Lewis acid catalyzed formal [3+2] cycloaddition of 5-alkoxyoxazoles and thiiazoles

In contrast to the regioselectivity under thermal conditions in the reactio n of 5-alkoxyoxazoles with diethyl oxomalonate, the 5-alkoxy-2-aryloxazoles undergo formal [3 + 2] cycloaddition in the presence of tin(IV) chloride t o give 5,5-di(ethoxycarbonyl)-2-oxazoline-4-carboxylate with high regiosele ctivity. Lewis acid catalyzed reactions of 5-alkoxyoxazoles with aldehydes also gave 2-oxazoline-4-carbaxylates regioselectively. The use of titanium( IV) chloride and tin(IV) chloride for the reaction with aldehydes afforded trans-2-oxazoline-4-carboxylate predominantly. In the presence of 2 equivs. of methyl aluminum beta-binaphthoxide, the reaction of 2-(p-methoxyphenyl) -5-methoxyoxazole with various aldehydes gave cis-2-oxazoline-4-carboxylate s with high stereoselectivity (up to 98% selectivity). The reaction with be nzaldehyde, para- and meta-substituted benzaldehydes in the presence of 30 mol% of the chiral catalyst gave cis-2-oxazoline-4-carboxylates with high e nantioselectivity (up to 90% eel. The formal [3 + 2] cycloaddition reaction with chiral alpha-alkoxyaldehydes in the presence of tin(IV) chloride also proceeds with high diastereoselectivity. On the other hand, the reaction o f diethyl oxomalonate in the presence of tin(IV) chloride with 4-unsubstitu ted 5-alkoxythiazoles does not give similar adducts but affords diethyl 2-h ydroxy-2-(4-thiazolyl)malonates through an electrophilic substitution react ion of thiazole at C-4.