Nitriles 2.4- disubstituted oxazoles

A new approach to the synthesis of 2,4,5-trisubstituted and 2,5-disubstituted oxazoles, 97 and 98, used l-(methylthio)acetone 95 with nitriles in the presence of trifluoromethanesulfonic anhydride. The proposed mechanism involves an unstable 1-(methylthio)-2-oxopropyl triflate 96 which was detected using NMR spectroscopy <06JOC3026>. 

Several new syntheses of 2,5-disubstituted oxazoles have been reported. The reaction of allyl zinc bromides with )V-cyanomethylimidates (136) leads to 2-alkyl- or aryl-5-allyloxazoles in 50-65% yields after hydrolysis of intermediate imine salts (137) <91SC1501>. The allyl zinc reagents add to the nitrile, in contrast to organolithium and magnesium reagents, which are too basic (Scheme 62). 

The authors initially considered two possible mechanisms. In one case, 384 tautomerized to a nitrile ylide (not shown) that added to 385 and then cycUzed to a 5-(dialkylamino)-4-substituted oxazole. Because none of these products was observed, this mechanism was dismissed. Furthermore, according to this mechanism, reaction of an a-substituted isocyanoacetamide with 385 would give an intermediate incapable of cyclization. This experiment did give a 5-(dialkylamino)-2,4-disubstituted oxazole, which further discounted the viability of such a process. 

Various other [3 + 2] cycloadditions, affording chiral, anellated C6o derivatives with stereogenic centers in the addends are reported in literature. The products were generally obtained as racemates and resulted from reaction of buckminsterfullerene with species like 2,3-disubstituted 2//-azirincs (via nitrile ylides [under direct irradiation] or via 2-azaallenyl radical cations [sensitization by photoinduced electron transfer]),365 1-substituted 5-diazopentane-1,4-diones (via cyclic carbonyl ylides),366 7-alkylidene-2,3-diazabicyclo[2.2.1] hept-2-ene (via a diradicaloid trimethylenemethane derivative),367 1-benzylpy-razolidine-3-ones in the presence of aldehydes (via pyrazolidinium ylides),368 2-trifluoromethyl-2,5-dihydro-l,3-oxazol-5-ones (via nitrile ylides),369 nitro-alkanes in the presence of triethylamine and trimethylsilyl chloride (via N-silyloxynitrones),370 or dv-HOCH2 CH=C H C H 2 OCO 2 H( in the presence of... 

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