Total synthesis of natural pyrano[3,2-a]carbazole alkaloids

Abstract

An efficient approach for the total synthesis of pyrano[3,2-a]carbazole alkaloids was reported, resulting in the synthesis of six natural pyrano[3,2-a]carbazole alkaloids, namely girinimbine (1), mukoenine C (2), koenimbine (3), koenigine (4), koenine (5), and koenidine (6). In the present study, the readily available 2-methyl-5-nitrophenol was employed as a starting material for the synthesis of aminochromenes. The intermediate diphenylamine was produced through the Buchwald-Hartwig coupling reaction, which ultimately facilitated the synthesis of pyrano[3,2-a]carbazole via the intramolecular palladium(II)-catalyzed oxidative cyclization of diphenylamine. In the palladium-catalyzed oxidative cyclization process, this approach successfully circumvents the Wacker oxidation by restricting the involvement of water, ultimately enabling the selective dehydrogenative oxidative cyclization of the C–C bond of the aryl ring. Consequently, this strategy simplifies the complexity of the reaction and reduces the synthesis steps.