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

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.