2-Methoxy-3-methylcarbazole

The iron-mediated synthesis of 2-oxygenated carbazole alkaloids is limited and provides only a moderate yield (11%) for the oxidative cyclization to 2-methoxy-3-methylcarbazole using iodine in pyridine as the reagent [90]. Ferricenium hexafluorophosphate is the superior reagent for the iron-mediated arylamine cyclization leading to 3-oxygenated carbazoles (Scheme 12). Electrophilic substitution of the arylamines 16 with the complex salt 6a leads to the iron complexes 17. Oxidative cyclization of the complexes 17 with an excess of ferricenium hexafluorophosphate in the presence of sodium carbonate affords... 

Among the large number of carbazole alkaloids that have been isolated from M. koenigii are also many 2-oxygenated derivatives. In 1985, Bhattacharyya et al. isolated 2-methoxy-3-methylcarbazole (37) from the petroleum ether extract of the seeds of M. koenigii (55). The UV spectrum (Tmax 235,255,300, and 328 nm) and the IR... 

Formyl-3-methoxy-6-methylcarbazole (8-Formyl-6-methoxy-3-methylcarbazole) R H R =Me R = CHO... 

In 1992, Bhattacharyya et al. reported the isolation of glycozolicine (88) from the roots of G. pentaphylla, and originally assigned the structure as 5-methoxy-3-methylcarbazole (24). On their isolation of glycoborine (87) in 2001, Chakravarty et al. reassigned glycozolicine (88) as 8-methoxy-3-methylcarbazole (98) (Scheme 2.17). 

In 1990, Furukawa et al. described the isolation and structural elucidation of chrestifoline-A (192), -B (193), and -C (194) from the root bark of M. euchrestifolia. The chrestifolines contain l-methoxy-3-methylcarbazole [murrayafoline A (7)] as the common structural subunit, which is linked to the second carbazole via the methyl group at C-3. Chrestifoline-C (194) was isolated from nature in optically active form [aJo —5.6 (c 0.054, CHCI3). However, the absolute configuration is not known (161) (Schemes 2.45 and 2.46). 

The retrosynthetic analysis of the 2-oxygenated carbazole alkaloids, 2-methoxy-3-methylcarbazole (37) and mukonidine (54), based on an iron-mediated approach, led to the iron-complexed cation 602 and the arylamines 655 and 656 as precursors (Scheme 5.48). 

The retrosynthetic analysis of the 2-oxygenated carbazole alkaloids, 2-methoxy-3-methylcarbazole (37), O-methylmukonal (glycosinine) (38), 2-hydroxy-3-methylcar-bazole (52), and mukonal (53) based on the molybdenum-mediated approach led to the molybdenum-complexed cation (663) and 3-methoxy-4-methylaniline (655) as precursors (Scheme 5.51). The cationic molybdenum complex, dicarbonyl (ri -cyclohexadiene)(r -cyclopentadienyl)molybdenum hexafluorophosphate (663), required for the electrophilic substitution, was easily prepared quantitatively through known literature procedures (586,587). 

Electrophilic substitution of 3-methoxy-4-methylaniline (655) by the complex 663 leads to the molybdenum complex 664. Oxidative cyclization of complex 664 with concomitant aromatization using activated commercial manganese dioxide provides 2-methoxy-3-methylcarbazole (37) in 53% yield (560). In contrast, cyclization of the corresponding tricarbonyliron complex to 37 was achieved in a maximum yield of 11 % on a small scale using iodine in pyridine as the oxidizing agent (see Scheme 5.49). 

Electrophilic aromatic substitution of 3-methoxy-4-methylaniline (655) using the 2-methoxy-substituted iron complex salt 665, followed by oxidative cyclization with concomitant aromatization of the resulting iron complex salt 666, affords 2,7-dimethoxy-3-methylcarbazole (667). Oxidation of the carbazole 667 with DDQ... 

Furukawa et al. reported the total synthesis of murrayaquinone A (107) by a palladium(II)-mediated oxidative cyclization of the corresponding 2-arylamino-5-methyl-l,4-benzoquinones. 2-Anilino-5-methyl-l,4-benzoquinone (842) was prepared starting from 2-methyl-l,4-benzoquinone 841 and aniline 839, along with the regio-isomeric 2-anilino-6-methyl-l,4-benzoquinone (844). The oxidative cyclization of 2-anilino-5-methyl-l,4-benzoquinone (842) with stoichiometric amounts of palla-dium(ll) acetate provided murrayaquinone A (107) in 64% yield. This method was also applied to the synthesis of 7-methoxy-3-methylcarbazole-l,4-quinone (113) starting from 3-methoxyaniline (840) (623). Seven years later, Chowdhury et al. reported the isolation of 7-methoxy-3-methylcarbazole-l,4-quinone (113) from the stem bark of Murraya koenigii and named it koeniginequinone A (113) (49) (Scheme 5.101). 

One of the carbazole-l,4-quinones, 3-methoxy-2-methylcarbazole-l,4-quinone (941), required for the total synthesis of carbazomycin G (269), was already used as a key intermediate for the total synthesis of carbazoquinocin C, and was obtained by the addition of aniline (839) to 2-methoxy-3-methyl-l,4-benzoquinone (939), followed by oxidative cyclization with catalytic amounts of palladium(II) acetate (545,645) (see Schemes 5.124 and 5.125). Similarly, in a two-pot operation, 4-meth-oxyaniline (984) was transformed to 3,6-dimethoxy-2-methylcarbazole-l,4-quinone... 

Hibino et al. reported the total synthesis of carbazomycin G (269) by the regioselective addition of methyllithium onto 3-methoxy-2-methylcarbazole-l,4-quinone (941) (653). The required immediate precursor of carbazomycin G, carbazole-l,4-quinone 941, was obtained from 3-(2-methoxyethenyl)-N-(phenylsul-fonyDindole (986). The benzannulation involves an allene-mediated electrocyclic reaction of a 67t-electron system generated from the 2-propargylindole 989, which was derived from the 3-vinylindole 986 in three steps. 

Citral reacted in pyridine with 2-hydroxy-3-methylcarbazole and with 2-hydroxy-7-methoxy-3-methylcarbazole to give ethers 144 (R = H and... 

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