Manganese oxidation cyclization reactions

The reaction of the complex salt 6a with the arylamine 12 affords by regio-selective electrophilic substitution the iron complex 13 [88] (Scheme 11). The oxidative cyclization of complex 13 with very active manganese dioxide provides directly mukonine 14, which by ester cleavage was converted to mukoeic acid 15 [89]. Further applications of the iron-mediated construction of the carbazole framework to the synthesis of 1-oxygenated carbazole alkaloids include murrayanine, koenoline, and murrayafoline A [89]. 

The total synthesis of the carbazomycins emphasizes the utility of the iron-mediated synthesis for the construction of highly substituted carbazole derivatives. The reaction of the complex salts 6a and 6b with the arylamine 20 leads to the iron complexes 21, which prior to oxidative cyclization have to be protected by chemoselective 0-acetylation to 22 (Scheme 13). Oxidation with very active manganese dioxide followed by ester cleavage provides carbazomycin B 23a [93] and carbazomycin C 23b [94]. The regioselectivity of the cyclization of complex 22b to a 6-methoxycarbazole is rationalized by previous results from deuterium labeling studies [87] and the regiodirecting effect of the 2-methoxy substituent of the intermediate tricarbonyliron-coordinated cyclo-hexadienylium ion [79c, 79d]. Starting from the appropriate arylamine, the same sequence of reactions has been applied to the total synthesis of carbazomycin E (carbazomycinal) [95]. 

The carbazole-1,4-quinol alkaloids are also accessible by the iron-mediated arylamine cyclization (Scheme 14). Electrophilic substitution reaction of the arylamine 24 with the complex salts 6a and 6b affords the iron complexes 25. Protection to the acetates 26 and oxidative cyclization with very active manganese dioxide leads to the carbazoles 27, which are oxidized to the carbazole-... 

The total synthesis of carbazomycin D (263) was completed using the quinone imine cyclization route as described for the total synthesis of carbazomycin A (261) (see Scheme 5.86). Electrophilic substitution of the arylamine 780a by reaction with the complex salt 779 provided the iron complex 800. Using different grades of manganese dioxide, the oxidative cyclization of complex 800 was achieved in a two-step sequence to afford the tricarbonyliron complexes 801 (38%) and 802 (4%). By a subsequent proton-catalyzed isomerization, the 8-methoxy isomer 802 could be quantitatively transformed to the 6-methoxy isomer 801 due to the regio-directing effect of the 2-methoxy substituent of the intermediate cyclohexadienyl cation. Demetalation of complex 801 with trimethylamine N-oxide, followed by O-methylation of the intermediate 3-hydroxycarbazole derivative, provided carbazomycin D (263) (five steps and 23% overall yield based on 779) (611) (Scheme 5.91). 

Reaction of the 5-aminochromene 1044 with the complex salt 577 provided via an electrophilic aromatic substitution regio- and diastereoselectively the molybdenum complex 1050. The oxidative cyclization of complex 1050 with concomitant aromatization and demetalation using activated manganese dioxide led directly to girinimbine (115) in 50% yield. Oxidation of girinimbine (115) with DDQ in methanol afforded murrayacine (124) in 64% yield (660) (Scheme 5.161). 

The manganese(UI) acetate mediated oxidative cyclization of fl-ketoesters has been utilized to construct a pentacyclic compound in low yield [95CC403]. The intermediate radical 107 formed from an initial 6-endo-trig reaction undergoes further lactonization in the presence of copper(II) acetate. The compound 108 has the basic skeleton found in fungal metabolite sesquiterpene phenols. 

Electrophilic aromatic substitution of 2,3-dimethyl-4-methoxyani]ine by reaction with the tricarbonyliron-coordinated cyclohexadienylium salt generates the aryl-substituted tricarbonyliron-cyclohexadiene complex. Treatment of this complex with very active manganese dioxide results in oxidative cyclization and aromatization with concomitant demetallation to afford directly 4-deoxycarbazomycin B, a degradation product of the antibiotic carbazomycin B [32]. Using ferricenium hexafluorophos-... 

Oxidations of 2,2 -diaminobiphenyls with sodium perborate, phenyl iodosodiacetate, ° or manganese dioxide have given benzo[c]cinnolines with hydrogen peroxide in acetic acid, cyclization is accompanied by N-oxidation. These reactions, which parallel the oxidation of arylamines... 

Figure 4.11. Examples of redox-initiated radical reactions. Samarium diiodide reduction of the bromide gives a radical that cyclizes faster than the second reduction reaction. Manganese triacetate oxidation of the P-keto ester gives an enol radical that is not further oxidized by the manganese reagent. The IBX oxidizes anilides to the corresponding radicals. Hexamethylphosphoramide = HMPA and Tetrahydrofuran = THE.

Among the oxidants that have been used to generate radicals, manganese (HI) acetate has emerged as a powerful reagent to mediate radical cyclizations.147 The manganese(III) acetate-mediated oxidation of enolizable carbonyl compounds is one of the best methods available for the cyclization of electrophilic radicals. The substrates are vety easily prepared by standard alkylation and acylation reactions. Radicals are formed with high selectivity by oxidation of acidic C—H bonds, and, because the reaction is an oxi-... 

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