3.5- Disubstituted oxazoles, from oxidation

Oxazole IV-oxides cannot be made by oxygenation of oxazoles. The only method of synthesis remains the condensation of monooximes of 1,2-dicarbonyl compounds with aldehydes in the presence of hydrogen chloride (equation 132) (15CB897). The aldehyde may be aromatic or aliphatic (including formaldehyde) and the oxime may be derived from an aromatic diketone or it may be an a-keto aldoxime, leading to a 2,5-disubstituted oxazole IV-oxide. It may also contain an additional carbonyl group as in equation (133). 

The synthesis of 2,5-disubstituted oxazoles from methyl ketones and benzylamines in a metal and peroxide-free environment is achieved using l2-promoted domino oxidative cyclization involving C-H bond cleavage and the formation of C-N and C-0 bonds. Slow oxidation of A-acetyl homocysteine thiolactone by iodate to A-acetyl homocysteine thiolacone sulfoxide occurs in a reaction S1 having 1 3 stoichiometry (oxidant reductant). The stoichiometric ratio in excess of 103 (reaction S2) is 2 5 because excess 103 oxidizes the r ion, generated in reaction SI, to I2. The stoichiometry ratio for the I2 oxidation (reaction S3) is 1 1. Complex kinetics are observed because reactions SI, S2 and S3 occur simultaneously with comparable rates. 

TABLE 1.36. 2,5-DISUBSTITUTED 4-OXAZOLECARBOXYLIC ACID ESTERS, 2,4,5-TRISUBSTITUTED OXAZOLES, AND 2,4 -BIS-OXAZOLES FROM DESS-MARTIN PERIODINANE OXIDATION AND (CeHslsP/yiCzHjlsN CYCLIZATION-... 

Utilizing mild 1(111) reagent, Phl(OTf)2 and readily available N-styrylamides 46, Hempel, and Nachtsheim prepared various 2,5-disubstituted oxazoles 47 in high yields. This intramolecular oxidative cyclization of N-styrylamides to oxazoles was promoted via generation of Phf(OTf)2 from the combination of PIFA with trimethylsilyltrifluorometh-anesulfonate (TMSOTf) (Scheme 6) [22],... 

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