Imidazole catalyst, oxidation with

In the studies of the synthesis of the ansamycin antibiotic rifamycin S (13S), Corey and Clark [76] found numerous attempts to effect the lactam closure of the linear precursor 132 to 134 uniformly unsuccessful under a variety of experimental conditions, e.g. via activated ester with imidazole and mixed benzoic anhydride. The crux of the problem was associated with the quinone system which so deactivates the amino group to prevent its attachment to mildly activated carboxylic derivatives. Cyclization was achieved after conversion of the quinone system to the hydroquinone system. Thus, as shown in Scheme 45, treatment of 132 with 10 equiv of isobutyl chloroformate and 1 eqtuv of triethylamine at 23 °C produced the corresponding mixed carbonic anhydride in 95% yield. The quinone C=C bond was reduced by hydrogenation with Lindlar catalyst at low temperature. A cold solution of the hydroquinone was added over 2 h to THF at 50 °C and stirred for an additional 12 h at the same temperature. Oxidation with aqueous potassium ferricyanide afforded the cyclic product 134 in 80% yield. Kishi and coworkers [73] gained a similar result by using mixed ethyl carbonic anhydride. 

Different metal oxides (silica, alumina, and titania) are utilized as solid catalysts in the high-temperature ( 400°C) acylation of 2-methyl-imidazole 38 with AAN under a nitrogen stream (Scheme 4.27).i 4-Acetyl-2-methylimidazole 39 is produced in 65% yield in the presence of silica. The method is applied to the large-scale preparation of acylated imidazoles variously substituted on the heteroaromatic ring. 

In an analogous approach, the effect of imidazole was also observed by Inoue et al. [114]. When alkyl aryl sulfides were oxidized with a novel iron porphyrin catalyst (52) (0.2 mol% equiv), the reaction proceeded enantioselectively under appropriate conditions. Iodosobenzene was used as oxidant in dichloromethane at -43°C. The turnover number increases to 142, and an ee of 73% was obtained in the presence of a 100 to 600 molar ratio of imidazole to catalyst for the synthesis of (5)-methoxymethyl phenyl sulfoxide. In the absence of imidazole, the enantioselectivity disappeared, giving the racemic sulfoxide. 

The epoxidation of olefins in the presence of ethyl 2-oxocyclopentanecarboxylate as co-substrate by 1/f-imidazole and air using FeCl3 6H20 in MeCN as catalyst was achieved with fair to excellent chemoselectivities. The epoxidation was caused by an active iron species generated by O2, which was activated by the co-substrate. The process involved 4e , instead of 2e , reduction of the O2 molecule in the commonly used peroxides. Aromatic olefins were also oxidized in high yields with excellent chemoselectivity.i2 ... 

With the first nucleoside in place, we are ready to attach to it the second. For this purpose, the point of attachment, the 5 -OH, is deprotected with acid. Subsequent addition of a 3 -OH activated nucleoside effects coupling. The activating group is an unusual phosphoramidite [containing P(III)], which, as we shall see shortly, also serves as a masked phosphate [P(V)] for the final dinucleotide and is subject to nucleophilic substitution, not unlike PBrs (recall Sections 9-4 and 19-8). The displacement reaction is catalyzed and furnishes a phosphite derivative the catalyst is the, again unusual, aromatic heterocycle tetrazole, a tetrazacyclopentadiene related to pyrrole (Section 25-3) and imidazole (Section 26-1). Finally, the phosphorus is oxidized with iodine to the phosphate oxidation state. 

The introduction of chlorinated porphyrins (10) allowed for hydrogen peroxide to be used as terminal oxidant [62], These catalysts, discovered by Mansuy and coworkers, were demonstrated to resist decomposition, and efficient epoxidations of olefins were achieved when they were used together with imidazole or imidazo-lium carboxylates as additives, (Table 6.6, Entries 1 and 2). 

The observation that addition of imidazoles and carboxylic acids significantly improved the epoxidation reaction resulted in the development of Mn-porphyrin complexes containing these groups covalently linked to the porphyrin platform as attached pendant arms (11) [63]. When these catalysts were employed in the epoxidation of simple olefins with hydrogen peroxide, enhanced oxidation rates were obtained in combination with perfect product selectivity (Table 6.6, Entry 3). In contrast with epoxidations catalyzed by other metals, the Mn-porphyrin system yields products with scrambled stereochemistry the epoxidation of cis-stilbene with Mn(TPP)Cl (TPP = tetraphenylporphyrin) and iodosylbenzene, for example, generated cis- and trans-stilbene oxide in a ratio of 35 65. The low stereospecificity was improved by use of heterocyclic additives such as pyridines or imidazoles. The epoxidation system, with hydrogen peroxide as terminal oxidant, was reported to be stereospecific for ris-olefins, whereas trans-olefins are poor substrates with these catalysts. 

When dopa was oxidized using the PIPo-Cu catalyst, the distinguished acceleration was observed as compared with the PVIm-Cu or imidazole-Cu catalysts (Fig. 6). An increase in content of the N-vinylpyrrolidone residue in the PIPo copolymer caused higher activity of the Cu complex for the dopa oxidation. The similar acceleration was also produced when N-methyl-pyrrolidone was added to the system of PVIm-Cu. However, nearly 103 fold concentration of the pyrrolidone residue was necessary as compared with the PIPo copolymer. Addition of homopolymer of N-vinyl-pyrrolidone to PVIm-Cu caused no acceleration. 

Without additives, radical formation is the main reaction in the manganese-catalyzed oxidation of alkenes and epoxide yields are poor. The heterolytic peroxide-bond-cleavage and therefore epoxide formation can be favored by using nitrogen heterocycles as cocatalysts (imidazoles, pyridines , tertiary amine Af-oxides ) acting as bases or as axial ligands on the metal catalyst. With the Mn-salen complex Mn-[AI,AI -ethylenebis(5,5 -dinitrosalicylideneaminato)], and in the presence of imidazole as cocatalyst and TBHP as oxidant, various alkenes could be epoxidized with yields between 6% and 90% (in some cases ionol was employed as additive), whereby the yields based on the amount of TBHP consumed were low (10-15%). Sterically hindered additives like 2,6-di-f-butylpyridine did not promote the epoxidation. 

Like many of the nitrogen heterocycles possessing tetrahydroxybutyl side-chains (which tend to form anhydrides), the unsubstituted imidazoline-2-thione 92 readily loses water on heating its aqueous solution under pressufe,97 to give 93, and as with other 1-substituted 2-thiones, it is converted into the 1-aryl-4-(D-arabino-tetrahydroxyl-butyl)imidazole (94) by desulfurization followed by oxidation of the product with oxygen in the presence of a platinum catalyst.98... 

Imidazolones, particularly 2-imidazolones, give the corresponding chloro derivatives when heated with phosphoryl chloride, especially with copper(I) chloride as catalyst [76MI1 80AJC1545 90EGP3828208]. The same reagents convert imidazole N-oxides into 2-chloroimidazoles [75JCS(P1)275]. 

---