No abstract

D-Ring substituted 11H-indoloA C H T U N G T R E N N U N G [3,2-c]quinolines (4) have been prepared via auto-tandem consecutive intermolecular Buchwald-Hartwig reaction and intramolecular palladium-catalyzed arylation on 4-chloroquinoline (1) with N-unsubstituted 2-chloroanilines (2). The reported 11H-indoloA C H T U N G T R E N N U N G [3,2-c]quinolines (4) represent the first examples in which tandem catalysis has been used to construct N-unsubstituted carbolines.Keywords: amination; C À H activation; malaria; palladium; tandem catalysis IntroductionIn 2003 our research group published a communication which described a new method for the synthesis of 11H-indoloA C H T U N G T R E N N U N G [3,2-c]quinoline (4a) starting from commercially available 4-chloroquinoline (1) and 2-chloroA C H T U N G T R E N N U N G aniline (2a) (Scheme 1).[1] The methodology consists of two consecutive palladium-catalyzed reactions: a selective Buchwald-Hartwig reaction (chemoselective oxidative addition) followed by an intramolecular arylation involving C À H activation. [2,3] The latter reaction is interesting in itself as published examples on intramolecular Pd-catalyzed arylations of electron-deficient heteroaromatics are scarce in comparison with electron-rich heteroarenes.[3c] Selective N-5 methylation of the obtained 11H-indoloA C H T U N G T R E N N U N G [3,2-c]quinoline (4a) yielded the antiplasmodial natural product isocryptolepine (5-methyl-5H-indoloA C H T U N G T R E N N U N G [3,2-c]quinoline) (5a) (Scheme 1).[4] The increasing resistance of parasites of the genus Plasmodium to well known drugs like chloroquine and mefloquine prompted us to investigate more closely the biological Scheme 1. Synthesis of 4a via consecutive palladium-catalyzed reactions.

No abstract

Alkaloids Alkaloids U 0600Synthesis of Isocryptolepine via a Pd-Catalyzed "Amination-Arylation" Approach. -A Pd-catalyzed Buchwald-Hartwig amination of 4-chloroquinoline (I) with 2-chloroaniline followed by Pd-catalyzed intramolecular arylation and regioselective N-methylation results in a short synthesis of the title compound (VI). -(JONCKERS, T. H. M.; MAES*, B. U. W.; LEMIERE, G. L. F.; ROMBOUTS, G.; PIETERS, L.; HAEMERS, A.; DOMMISSE, R. A.; Synlett 2003, 5, 615-618; Dep. Chem., Univ. Antwerp, B-2020 Antwerpen, Belg.; Eng.) -Mais 30-227

Isocryptolepine (cryptosanguinolentine) has been synthesized in three steps via a new approach starting from commercially available 4-chloroquinoline and 2-chloroaniline. The new methodology consists of two consecutive palladium-catalyzed reactions; a selective Buchwald-Hartwig amination followed by an intramolecular arylation reaction.