Knolker carbazole synthesis

Indole Ring Synthesis From Natural Products to Drug Discovery, First Edition. Gordon W. Gribble. 2016 John Wiley Sons, Ltd. Published 2016 by John Wiley Sons, Ltd. 

Demetalation of 4 with trimethylamine N-oxide yields car-bazole 5. Methylation gives carbazomycin A (1) [12]. In addition to carbazoles, Kndiker and his students applied this iron-mediated chemistry to the preparation of dihydroindoles [13, 14], (anhydrolycotine), tetrahydroindoles [15], dihydrocarbazoles [16], perhydroacenaphihenes [17], and azaspiroannelated ring systans [18-21], Several shorter accounts of Kndlker s carbazole syntheses [22-25] and the overall utility of tricarbonyl(Tl -diene)iron complexes in organic synthesis are available [26-32], 

The intermolecular nature of this rearrangement was confirmed by a crossover experiment (Schane 4, equations 1,2) [2,43], 

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

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

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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