Esters manganese dioxide

Several total syntheses of antirhine (11) and 18,19-dihydroantirhine (14) have been developed during the last decade. Wenkert et al. (136) employed a facile route to ( )-18,19-dihydroantirhine, using lactone 196 as a key building block. Base-catalyzed condensation of methyl 4-methylnicotinate (193) with methyl oxalate, followed by hydrolysis, oxidative decarboxylation with alkaline hydrogen peroxide, and final esterification, resulted in methyl 4-(methoxycar-bonylmethyl)nicotinate (194). Condensation of 194 with acetaldehyde and subsequent reduction afforded nicotinic ester derivative 195, which was reduced with lithium aluminum hydride, and the diol product obtained was oxidized with manganese dioxide to yield the desired lactone 196. Alkylation of 196 with tryptophyl bromide (197) resulted in a pyridinium salt whose catalytic reduction... 

Aldehyde 244 reacts with manganese dioxide and sodium cyanide in ethanol to give ethyl ester 245 (Scheme 19), while oxidation of alcohol 12 with sodium peroxodisulfate in the presence of a catalytic amount of ruthenium chloride furnishes the carboxylic acid 246 (Scheme 19) <1998CPB287>. 

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]. 

An alternative access to murrayanine (9) was developed starting from the mukonine precursor 609. The reduction of the ester group of 609 using diisobutylaluminum hydride (DIBAL) afforded the benzylic alcohol 611. In a one-pot reaction, using very active manganese dioxide, 611 was transformed to murrayanine (9) (574) (Scheme 5.36). 

Oxidation of 48 using manganese dioxide in methanol in the presence of potassium cyanide provides clausine H (clauszoline-C) (50) quantitatively, which on ester cleavage affords clausine K (clauszoline-J) (51). Cleavage of both methyl ethers of 51 on treatment with boron tribromide led to clausine O (72) (588). 

The total synthesis of carbazomycin C (262) was achieved by executing similar reaction sequences as in the iron-mediated arylamine cyclization route described for the synthesis of carbazomycin B (261) (see Scheme 5.87). The electrophilic substitution of the arylamine 780b using the complex salt 779 afforded the iron complex 797, which was transformed to the corresponding acetate 798. Using very active manganese dioxide, compound 798 was cyclized to O-acetylcarbazomycin C (799). Finally, saponification of the ester afforded carbazomycin C (262) (four steps and 25% overall yield based on 779) (611) (Scheme 5.90). 

Clauszoline-K (98) was transformed quantitatively to clausine C (clauszoline-L) (101) by treatment with manganese dioxide and potassium cyanide in methanol. Ether cleavage of clausine C (101) gave clausine M (102), while saponification of the ester led to clausine N (103) (Scheme 5.150). 

Synthesis of the pyrazino[2,1 -bjquinazoline (557) was achieved by oxidative cyclization of the l-(2-aminobenzyl)-4-methylpiperazine (556) with manganese dioxide [68JCS(C)1722], the pyrimidine ring of 557 was formed during this synthesis. The pyrimidine ring of 559 was also formed upon cyclocondensation of anthranilic acids with the cyclic imidate ester (558), followed by removal of the protective group (66USP3280117). 

Oxidative cyclization of the 4-(2-aminobenzyl)-l,4-oxazine (576) with manganese dioxide gave the 1,4-oxazino[3,4-6]quinazoline (577) through the formation of its pyrimidine ring [68JCS(C)1722]. Cyclocondensation of anthranilic acids with the thioimidate ester (578) gave 3,4-dihydro-l,4-oxazino[3,4-6]quinazolin-6(l/f)-ones (579) [791JC(B) 107]. 

The structure of the methyl ester m.p. 174° C. (XL) was proven (5) mainly by the fact that the corresponding dibasic acid (XLI R = H) and its dimethyl ester (XLI R = Me) are oxidized with periodate and that the dimethyl ester is oxidized by manganese dioxide to a trisubstituted a,/ -unsaturated ketone (XLII) which regenerates (XLII R = Me) with sodium borohydride. 

Oxidation of hemiacetals.1 Pyridinium dichromate in DMF effects a novel oxidative cyclization of the aldehyde 1 to the macrocyclic lactone verrucarin T (2a). The conversion is believed to involve cyclization to a hemiacetal (2b) followed by oxidation to 2a. Manganese dioxide does not oxidize 1, and a variety of other oxidants attack the dienic ester side chain. 

Figure 19.1 Synthetic scheme for example pheromone components. Abbreviations al and a2 = Wittig-Homer condensations with triethyl 2-phosphonopropionate and triethyl 2-phosphonobutyrate, respectively b = reduction of ester with lithium aluminum hydride c = partial oxidation of alcohol with manganese dioxide to aldehyde dl and d2 = Wittig condensations with ethyltriphenylphosphonium bromide and propyltriphenylphosphonium bromide, respectively e = condensation with dimethylhydrazone phosphonate reagent f = hydrolysis under acidic conditions. Compound numbers are as in Table 19.1.

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