Acyclic stereocontrol in [3+2]-cycloadditions of amino acid-derived isomunchnone dipoles

Article abstract of DOI:10.1016/S0040-4020(98)00339-1

α-Diazoimides derived from chiral amines undergo Rh(II)-catalyzed cyclization to give the corresponding chiral isomunchnone dipoles which were trapped with a variety of dipolarophiles. The extent and sense of diastereoselectivity in the [3+2]-cycloaddition is a function of the substitution pattern on the chiral amine. Exo-cycloadducts were formed in high yield, but the π-facial selectivity is low with dipoles derived from 1- phenylethyl amine and 1-(1-naphthalenyl)ethyl amine. However, very high facial discrimination was observed when amino acid esters were used as the chiral amine component. The best results (≤ 95: 5) were obtained using chiral dipoles derived from phenylalanine methyl ester with a variety of dipolarophiles. The observed syn preference can be rationalized in terms of a stereoelectronic effect of the ester functional group in the preferred conformation in the transition state of the cycloaddition. Another possibility involves interaction of the ester carbonyl with the rhodium metal thereby causing the attack of the amido group to occur in a stereodefined manner. Effective shielding of one of the π faces by π-stacking with the aromatic ring explains the high level of π-facial selectivity of the phenylalanine derivatives. The present study introduces a new method for efficient acyclic stereocontrol in isomunchnone cycloaddition reactions.