2-Arylquinolines

AT-Arylquinolin-2(lff)-ones have been prepared in a four step process from commercially available coumarins, utilizing a Buchwald-Hartwig ami-... 

Later, different ethyl 4-hydroxy-2-arylquinoline-3-carboxylates were prepared by this route, by heating aryl(phenylamino)methylenemalonates in the melt at 150-160°C under reduced pressure (49JIC171). 

Akiyama et al. extended this reaction to alkynylimines for the preparation of quinoline derivatives [28]. Treatment of N-aryl(alkynyl)imines 99 with 20 mol% W (CO)5(thf) in THF at reflux followed by oxidative work-up using NMO gave 2-arylquinolines 100 in reasonable yield through electrocydization of the vinylidene intermediate (Scheme 5.31). 

In an application of the Suzuki process, 2-chloroquinoline (141) has been converted into the condensed heterocycle 197 (Scheme 58) (89JHC1589). Thus, metalation, trimethyl borate quench, and hydrolysis affords the stable 3-boronic acid 195 which, upon subjection to cross coupling with ortho-iodo aniline in the presence of Pd(0) catalyst and base, affords the 3-arylquinoline 196. Acid catalysis converts this material into the in-dolo[2,3-f ]quinoline (197) in 35% overall yield. 

Hewawasam, P. and Starrett, J. E. (Bristol-Myers Squibb) 3-Substituted-4-arylquinolin-2-one derivatives as potassium channel modulators, W00034244. 

Tetrahydroquinolones can be transformed also by (diacetoxyiodo)benzene 3 to the aromatic arylquinolines, a structure found in various alkaloids [101]. Depending on the reagent, it is possible to oxidize flavanones 50 either into flavones 51 or into rearranged isoflavones 52 [102, 103]. (Diacetoxyiodo)-benzene 3 or the polymer-supported reagent 18 were also efficient reagents for the oxidation of 1,4-dihydropyridines 53 to the corresponding pyridine derivatives 54, Scheme 23 [104]. 

Gopalsamy A, Pallai PV, Combinatorial synthesis of heterocycles solid phase synthesis of 2-arylquinoline-4-carboxylic acid derivatives, Tetrahedron Lett., 38 907-910, 1997. 

Nucleophilic ring-opening of benzoxazinones by enolates of arylacetic esters followed by deacylation of the amine group resulted in cyclization to the desired 3-arylquinolin-2-ones <03JOC4567>. 

A mild, highly efficient, scalable synthesis of 4-arylquinolin-2-ones from 2-aminobenzophenones was reported <03TL4271>. By reacting the starting material with lactones and two equivalents of LiHMDS, the desired compounds are formed in good to excellent yields. 

A route to 4-(l-alkenyl)isoquinolines and 4-alkyl-3-arylquinolines via palladium(II)-catalyzed cyclization, followed by olefination, was developed through many trials. Substrates were chosen for their ability to stabilize the Pd(II) intermediate, and to promote the Pd-catalyzed cyclization. An o-methoxy substituent on the aryl group was found to be necessary <03JOC980>. Forty-one examples are given. 

Although the presence of alkaloids in Lunasia amara Blanco has been long recognized and several bases were isolated and characterized during the first half of this century (Volume V, p. 316) the structures of only two had been elucidated by 1957 (Volume VII, p. 241) both of these being simple 2-arylquinoline derivatives (XXVII and XXVIII). Shortly... 

Alkoxy-2-arylquinolines 2-Aryl-l,2,3,4-tetrahydro-4-quinolones undergo dehydrogenation and O-methylation when treated with PhI(OTs)OH, HCIO, and HCjOMejj. 

Milbank JB, Knauer CS, Augelli-Szafran CE et al (2007) Rational design of 7-arylquinolines as non-competitive metabotropic glutamate receptor subtype 5 antagonists. Bioorg Med Chem Lett 17 4415-4418... 

The biosynthesis of 2-alkyl- and 2-arylquinoline alkaloids was investigated by Luckner and co-workers. For example, anthranilic acid was incorporated intact into 2-heptyl-4-hydroxyquinoline 339 in the microorganism Pseudomonas aeruginosa. Acetate and malonate are also precursors, and degradation experiments showed that the side chain was... 

The Ziegler reaction (see p 278) with organolithium compounds leads exclusively to 2-alkyl- or 2-arylquinolines. For instance, 20 is produced with -butyllithium. After hydrolysis, the primary adducts (e.g. 16) yield stable 1,2-dihydroquinolines (e.g. 17) which can be dehydrogenated by nitro compounds. It is obvious that control of the RLi addition occurs through coordination, because even 2-substituted quinolines (e.g. 18) yield mainly 2-addition products (e.g. 19). 

Some routes have been described which involve the formation of two C-C bonds in the same pot to produce quinolines and isoquinolines. For the production of 2-arylquinolines a Schiff base is reacted with an enol ether in presence of ytterbium(III) triflate. 2-Chloro-3-formylquinolines result from a practically simple process... 

Stille et al. completed the total synthesis of amphimedine (297) in eight steps and overall 21-23% yield (Scheme 33) (136). Their synthesis started with the readily available 4-quinolinone 298 (144), which was reacted with trifluoromethanesulfonic anhydride to give the triflate 299. Coupling of 299 with the organostannane 302 in the presence of Pd(PPhs)4 yielded the 4-arylquinoline 303, oxidation of which with ceric ammonium nitrate (CAN) or silver(II) oxide failed to produce any of the expected quinone. Thus,... 

Arylquinoline-4-carboxylic acids and derivatives were shown to possess a wide variety of biological effects as antimalarial, antimicrobial, antitumor, antioxidants and cardiovascular agents. In addition, other derivatives have recently been shown to be potent tachykinin NK3 receptor antagonist " or to exhibit analgesic activity. O ... 

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