4.5- disubstituted 2-methyloxazoles

Ogura and co-workers ° reported a general synthesis of 4,5-disubstituted-2-methyloxazoles 190 from attempted amidotellurinylation of internal acetylenes (Scheme 1.50). Normally, terminal acetylenes undergo an F-stereoselective... 

TABLE 1.39. 4,5-DISUBSTITUTED-2-METHYLOXAZOLES FROM O-TRIMETHYLSILYLFORMYLTRIMETHYLSILANE CYANOHYDRIN"... 

Radical bromination with fV-bromosuccinimide often succeeds. Thus, 2,5-disubstituted 4-methyloxazoles on bromina-tion give the 4-bromomethyl compounds, and methyl groups at the 4- or 5-positions of isoxazoles 568 and 569 can be brominated with NBS. Controlled mono- or dibromination of 3-aryl-5-methylisoxazole-4-carboxylates allows access to aldehydes <2004T2301>. 

The ammonium formate in formic acid procedure has rendered possible the first preparation of isomeric 4,5-disubstituted oxazoles.03101 Bredereck, Gompper, and Reich101 have reported the anomalous behavior of certain long-chain a-bromo ketones a single a-bromo ketone on reaction with ammonium formate in formic acid gives a mixture of two isomeric oxazoles. Refluxing of a-bromo ketones or of a-chloro-/3-keto esters with ammonium acetate in acetic acid results in the formation of substituted 2-methyl-oxazoles.40 102 Ethyl a-chloroacetoacetate on heating with ammonium carbonate or formamide in formic acid yields 4-methyloxazole-5-carboxylic ester.40 103... 

Irradiation of a methanolic solution of an oxazole at —78°C in the presence of O2 and rose bengal produced a 2,5-disubstituted 5-hydroperoxy-4-methoxy-4,5-dihydrooxazole 709 (Scheme 1.197). Here again, the oxazole substitution pattern determined the product distribution. For example, 4,5-diphenyl-2-methyloxazole 231a produced only N, iV-dibenzoyl acetamide 706 (Ri = CH3, R2 = R3 = CeHs). On the other hand, 4-methyl-2-phenyloxazole 701a gave 709 (Ri = CgHs, R2 = CH3, R3 = H), which decomposed on warming to room temperature to yield... 

Both 1005 and 1008 (X = H) are readily acylated by an activated ketene, e.g., dichloroketene or f-butylcyanoketene (Scheme 1.271). The authors isolated excellent yields of the a,a-disubstituted 2-acyl-5-phenyloxazoles 1015a/b (X = H). In contrast, the a,a-disubstituted 2-acyl-4-methyloxazoles 1014a/b were isolated in modest to good yield. Nonethless, the yield of 1014a was an improvement over direct acylation of 3 using dichloroketene. ... 

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