Steric effects vs secondary orbital interactions in nitrone cycloadditions : Steric effects in cycloreversions of isoxazolidines

3,4-Dihydroisoquinoline-N-oxide 1 reacted readily with both acyclic (Z)- and (E)-disubstituted alkenes bearing electron-attracting substituents (methoxycarbonyl, cyano, phenylsulphonyl and benzoyl groups) and with cyclic derivatives (e.g. maleimides) to give mixtures of the two possible diastereoisomers. Similar amounts of endo - and exo -adducts were formed in the reactions of (Z)-cyano, methoxycarbonyl and benzoyl derivatives whereas exo -addition clearly won over its endo -counterpart in the case of (Z)-(phenylsulphonyl) and cyclic derivatives. High exo -selectivity was also observed in the sluggish reactions of 1 with electron-rich alkenes [(Z)-stilbene, vinylene carbonate, acenaphthylene etc.] Our results, which revise previous literature data, clearly show that an “ endo -rule” does not hold for the reactions of 1 with (Z)-1,2-disubstituted alkenes. We conclude that in these reactions repulsive steric interactions either counteract efficientlt or clearly win over stabilizing secondary orbital overlaps in controlling endo/exo -selectivity. These reactions were found reversible under mild conditions so that relative formation rates of related pairs of (Z)- and (E)-dipolarophiles in cycloreversion processes of isoxazolidines could be determined; as a rule (E)-alkenes are extruded faster then (Z)-isomers. These results provide unambiguous experimehntal evidence that increase in steric compression between the substituents in (Z)-alkenes on there way toward transition state, is not a major factor in dertermining their lower reactivity with respect to (E)-isomers in 1,3-dipolar cycloadditions.