs 2 CO 3 in toluene at 110°C for 6 h and provided 39-94 % desired coupled product 25 (Scheme 8). To get better yield of product, authors investigated the substrate scope for aryl boronic acid by substituting it with electron withdrawing group (F, Br, Cl, CF 3 , COMe), electron donating group (Me, Et, i Pr), heterocyclic ring (thiophene), naphthyl, acetal group and notably, among all substituents, boronic acid with electron donating substituents afforded better yields compared to others.…”

Nickel-catalyzed multicomponent reaction of dinitriles and hydrazine hydrochlorides with boronic acids: access to 1,3-diaryl-1H-pyrazol-5-amines and 4,5-dihydropyridazin-3(2H)-ones

“…Nickel, as a 3d transition metal, featuring abundance, inexpensiveness, and low toxicity, has exhibited excellent performance in catalytic reactions. 11 However, examples of nickel-catalyzed nitrile insertion reactions have been limited, 12–15 and there have been no reported examples about the synthesis of multi-substituted pyrazoles and dihydropyridazin-3(2 H )-one skeletons. Motivated by our continued endeavour in nitrile chemistry, 16 we herein report the first example of nickel-catalyzed three component reaction of commercially available malononitrile and butanedinitrile as reactants for the assembly of 1,3-diaryl-1 H -pyrazol-5-amines and 4,5-dihydropyridazin-3(2 H )-ones straightforwardly via an addition, condensation, and annulation sequence of boronic acids and hydrazine hydrochlorides (Scheme 1, eqn (e)).…”