Stereospecificity of 1,.3-dipolar cycloadditions of cyclic nitrones to (E) and (Z)-β-nitrostyrenes

Abstract

3,4-Dihydroisoquinoline-N-oxide (1) reacted readily with (E)-ß-nitrostyrene in a regiospecific reaction to give a mixture of 4-nitro-5-phenylisoxazolidines 3a and 4a resulting from endo and exo (with respect to the nitro group) transition states, respectively. This cycloaddition was found reversible under mild conditions. A careful study disclosed ⩾ 99.89% stereoselectivity thus narrowly circumscribing the possibility of stereochemical leakage over the cycloaddition and cycloreversion processes. Moreover, our experimental data showed that eventual loss of stereochemistry should be ascribed to base catalyzed isomerizations in the adducts and/or in the educts. The reaction of 1 with (Z)-ß-nitrostyrene ( exo specific and regiospecific) turned out to be faster than that of the (E)-isomer. This is the first example of higher reactivity of a cis than a trans-alkene in 1,3-dipolar cycloadditions. The endo-trans adduct 3a cycloreverted faster than the exo-trans isomer 4a which in turn underwent fragmentation more readily than the exo-cis 6a. The cycloreversion rate was slightly enhanced by increased solvent polarity. This study was extended to the reaction of 5,5-dimethylpyrroline-N-oxide with both the cited dipolarophiles.