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 Pd-2(dba)(3)CHCl3/9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene-catalyzed reactions of the corresponding dibromobiphenyl compounds and methoxyamine. 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.