Lewis Acid Promoted Reactions of Diazocarbonyl Compounds. 3. Synthesis of Oxazoles from Nitriles through Intermediate β-Imidatoalkenediazonium Salts

Article abstract of DOI:10.1021/jo01306a023

Lewis acid promoted reactions of α-diazocarbonyl compounds with nitriles provide a general method for the production of oxazoles in high isolated yields.The generality of this method is evaluated by the effectiveness of oxazole formation in surveys of Lewis acids, diazocarbonyl compounds, and nitriles.Because of the relative absence of α-halogenation products in reactions performed with BF3*Et2O, this Lewis acid is preferred when the nitrile is employed as the reaction solvent.Reactions of diazo ketones in nitrile solvents generally result in higher oxazole yields(70-99percent) than do reactions of ethyl diazoacetate (26-31percent).When these transformations are performed at or below room temperature, at least 1 equiv of the Lewis acid is required, although catalytic activity is observed in reactions performed at 65 deg C.In BF3*Et2O promoted reactions, a minimum tenfold molar excess of nitrile is required for optimum oxazole production, although use of SbF5 results in high yields of oxazoles even when only a threefold excess of the nitrile is employed.The mechanism for oxazole formation is established as involving initial activation of the nitrile through association with the Lewis acid, followed by attack of the nitrilium complex at the carbonyl oxygen of the diazocarbonyl compound and internal displacement of nitrogen.Although Lewis acid association with the diazocarbonyl compound is the more favorable process in reactions performed with equivalent amounts of nitrile and diazocarbonyl compound, only equilibrium association of the Lewis acid with the nitrile effectively leads to oxazole formation.