Cis and Enantioselective Synthesis of 2-Oxazoline-4-carboxylates through Lewis Acid-Catalyzed Formal [3 + 2] Cycloaddition of 5-Alkoxyoxazoles with Aldehydes

Abstract

In the presence of 2 equiv of ( R )-methylaluminum β-binaphthoxide, which was prepared from ( R )-2,2‘-dihydroxy-1,1‘-binaphthyl and trimethylaluminum, the reaction of 5-methoxy-2-( p -methoxyphenyl)oxazole with benzaldehyde in MeCN gave the corresponding 2-oxazoline-4-carboxylate in high yield (89%) with high stereoselectivity (cis/trans = 92:8) and high enantioselectivity (88% ee (cis)). Under the same conditions, enantioselectivity of the cis products obtained from the reaction with para-substituted benzaldehydes was moderate. On the other hand, formal [3 + 2] cycloaddition of 5-methoxy-2-( o -methoxyphenyl)oxazole with benzaldehyde or para- and meta-substituted benzaldehydes successfully proceeded only in the presence of 30 mol % of ( R )-methylaluminum β-binaphthoxide, which was prepared from ( R )-2,2‘-dihydroxy-1,1‘-binaphthyl and 1.1−1.05 equiv of trimethylaluminum, to give cis -2-oxazoline-4-carboxylates in high enantioselectivity (up to 90% ee).