Carbazoles Knolker carbazole synthesis

Scheme 4 Pathway of Knolker Carbazole Synthesis and Crossover Experiment...

Utilizing previous chanistry of iron-complexed cyclohexadienylium cations, Knolker and colleagues have developed an extraordinarily versatile carbazole synthesis. 

Scheme 2 Knolker Palladium-Catalyzed Carbazole Synthesis...

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]. 

In other miscellaneous indole alkaloid syntheses. Joule reported formal syntheses of the makaluvamines <97JOC568> while Lown has developed a new synthesis of the pyrroloquinone nucleus of these alkaloids <97SC2103>. Edstrom reported the synthesis of a fully functionalized 7-aminoaziridinomitosene <97T4549>, and two new approaches to the duocarmycins were reported <97JOC8868,97TL7207>. Finally, Knolker has utilized his iron-mediated construction of carbazoles in the first. synthesis of the antibiotic carbazomycins C and D <97JCS(P1)349>, as well as other carbazole natural products. 

H. Knolker, and K. Reddy, Isolation and synthesis of biologically active carbazole alkaloids. Chem. Rev., 102 (2002) 4303-427. 

A number of studies on the palladium(n)-mediated oxidative cyclization of aniUno-quinones later appeared. Some of the compounds produced via this protocol are depicted in Figure 9.4. Bittner et al. [37b] and Furukawa and coworkers [37c] both described the application of the intramolecular cyclization chemistry toward the synthesis of analogues of the carbazole-l,4-quinone alkaloids. Furukawa and coworkers [37c] also reported the synthesis of murrayaquinone A (79) using this chemistry. Knolker and O Sullivan [37d,e] later demonstrated the utility of the palladium(ll)-mediated cycUzation in the synthesis of 83, which was initially anticipated to be a prekinamycin analogue precursor. In all... 

Since that initial report, a number of cyclizations on similar compounds have been described (Scheme 9.19). Akermark et al. [47a] illustrated that fcrt-butyl hydroperoxide can be used as a stoichiometric reoxidant in these reactions in their syntheses of murrayaquinone A (79) and other structural analogues. Knolker et al. [47c] demonstrated that the Pd(OAc)2/Cu(OAc)2 oxidation system can be utilized to access carbazole-l,4-quinone 121 in good yield, which was used as an intermediate in the synthesis of carbazoquinocin C. In 1999, Akermark and coworkers [47d] reported an intriguing example of an intramolecular oxidative Heck reaction of aniUnoquinone species 122 using molecular oxygen as the sole stoichiometric oxidant, affording 123 in 89% yield. 

An exceedingly versatile oxidative cyclization route to carbazoles was described by Knolker beginning in 1989 with a synthesis of carbazomycin A [1], This excellent chemistry and myriad applications to naturally occurring carbazoles is discussed in several reviews [2-11], The overall route is illustrated in Scheme 1 for a synthesis of carbazomycin A (1)... 

K.K. Gruner and H.-J. Knolker (2011) Carbazoles and acridines, in Heterocycles in Natural Product Synthesis, first ed. (eds K.C. Majumdar and S.K. Chattopadhyay), WUey-VCH Verlag GmbH Co. KGaA, pp. 341—376. 

Knolker, H., and M. Bauermeister The Total Synthesis of Carbazole Antibiotic... 

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