Oxidative cleavage manganese dioxide

The heterocycle 3-methyl-1,2-benzisoxazole, whilst structurally distinct from the phenolic aryl ethers underwent cleavage at the 0-N bond by slow addition in tetrahydrofuran to 1M lithium diethylamide at -75 C followed by isolation of crude 1,6-dihydropyridazine and its oxidation with manganese dioxide over 1 hour to give 3,5-bis(2-hydroxyphenyl)pyridazine in 61% yield (ref.96). 

Nickel peroxide is a solid, insoluble oxidant prepared by reaction of nickel (II) salts with hypochlorite or ozone in aqueous alkaline solution. This reagent when used in nonpolar medium is similar to, but more reactive than, activated manganese dioxide in selectively oxidizing allylic or acetylenic alcohols. It also reacts rapidly with amines, phenols, hydrazones and sulfides so that selective oxidation of allylic alcohols in the presence of these functionalities may not be possible. In basic media the oxidizing power of nickel peroxide is increased and saturated primary alcohols can be oxidized directly to carboxylic acids. In the presence of ammonia at —20°, primary allylic alcohols give amides while at elevated temperatures nitriles are formed. At elevated temperatures efficient cleavage of a-glycols, a-ketols... 

The oxidation of 104 occurs readily with 1 equiv of manganese dioxide in 4 h to give seco-pz (162) (77%). Prolonged reaction times, or the use of an excess of the oxidant, results in reduced yields of 162, along with some second pyrrole cleavage and decomposition. If pz 104 is treated with 2 equiv of manganese dioxide for 24 h, the rather unstable product of overoxidation, diseco-porphyrazine 163 can isolated in up to 41% yield (Scheme 30) (8). 

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]. 

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). 

Oxidation of 3-formyl-6-methoxycarbazole (97) with manganese dioxide and potassium cyanide in methanol afforded methyl 6-methoxycarbazole-3-carboxylate (104). Regioselective bromination of 97 afforded the 5-bromocarbazole 1031. Cleavage of the methyl ether to 1032, followed by nickel-mediated prenylation, provided micromeline (100) (547) (Scheme 5.154). 

The methylene bridge in the fused oxazoline (203), 6-methyl-2//,6//-oxazolo[5,4,3-j/]quinolin-4-one, shows great stability towards acid cleavage, such as heating in 47% hydriodic acid. It is cleaved by oxidation, however, when treated with activated manganese dioxide in acetic acid (73JA5003). 

Two oxidants essentially dominate these oxidations lead tetraacetate in organic solvents and periodic acid in aqueous media. On occasion, other oxidation reagents cause the cleavage of vicinal diols ceric ammonium nitrate [424], sodium bismuthate [482, 483], chromium trioxide [482, 555], potassium dichromate with perchloric acid [949], manganese dioxide [817], and trivalent [779, 789] or pentavalent [798] iodine compounds. 

Solaverbascine, occurring in S. verbasoifolium leaves, has been assigned structure (57) from spectral study and because it is formed by reductive ring-cleavage of solaso-dine (44) (G. Adam et al., Phytochem., 1980, 1, 1002) conversely it affords solasodine on manganese dioxide oxidation (Adam and H. T. Huong, Tetrahedron Letters, 1980, 21, 1931 J. prakt. Chem., 1981, 323, 839). The latter reaction occurs via 22-n double bond formation followed by spontaneous cyclization. 

The reactivity of four oxidizing reagents, sodium bismuthate, sodium periodate, manganese dioxide and lead tetraacetate, has been compared in the oxidative cleavage of unsaturated alicyclic a-ketols to a)-oxo-a,j8-unsatu-rated acids [93JOC2196]. Sodium bismuthate cleaved saturated a-ketols but not unsaturated ones (Scheme 5.3). 

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