A highly efficient methodology for the preparation of N-methoxycarbazoles and the total synthesis of 3,3'-[oxybis(methylene)]bis(9-methoxy-9H-carbazole)

Abstract

A convenient and highly efficient method is described for the synthesis of N-methoxycarbazole derivatives, including those with sterically demanding, benzannulated, or strongly electron-donating or -withdrawing substituents. Various N-methoxycarbazole derivatives were directly prepared in good-to-moderate yields by the Pd₂(dba)₃CHCl₃/9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene-catalyzed reactions of the corresponding dibromobiphenyl compounds and methoxya-mine. Based on this methodology, the first total synthesis of 3,3′-[oxybis(methylene)]bis(9-methoxy-9H-carbazole), an antimicrobial dimeric carbazole alkaloid previously isolated from the stem bark of Murraya koenigii, was achieved in 18% yield over seven steps from 1,2-dibromobenzene.

Graphical abstract

Keywords

N-methoxyl carbazole / dimeric N-methoxyl carbazole / alkaloid / total synthesis / double N-arylation of methoxyamine

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Acknowledgements

This work was supported by the Natural Science Foundation of Tianjin, China (No. 15JCYBJC20100).

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2020 Higher Education Press