Stereoselective synthesis of 2-oxazoline-4-carboxylates through lewis acid-catalyzed formal [3 + 2] cycloadditions of 5-alkoxyoxazoles with aldehydes: Catalytic effect of methylaluminum β-binaphthoxide on cis- selectivity

Article abstract of DOI:10.1021/jo00078a018

The formal [3 + 2] cycloadditions of 5-methoxy-2-(p-methoxyphenyl) oxazole with benzaldehyde, para- and meta-substituted benzaldehydes, propanal, cinnamaldehyde, and heterocyclic carboxaldehydes in the presence of methylaluminum β-binaphthoxide gave the corresponding methyl 5-alkyl-2-(p- methoxyphenyl)-2-oxazoline-4-carboxylates with high cis-selectivity (up to 98%). The use of ortho-substituted benzaldehydes resulted in a decrease in the cis-selectivity. The reaction of 5-methoxy-2-(p-methoxyphenyl)oxazole with benzaldehyde in the presence of titanium(IV) chloride or tin(IV) chloride gave the corresponding trans-2-oxazoline-4-carboxylate with 85-86% trans-selectivity. The reaction of ethyl glyoxylate with 5-ethoxy-2- phenyloxazole catalyzed by a 1:1 mixture of titanium(IV) chloride and titanium tetraisopropoxide gave diethyl 2-phenyl-2-oxazoline-4,5- dicarboxylate with a preference for cis-selectivity (cis/trans = 84:6). The cis-selectivity of the reaction in the presence of methylaluminum β- binaphthoxide can be explained by an antiperiplanar approach of the C4-C5 double bond of the oxazole to the aldehyde coordinated to the catalyst, followed by ring opening of the oxazole through a stepwise pathway involving zwitterionic intermediates.