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Yakugaku Zasshi. 2010 Jul;130(7):925-36.

Construction of indole- and isoquinoline-fused nitrogen-containing heterocycles through copper-catalyzed multi-component reaction.

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  • 1Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshidashimoadachi-cho, Sakyo-ku, Kyoto, Japan. yusukebe0108@f01.mbox.media.kyoto-u.ac.jp

Abstract

A copper-catalyzed synthesis of 2-(aminomethyl)indole through domino three-component coupling-cyclization has been developed. This reaction proceeds through Mannich-type coupling of 2-ethynylanilines, aldehydes, and secondary amines, followed by hydroamination. This indole formation was applicable to the synthesis of 4-methylene-2,3,4,9-tetrahyro-1H-pyrido[3,4-b]indoles and 5,6,7,8-tetrahydrobenzo[e]indolo[2,3-c]azepines via palladium-catalyzed C-H functionalization at the 3-position of indole. A combination of the three-component indole formation with nucleophilic cyclization promoted by t-BuOK or MsOH provides an effective access to beta-carboline scaffolds. Indole-fused 1,4-diazepines were also synthesized through deprotection/N-arylation at the nitrogen atom of indole by one-pot addition of MeONa after the formation of 2-(aminomethyl)indoles. In relation to the three-component indole formation, a novel four-component synthesis of isoquinolines has been developed. This isoquinoline formation includes Mannich-type reaction of 2-ethynylbenzaldehyde with (HCHO)(n) and secondary amine, imine formation with t-BuNH(2), isoquinoline formation, and elimination of t-butyl group to directly afford 3-(aminomethyl)isoquinolines in good yields. By the use of an alkane diamine instead of t-BuNH(2), fused 3-(aminomethyl)isoquinoline derivatives were obtained by cascade cyclization and oxidation.

PMID:
20606372
[PubMed - indexed for MEDLINE]
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