Carbazoles copper catalyzed synthesis

A rather unusual procedure has been published for the palladium- and copper-catalyzed synthesis of triarylamines, using an alkaline water-ethanol emulsion stabilized by cetyltrimethylammonium bromide [41]. Anyway, this method overcomes the problem in the synthesis of N-aryl carbazoles (Eq. 14), which are not accessible by the method developed by Hartwig and Buchwald [42],... 

The copper-catalyzed synthesis of carbazoles from 2-aminobiphenyls via intramolecular C-H amination also could be realized using Mn02 as terminal oxidant (Scheme 8.42). The picolinamide-based bidentate directing group which could be spontaneously removed after the coupling reaction was crucial for this reaction. This Cu(OAc)2 catalytic system could proceed smoothly under I(III)-free conditions. Moreover, a few of heteroatom-containing carbazole core r-systems could be contained easily under the mild Cu(0Ac)2/Mn02 catalytic conditions [80]. 

Scheme 8.42 Copper-catalyzed synthesis of carbazoles from 2-aminobiphenyls via intramolecular C-H amination using MnOj as terminal oxidant.

The intramolecular amine-halogen copper-promoted indohzation was applied to the synthesis of more-complex indoles (Scheme , equations 1 ) [58-61]. Other examples in this category of copper-catalyzed amination are syntheses of the carbazole alkaloids murrayaquinone-A and ( )-bis-murrayaquinone-A [62], 3-aryl p-carbolin-l-ones [63, 64], carbazoles from donble C-N cyclization [65], pyrrolo[2,3-c]... 

In this domino process, benzylamine was reacted with 2-halobenzamides through UUman-type coupling to yield the N-arylated intermediate 144 (Scheme 9.26). Then, a copper-catalyzed aerobic oxidation of 144 afforded the intermediate 145, which underwent an intramolecular nucleophilic addition of the amide to provide 146. Under the used reaction conditions, the intermediate 146 was oxidized to provide the desired products 147 in excellent yield. This protocol was also utilized by Fu et al. [80] by employing easily available a-amino adds instead of benzylamines to synthesize similar analogs. Very recently, the same method was applied for the synthesis of pyrimido[4,5-b]carbazoles by Nagarajan et al. [81]. 

Double N-arylation can also be conducted by using copper catalysts. In 2007, Martin, Li, and co-workers independently reported pyrrole synthesis via copper-catalyzed C—N bond formation between l,4-dihalo-l,3-dienes and amines [13]. They applied this methodology to carbazole synthesis (Scheme 23.9). In general, diiodobiaryl gave better results than dibromobiaryls. As a nitrogen source, carbamates and amides were investigated in their reports. 

A construction of the carbazole framework involving copper(ll)-catalyzed aryla-mine arylation and palladium(ll)-mediated oxidative cyclization has been reported by Menendez et al. (Scheme 41) [190, 191]. The diarylamines 95 were obtained by copper(ll) acetate-catalyzed N-arylation of arylamines 31 with phe-nyllead triacetate (183) using Barton s conditions [192]. Subsequent oxidative cyclization using palladium(ll) acetate under microwave irradiation afforded the carbazoles 32. This procedure was applied to the synthesis of murrayafoline A (188) [190]. 

Subsequently, these authors also used the palladium(ll)-catalyzed version with copper(ll) acetate as co-oxidant, originally reported by Knolker et al. [142-152], for the synthesis of murrayafoline A (188), 2-methoxy-3-methylcarba-zole (146), and glycozohdine (170) (Scheme 42), as well as some non-natural carbazoles [191]. 

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