Oxidation, oxazole reactions 4 + 2 cycloaddition

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). 

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>. 

The attacks of heterocyclic A -oxides, e.g. of pyridine, quinoline, isoquinoline, phenanthridine, etc., on activated alkynes (RC CR R = R = COOMe R = Ph, R = COOEt R = Ph, R = CN) pose similar problems . An acyclic intermediate has been postulated but is rarely detected. Some of the possibilities are illustrated in equation (126) . If the open intermediate is formed, then the paths to the ylid and the 2-substituted quinoline in equation (126) seem simple enough, but several possible mechanisms can lead to the 3-substituted products . Other workers regard the reaction of the nitrone (or azomethine oxide) with alkyne as simple cycloadditions - which yield 2,3-dihydro-l,2-oxazoles since these are often unstable, only decomposition products may be found (equation 127). The construction of the indolizine skeleton initiated by a similar process has been reviewed (equation 128). ... 

There are general reviews on heterocyclic syntheses by cycloaddition reactions of isocyanates and on the use of heterocyclic cations in preparative organic chemistry. More specific topics are 5-hydroxymethylfuran-2-carb-aldehyde, isobenzofurans and related ort/io-quinonoid systems, the conversion of 2//-cyclohepta[Zj] furan-2-one (1) into derivatives of azulene, the synthesis of indoles from o-alkylphenyl isocyanides, and abnormal Fischer indolization reactions of o-methoxyphenylhydrazones. Two reviews on isoindoles have appeared and a lecture on highly conducting charge-transfer complexes that are based on heterocyclic selenium and tellurium donors has been reprinted.Recent advances in the chemistry of imidazole and in the use of nitro-imidazoles as radiosensitizers have been summarized. There have been reviews on benzimidazole A -oxides and on dihydrobenzimidazoles, benzimidazolones, benzimidazolethiones, and related compounds. Other topics are synthetic applications of 1,3-dithiolium and 1,3-oxathiolium salts and of isoxazoles, the chemistry of benzisoxazoles, 2-amino-oxazoles, 5-oxazolones (2), furoxans, benzofuroxans, and related systems, the synthesis of five-membered meso-ionic compounds, and tetrazoles. ... 

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 fused oxazole derivative 100 was synthesized from 3-azido-3-deoxy-l,2 5,6-di-O-isopropylidene-a-D-allofuranose, the key final step being the reaction of methyl 3-amino-3-deoxy-5,6-0-isopropylidene-p-D-alloside with DMF dimethyl acetal. The annelated pyranoside 101 was obtained by cyclization of a branched chain hexosulose derivative, and the fused triazole-piperidinoses such as 102 were made by a radical cyclization of a 3-pyrazolo-6-iodo-sugar derivative. The spiro-isoxazohne 103 and related isomers have been synthesized by dipolar cycloadditions of mesitonitrile oxide to 2-deoxy-2-C-methyl-ene-pentonic acids, themselves available in five steps from D-mannitol. Intra-... 

It is worth noting that one C-N, one C-O, and three C-C bonds were formed with the concomitant creation of five asymmetric centers in this one-pot process. The oxazole 65 could be isolated if the reaction was performed at rt Significantly, the same reaction using ortHo-aminophenyl propiolate 67 instead of 64 in the presence of ammonium chloride furnished furoquinoline 69 in 75% yield (Eq. (2), Scheme 15.22) [39]. The intramolecular DA cycloaddition of 68 followed by retro DA and oxidation accounted for the formation of 69. These two examples demonstrated how subtle structural modification of one input (64 vs 67) in a given MCR could diversify the structure of the reaction product Compound 66 is a product with up to five stereocenters, while 69 is a flat aromatic heterocycle. 

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