Synthetic Approach for Constructing the 1-Oxygenated Carbazole Core and Its Application to the Preparation of Natural Alkaloids

Abstract

An efficient synthetic approach for the construction of the 1-oxygenated carbazole core is described. The condensation of cyclohexane-1,2-diones with a series of anilines yielded the corresponding 2-anilinocyclohex-2-en-1-ones, followed by the one-pot aromatization/methylation process of the latter to provide N-aryl-2-methoxyanilines. A palladium(II)-catalyzed cyclization of these Naryl-2-methoxyanilines afforded the desired 1-methoxycarbazole frame in high overall yields. This protocol was implemented for the total synthesis of the naturally occurring glycozolicine and 6-methoxymurrayanine.

Palladium-Catalyzed Synthesis of Natural and Unnatural 2-, 5-, and 7-Oxygenated Carbazole Alkaloids from N-Arylcyclohexane Enaminones

“…However, the use of deactivated anilines, such as 3-nitro- and 4-nitroanilines, failed to provide the desired enaminones, thus limiting this procedure to anilines substituted with electron-donating groups. Applying our previous procedure for aromatization using Pd(OAc) 2 (30% mol) [37], derivatives 4a – b did not lead to the desired diarylamines 6a – b , but instead furnished the carbazole frame compounds 7a – b in good yields (Scheme 2). Similar results via Pd-mediated procedures have been reported for analogous substrates [1,38,39,40,41], which in turn have been transformed into the 4-oxygenated carbazoles [42].…”

“…The final cyclization step of diarylamines 5a – e was successfully carried out by following the protocol originally developed by Knölker and coworkers [40,56,57], later applied by others [28,29], and optimized in our syntheses of natural carbazoles [37,44]. Thus, the conversion of the series 5a – c and 5e into the carbazole derivatives 1h – k resulted in good yields (80%–92%) (Table 3).…”

“…We recently described a general synthetic approach for the construction of 1-methoxycarbazoles, including the naturally occurring alkaloid glycozolicine, which was accomplished with high overall yields through a three-step reaction sequence [37]. Based on this approach, we describe herein a new synthetic route for the preparation of 2-, 7-, and 2,7-oxygenated carbazoles 1 .…”

Upgrading furanic platforms to α-enaminones: tunable continuous flow hydrogenation of bio-based cyclopentenones

“…Over the years, different protocols have been developed for the synthesis of α-enaminones (Fig. 1b): (1) the conventional multistep synthesis from diketones; [11][12][13][14][15][16] (2) cyclic ketone oxidative coupling with anilines or O-benzoylhydroxylamines under mild conditions, including electrochemical methods; [17][18][19][20][21] more recently, (3) a threecomponent gold-catalysed coupling/cyclization reaction. 22 Despite all the progress, these elegant methods have some limitations, as they require pre-functionalised amination reagents (i.e.…”