2-Aryl-4-chloro-3-iodoquinolines as Substrates for the Synthesis of 2,3-diaryl-4-methoxyquinolines

Abstract

Sequential functionalisation of 2-aryl-4-chloro-3-iodoquinolines via palladium-catalysed cross-coupling with phenylboronic acid followed by displacement of the 4-chloro atom from the resulting 2,3-diaryl-4-chloroquinolines with methoxide ion yielded 2,3-diaryl-4-methoxyquinolines. The latter were also prepared via Suzuki-Miyaura crosscoupling of 2-aryl-3-iodo-4-methoxyquinolines with phenylboronic acid. Demethylation of the methoxy compounds (BBr 3 ) gave the 2,3-diaryl-4(1H)-quinolinones.

Regioselective alkynylation of 2-aryl-4-chloro-3-iodoquinolines and subsequent arylation or amination of the 2-aryl-3-(alkynyl)-4-chloroquinolines

“…The observed selectivity is complementary to our previously reported results of Suzuki coupling of 2-aryl-3-iodo-4-(chloro/methoxy)quinolines with phenylboronic acid, which proceeded with C-3 regioselectivity. 1 We attribute the selectivity in both cases to the greater reactivity of the aryleiodide bond toward oxidative addition with palladium relative to the activated Csp 2 eCl bond.…”

“…During our research on the development of novel 2,3,4-trisubstituted quinoline derivatives with potential biological activity, 1 we became interested in the synthesis of alkynylated and alkenylated quinolines based on the 2-aryl-4-chloro-3-iodoquinoline framework. The aryl and alkynyl or alkenyl moieties are widely distributed in quinoline derivatives that serve as potent inhibitors of tyrosine kinase PDGF-RTK, 2 anti-retroviral agents 3 or LTD 4 receptor antagonists, 4 respectively.…”

ChemInform Abstract: Synthesis of 2‐Arylquinolin‐4(1H)‐ones and Their Transformation to N‐Alkylated and O‐Alkylated Derivatives

“…The C3 unsubstituted 2-aryl-4-chloroquinolines were also prepared by reaction of Vilsmeier reagent with 2 0 -azidochalcones, which are prepared in turn from the corresponding 2 0 -amonichalcones by diazotization followed by treatment with NaN 3 [68]. The 4-chloroquinolines 74 are then reacted with alkoxides or phenoxide ions to Scheme 19 [69,70]. This approach, which takes advantage of the ease of displacement of 4chlorine atom by nucleophiles has recently been used for the synthesis of 2,3-disubstituted 4-alkoxyquinoline derivatives (R 0 ¼ Me) that cannot be easily prepared otherwise.…”

“…This approach, which takes advantage of the ease of displacement of 4chlorine atom by nucleophiles has recently been used for the synthesis of 2,3-disubstituted 4-alkoxyquinoline derivatives (R 0 ¼ Me) that cannot be easily prepared otherwise. Series of 2-aryl-3-bromo/iodo-4-methoxyqui-nolines were prepared this way from the corresponding 2-aryl-4-chloro-3-halogenoquinolines [50,51,70]. This indirect approach has also been adapted to involve the use of organometalic reagents in the synthesis of 2,3-disubstituted 4-alkoxyquinolines.…”

“…The results of sequential functionalization of 2-aryl-4chloro-3-iodoquinolines 73 (X ¼ I) via palladium-catalyzed cross-coupling with phenylboronic acid followed by displacement of the 4-chloro atom from the resulting 2,3-diaryl-4-chloroquinolines 78 with methoxide ion to yield 2,3-diaryl-4-methoxyquinolines 79 have recently been described (Scheme 28). Compounds 79 were also prepared via Suzuki-Miyaura cross-coupling of 2-aryl-3iodo-4-methoxyquinolines 74 (R 0 ¼ Me, X ¼ I) with phenylboronic acid [70]. Demethylation of the methoxy compounds 79 with BBr 3 in CH 2 Cl 2 gave the 2,3-diaryl-4(1H)-quinolinones 80.…”