Nitriles 2-alkyl-5-aryloxazoles

Gogonas and Hadjiarapgolu described the synthesis of oxazoles via a Rh2(OAc)4-catalyzed [3 + 2]-cycloaddition reaction of phenyliodonium salts with nitriles (Scheme 1.46). The starting phenyliodonium salt 167 was prepared from dimedone and diacetoxyiodobenzene in 95% yield. Reaction of 167 with nitriles in the presence of Rh2(OAc)4 gave fused 2-alkyl-, 2-aralkyl-, or 2-aryloxazoles 168 in modest yields. It is noteworthy that the reaction conditions do not require an inert atmosphere. The mechanistic details of this reaction are not yet clear. Selected examples are shown in Table 1.10. 

Lee and Hong" described the first direct synthesis of 2-alkyl-5-aryloxazoles 206 from aromatic a-methyl ketones (Scheme 1.57). They used thallium(III)triflate generated in sim to convert a ketone to the a-ketotriflate 204. Reaction of 204 with a nitrile most likely produces a nitrilium salt 205, as proposed by Meyers and Sicar, which subsequently cyclizes to 206. The reaction works well for aliphatic nitriles regardless of steric hindrance. Aromatic nitriles are not as useful,... 

In a complementary approach for preparing a-ketotriflates Varma and Kumar used the combination of iodobenzene diacetate and trifluoromethanesulfonic acid to prepare p-oxobis[trifluoromethanesulfonato(phenyl)iodme] 207 in situ. This reagent cleanly converted aromatic a-methyl ketones to the corresponding a-ketotriflates 204, which reacted with nitriles to afford 2-alkyl-5-aryloxazoles 206 in variable yield (Scheme 1.58). Mechanistically, the authors proposed the same... 

TABLE 1.15. 2-ALKYL-5-ARYLOXAZOLES FROM AROMATIC a-METHYL KETONES, NITRILES, AND THALLIUM TRIFLATE"... 

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See also in sourсe #XX -- [ , , , ]

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