Palladium-Catalyzed Three-Component Cascade Reaction of Nitriles: Synthesis of 2-Arylquinoline-4-carboxylates

Abstract

A new method for converting easy availability starting materials 2-(2-oxoindolin-3-yl)acetonitrile, arylboronic acids, and alcohols into 2-arylquinoline-4-carboxylates is reported. The procedure involves a three-component addition/ring expansion/ esterification reaction in the presence of Pd(II) catalyst with high functional group tolerance under mild conditions. In addition, the photophysical properties of the resulting product were investigated and exhibited excellent polarity-sensitive fluorescence properties and AIE property.T he great importance of the quinoline core was present in medicinal chemistry, organic synthesis, and materials science. 1 Among these quinoline derivatives, compounds based on the 2-arylquinoline-4-carboxylates have attracted increasing attention due to their significant pharmacological properties (Figure 1). Their biological activities are widely used as antiproliferative drug, antidiabetic, PIM-1 kinase inhibitor, anti-inflammatory drug, P450 protein inhibitor and others. 2 The Pfitzinger reaction is a traditional strategy for the construction of 2-arylquinoline-4-carboxylate core. 3 However, this method used to complete the assembly of desired products involves vigorous conditions (strong bases, high temperature) and tedious procedures. Elegant achievements have been limited.Recently, a variety of methods to synthesize 2-arylquinoline-4-carboxylates have been developed. The advances could be divided into four classes: (1) cyclization of N-arylimines with propiolates or acrylates (Scheme 1a); 4 (2) radical reaction of

Metal-catalyzed reactions of organic nitriles and boronic acids to access diverse functionality

“…98 Recently, in 2021, an effective catalytic path to construct 2-arylquinoline-4-carboxylate ( 144 ) via a Pd( ii )-catalyzed addition/ring expansion/esterification reaction of 2-(2-oxoindolin-3-yl)acetonitrile ( 143 ), arylboronic acids, and alcohols was reported by Chen, Chen and Li's group (Scheme 72). 99 This strategy is successfully applied to access organic fluorescent carbazole-containing 2-arylquinoline-4-carboxylates, which showed excellent polarity-sensitive fluorescence properties and aggregation-induced emission (AIE) behaviour. Based on the experimental observations, a plausible mechanism for this cascade approach is proposed (Scheme 72).…”

“…Based on the experimental observations, a plausible mechanism for this cascade approach is proposed (Scheme 72). 99 Initially, transmetalation occurs with arylboronic acid and a Pd( ii ) catalyst to form an arylpalladium species ( A ), which is coordinated to the cyano group of 2-(2-oxoindolin-3-yl)acetonitrile to generate complex ( B ). After that, insertion of aryl to the cyano group generates an imine palladium complex ( C ), which is hydrolyzed to a dicarbonyl compound ( D ).…”

Visible-Light-Mediated Solvent-Switched Photosensitizer-Free Synthesis of Polyfunctionalized Quinolines and Pyridines

“…9 In 2021, Chen et al demonstrated a Pd(II)-catalyzed three-component reaction of nitriles for the synthesis of 2arylquinoline-4-carboxylates involving addition and ring expansion, followed by esterification [Scheme 1(ii)]. 10 In 2017, a Cu(I)-catalyzed [2 + 2 + 2] synthesis of multisubstituted pyridines was developed by Chen's group, which was initiated via alkenylation of nitriles with vinyliodonium salts [Scheme 1(iii)]. 11 A similar [2 + 2 + 2] cycloaddition of α,ω-diynes with nitriles using Ir(I)-catalyzed is reported by the Takeuchi group to access pyridines [Scheme 1(iv)].…”

“…In 2019, Chen and Shao’s group reported a Pd­(II)-catalyzed addition of arylboronic acids with 2-aminostyryl nitriles to access 2-arylquinolines [Scheme (i)] . In 2021, Chen et al demonstrated a Pd­(II)-catalyzed three-component reaction of nitriles for the synthesis of 2-arylquinoline-4-carboxylates involving addition and ring expansion, followed by esterification [Scheme (ii)] . In 2017, a Cu­(I)-catalyzed [2 + 2 + 2] synthesis of multisubstituted pyridines was developed by Chen’s group, which was initiated via alkenylation of nitriles with vinyliodonium salts [Scheme (iii)] .…”

Base Metal-Controlled Chemodivergent Cyclization of Propargylamines for the Atom-Economic Synthesis of Nitrogen Heterocycles

“…It is well-known that the Pfitzinger reaction is a traditional method for building a 2-arylquinoline-4-carboxylate core with strong bases and a high temperature . In recent years, a variety of novel synthetic approaches for preparing 2-substitued quinoline-4-carboxylate derivatives have been developed (Scheme ), including (a) cyclization of N -arylimines with ketonic acids, acrylates, or propiolates, (b) radical reaction of vinyl azides and α-carbonyl benzyl bromides, (c) [2+1+3] cyclization of 1,3-dicarbonyl compounds with aryl methyl ketones and arylamines, and (d) a three-component cascade reaction of 2-(2-oxoindolin-3-yl)­acetonitrile, arylboronic acids, and alcohols …”