Oxidation, oxazole reactions

Oxazole N-oxides having a 4-methyl substituent are attacked by acetic anhydride to yield 4-acetoxyoxazoles (equation 21). The combined action of benzoyl chloride and potassium cyanide leads to compounds of the Reissert type, e.g. (177). The reaction of 4-methyloxazole Yoxides with phenyl isocyanate gives 5-hydroxy-4-methylene-l-phenyl-4,5-dihy-droimidazoles by cycloaddition, extrusion of carbon dioxide and recyclization (Scheme 12) with 4-phenyloxazole JV-oxides the reaction takes a different course, yielding imi-dazooxazolidinones (Scheme 13). 

Synthesis of 51 commenced with racemic 7-hromotiyptophan methyl ester (52), a three-step process involving treatment with acyl chloride 53, Yonemitsu oxidation and degradation with HBr/AcOH afforded oxazole 54. Condensation of 54 with sulfonamide 55 gave phenol derivative 56, which underwent the key oxidative cycloaddition reaction mediated by PhI(OAc)2 to deliver the desired 57. A three-step functional group manipulation followed by acylation with 7-hydroxy trypt-amine 58 afforded diamide 59. A subsequent two-step benzylic oxidation and cyclodehydration sequence gave bis(oxazoyl)indole 60 (Scheme 8). 

The catalytic oxidative system H/oxidant has also been applied for the synthesis of the following heterocyclic systems 2-imidazolines 134 by the oxidative coupling of benzaldehydes with ethylenediamines [113], benzimidazoles 135 by a similar oxidative coupling reaction of phenylenediamines with aromatic or aliphatic aldehydes [109] and oxazole derivatives 136 by the oxidative coupling of p-ketoesters with benzylamines (Scheme 4.70) [114]. 

Several oxidative catalytic systems utilizing elemental iodine as the catalyst have been developed. Wang and colleagues have reported several tandem oxidative cyclization reactions using I2 as a catalyst and 70% aqueous TBHP (Bu OOH) as a stoichiometric oxidant (Scheme 4.77) [119-122], Heteroaromatic compounds such as oxazoles 151, quinazolines 152 and pyridine derivatives 153 were synthesized in moderate to high yields under these catalytic conditions. The authors suggested that the h/l catalytic cycle might play an important role in the radical mechanism under these conditions [122]. 

Naphth[2,l-d]oxazole, 2-methyl-oxidation, 6, 188 reactions, 6, 216 Naphthoxazoles, anilino-alkylation, 6, 189... 

The reaction of 78 with phosphorus pentasulfide in xylene gives the corresponding 2-oxazolethione, which also forms the iV -methyl product with dimethyl sulfate and 4,5-diphenyl-2-methyhnercapto-oxazole in 98% yield on treatment with silver oxide-methyl iodide. 

The base-catalysed reaction of a-bromo-a,P-unsaturated ketones with aliphatic nitro compounds leads to 2-isoxazoline A-oxides by tandem conjugate addition-ring closure (Scheme 5) <95JOC6624>. A -Acyl-3-isoxazolin-5-ones are transformed into oxazoles by photolysis or by flash vacuum pyrolysis (Scheme 6) <96TL675>. 

Ru, Os, and Ir carbene complexes have been prepared from reactions of anionic or low-valent metal complexes with some organic salts or neutral compounds with highly ionic bonds. Oxidative addition of halothiazole and -oxazole species to IrCl(CO)(PMe2Ph)2 affords Ir(III) complexes which on protonation yield cationic carbenes (69), e.g.,... 

Like thiazole, oxazole is a jt-electron-excessive heterocycle. The electronegativity of the N-atom attracts electrons so that C(2) is partially electropositive and therefore susceptible to nucleophilic attack. However, electrophilic substitution of oxazoles takes place at the electron-rich position C(5) preferentially. More relevant to palladium chemistry, 2-halooxazoles or 2-halobenzoxazoles are prone to oxidative addition to Pd(0). Even 2-chlorooxazole and 2-chlorobenzoxazole are viable substrates for Pd-catalyzed reactions. 

The Michael addition reaction of the serine-derived oxazolidine 326 with ethyl acrylate gave two products. The major product of the reaction was found to be the bicyclic compound 327, which was formed in 27% yield, accompanied by the unsaturated ester 328. The Dess-Martin oxidation of 327 resulted only in formation of the elimination product, the 7,7a-dihydro-177, 377-pyrrolo[l,2-r ]oxazole 328 (Scheme 46) <2001JOC7555>. 

Corey s retrosynthetic concept (Scheme 9) is based on two key transformations a cationic cyclization and an intramolecular Diels-Alder (IMDA) reaction. Thus, cationic cychzation of diene 50 would give a precursor 49 for epf-pseudo-pteroxazole (48), which could be converted into 49 via nitration and oxazole formation. Compound 50 would be obtained by deamination of compound 51 and subsequent Wittig chain elongation. A stereocontroUed IMDA reaction of quinone imide 52 would dehver the decaline core of 51. IMDA precursor 52 should be accessible by amide couphng of diene acid 54 and aminophenol 53 followed by oxidative generation of the quinone imide 52 [28]. 

Two possible mechanisms are proposed. Primarily the enol radical cation is formed. It either undergoes deprotonation because of its intrinsic acidity, producing an a-carbonyl radical, which is oxidized in a further one-electron oxidation step to an a-carbonyl cation. Cyclization leads to an intermediate cyclo-hexadienyl cation. On the other hand, cyclization of the enol radical cation can be faster than deprotonation, producing a distonic radical cation, which, after proton loss and second one-electron oxidation, leads to the same cyclo-hexadienyl cation intermediate as in the first reaction pathway. After a 1,2-methyl shift and further deprotonation, the benzofuran is obtained. Since the oxidation potentials of the enols are about 0.3-0.5 V higher than those of the corresponding a-carbonyl radicals, the author prefers the first reaction pathway via a-carbonyl cations [112]. Under the same reaction conditions, the oxidation of 2-mesityl-2-phenylethenol 74 does not lead to benzofuran but to oxazole 75 in yields of up to 85 %. The oxazole 75 is generated by nucleophilic attack of acetonitrile on the a-carbonyl cation or the proceeding enol radical cation. 

Reaction of Ser-OMe with benzimino ethyl ester resulted in the formation of an oxazoline without racemization (Scheme 27) (85T2379). After forming an amide with 2-amino-l-phenylethanol, Af-phthalimido AAs were oxidized with CrOs and dehydrated by POCI3 to give substituted oxazoles (91JHC1241). 

Dioximes are known to generate isoxazoles and related compounds when oxidized with IBTA. However, these reactions are of limited use because of formation of side products. For example, oxidation of dioximes of /B-diketones 159 gives rise to a mixture of 3,5-disubstituted oxazoles 160 and pyrazole-di-N-oxides 161 (82MI1). In another case, oxidation of dioximes 162 affords a mixture of the isomeric dihydroisoxazolo-isoxazoles 163 and pyridazine dioxides 164 (76S837 79JOC3524 82MI1). 

The hitherto unknown oxazolo[4,5-f]isoxazole system has been synthesized by Nesi et al. in their studies on isoxazoles and their reactions. Oxazole 118 reacts with 1-dimethylaminopropyne through, what the authors describe as a four-step hetero-domino sequence, which they postulate includes a 1,3-dipolar cycloaddition of intermediate nitrile oxide 122 (Scheme 13) <1999T13809>. 

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