SUBSTITUTED OXAZOLES - SYNTHESES VIA LITHIO INTERMEDIATES

Reactions of 2-alpha-, 2-, 4-, and 5-lithiooxazoles are used to prepare various substituted derivatives. Previously unrecognized time dependence for the reaction of a 2-lithiooxazole with benzaldehyde is described, and a rationale for this behavior is offered. Competitive reactions occur when the readily available 2,5-diphenyloxazole is treated with n-butyllithium. Deprotonation of the ortho position of the 2-phenyl group and addition of n-butyl to the 2-position of the oxazole compete with the desired 4-lithiation. The use of sec-butyllithium/catalytic lithium tetramethylpiperidide allows preferential formation of 4-lithio-25-diphenyloxazole. This intermediate has been converted to the 4-bromo, -methyl, -hydroxybenzyl, -benzoyl, and -trialkylsilyl derivatives. Lithiation of 2,4-diphenyloxazole and subsequent trimethylsilylation occur readily at the 5-position. Deprotonation of 2-alkyloxazoles occurs at the alpha-carbon in preference to ring sites. Further reaction of an alpha-phenyl-2-oxazolemethanol methoxymethyl ether with base and acetyl chloride leads to an acyloin derivative. Chromic acid oxidation is used to prepare both 2- and 4-benzoyloxazoles. The formation of a 2-ethoxyoxazole from the 2-oxazolone vis Meerwein salt chemistry is described.