Microwave-Assisted and Yb(OTf)3-Promoted One-Pot Multicomponent Synthesis of Substituted Quinolines in Ionic Liquid

Abstract

A straightforward and efficient method has been developed for the synthesis of quinolines by Yb(OTf) 3 catalyzed threecomponent reaction of aldehydes, alkynes, and amines under microwave irradiation in ionic liquid. A series of 2,4-disubstituted quinolines was synthesized in excellent yield (69-93%) under mild reaction condition and the catalyst was recycled for four cycles.

The Beneficial Sinergy of MW Irradiation and Ionic Liquids in Catalysis of Organic Reactions

“…Substituted quinolines could be prepared in IL solvent by a MCR with a Lewis acid catalyst, with MW heating [147]. Different ILs and different metal triflates were used to optimize the reaction conditions that were successively used for the reaction with different substrates.…”

Microwave Reactors: A Brief Review on Its Fundamental Aspects and Applications

“…11) A straightforward and efficient Yb(OTf) 3 catalyzed three-component reaction of aldehydes, alkynes and amines under microwave irradiation in an ionic liquid has been developed. A number of 2,4-disubstituted quinolines have been synthesized in excellent yield (69% -93%) under mild reaction condition [72] and the catalyst is reused up to four times. 12) 3,3′-Br 2 -BINOL has been shown to catalyze the enantioselective asymmetric propargylation of ketones using allenyldioxoborolane as nucleophile, in absence of solvent and under microwave irradiation to afford homopropargylic alcohols in good yields (60% -98%) and high enantiomeric ratios (3:1 -99:1) [73].…”

Synthesis of Highly Functionalized 4‐Aminoquinolines

“…[2a,4] 4-Amino-substituted quinolines are of particular pharmaceutical interest, [4a,6] and over the years,s everal synthetic routes to these compounds have been explored. [7] Them ain drawback of al ot of the existing quinoline syntheses is the difficulty of functionalization at the C2 and C3 positions.Herein, we present the synthesis of adiverse array of new, highly substituted 4-aminoquinolines from sulfonyl ynamides and electrophilically activated amides.I nc ontrast to other methods,t his approach allows for substitution at the C2 and C3 as well as at the C5 to C8 positions.F urthermore,t he installed 4-amino group is accessible after deprotection, thus providing further points of diversity (Scheme 1).Quinolines can be made in several different ways.M ore recently developed approaches for the formation of quinolines are based on the conversion of 2-alkynyl arylazides into substituted 4-acetoxyquinolines under gold catalysis, [8] onepot InCl 3 /SiO 2 catalyzed reactions towards 4-methylquinolines, [9] and the use of ring-closing metathesis to access 4-hydroxy-or 4-methylquinolines.[10] 4-Phenylquinolines are accessible by aY b(OTf) 3 catalyzed multicomponent reaction [11] or by a" green" solvent-free one-pot process between 2-aminoaryl ketones and aryl acetylenes.[12] 4-Aminoquinolines can be prepared by the reduction of quinoline-4-phenylhydrazine, [13] by hypobromite oxidation of 2,3-dimethylquinoline-4-carboxyamides, [14] via a4 -chloroquinoline precursor, [6a] by rearrangements of pyrazolium-3-carboxylates via pyrazol-3-ylidene intermediates, [15] by reacting 2-(trifluoromethyl)-4H-3,1-benzoxazinones with ynamines, [16] or by an aerobic oxidative Pd-catalyzed imidoylative coupling with double C À Ha ctivation.[17] These approaches usually allow for some degree of functionalization on the quinoline core,and with the 4-chloro precursor strategy,4-aminoquinolines with aw ide range of functional groups at the C5 to C8 positions have been synthesized and found to be promising in antimalarial assays.[18] However,a ccessing both the C2, C3 and the C5 to C8 positions has remained achallenge thus far.Thek ey to our synthesis of 4-aminoquinolines is the activation of the amides with ac ombination of triflic anhydride [19] (Tf 2 O) and 2-chloropyridine (2-ClPy), ap rocedure used by Movassaghi and co-workers to prepare aw ide …”

“…Quinolines can be made in several different ways.M ore recently developed approaches for the formation of quinolines are based on the conversion of 2-alkynyl arylazides into substituted 4-acetoxyquinolines under gold catalysis, [8] onepot InCl 3 /SiO 2 catalyzed reactions towards 4-methylquinolines, [9] and the use of ring-closing metathesis to access 4-hydroxy-or 4-methylquinolines. [10] 4-Phenylquinolines are accessible by aY b(OTf) 3 catalyzed multicomponent reaction [11] or by a" green" solvent-free one-pot process between 2-aminoaryl ketones and aryl acetylenes. [12] 4-Aminoquinolines can be prepared by the reduction of quinoline-4phenylhydrazine, [13] by hypobromite oxidation of 2,3-dimethylquinoline-4-carboxyamides, [14] via a4 -chloroquinoline precursor, [6a] by rearrangements of pyrazolium-3-carboxylates via pyrazol-3-ylidene intermediates, [15] by reacting 2-(trifluoromethyl)-4H-3,1-benzoxazinones with ynamines, [16] or by an aerobic oxidative Pd-catalyzed imidoylative coupling with double C À Ha ctivation.…”