Quinolines, transition-metal-catalyzed

The Suzuki reaction has been successfully used to introduce new C - C bonds into 2-pyridones [75,83,84]. The use of microwave irradiation in transition-metal-catalyzed transformations is reported to decrease reaction times [52]. Still, there is, to our knowledge, only one example where a microwave-assisted Suzuki reaction has been performed on a quinolin-2(lH)-one or any other 2-pyridone containing heterocycle. Glasnov et al. described a Suzuki reaction of 4-chloro-quinolin-2(lff)-one with phenylboronic acid in presence of a palladium-catalyst under microwave irradiation (Scheme 13) [53]. After screening different conditions to improve the conversion and isolated yield of the desired aryl substituted quinolin-2( lff)-one 47, they found that a combination of palladium acetate and triphenylphosphine as catalyst (0.5 mol %), a 3 1 mixture of 1,2-dimethoxyethane (DME) and water as solvent, triethyl-amine as base, and irradiation for 30 min at 150 °C gave the best result. Crucial for the reaction was the temperature and the amount of water in the... 

Transition metal catalyzed hetero-annulation provides a useful and convenient tool for the construction of N-heterocycles [1]. Quinolines are of special interest in that they display attractive applications in pharmaceuticals and are synthetic building blocks [2, 3]. Catalytic processes employing palladium [4—6], rhodium [7-9], ruthenium [10-14], and iron [15] have been studied and developed to synthesize quinoline skeletons. There are five common methods used to prepare substituted quinolines the Skraup reaction [16], the Doebner-Von Miller reaction [17], the Conrad-Limpach reaction [18], the Friedlaender reaction [19, 20], and the Pfitz-inger reaction [21, 22]. All five of the reactions require environmentally unfriendly acids or bases, high temperatures, or harsh conditions. Quinoline yields are usually low due to numerous side reactions. Even though much work has been done to find catalytic routes to quinolines, the use of non-precious metals remains an active area of research. 

Scheme 3.56 Transition-metal-catalyzed synthesis of quinolines.

Gabriele et al. reported a transition-metal-catalyzed pyridine ring formation in 2007 [95]. Substituted quinolines 196 were synthesized efficiently by copper-catalyzed 6-endo-dig cyclization and dehydration of alkynylanilines 195 (Scheme 19.50). The reaction of silylated alkynes (R" = TMS) can also be catalyzed by Pdl2/KI to give quinolines 196a by a cyclodehydration-desilylation sequence. When the palladium-catalyzed reaction was carried out in the presence of CO and MeOH under oxidative conditions, the alkynes 195 were converted selectively into quinoline-3-carboxylic esters 197 in good yields. Quite interestingly, under nonoxidative... 

The scope of various pyridine derivatives with 1-hexene was examined with L45c-Sc/[Ph3C][B(C6F5)4] as the catalyst (Table 5.8). The asymmetric alkylation of 2-Me, 2-Et, 2- Pr, 2- Bu, and 2-phenyl-substituted pyridines 188 could also be achieved similarly in high yields (83-94%) and enantioselectivity (up to 94 6 er) (entries 1-5). Notably, the C—H bond activation reaction occurred selectively at the pyridine unit rather than at the phenyl group in the case of 2-phenylpyridine, which is in contrast with the reactions catalyzed by late transition metal complexes. The iodo, bromo, and chloro substituents in the picoline substrates are well compatible (entries 6-8). No alkylation reaction was observed with unsubstituted pyridine or quinoline, probably due to the poisoning effect of the N atom of pyridine to the metal center. 

---