STERIC EFFECTS VS SECONDARY ORBITAL INTERACTIONS IN NITRONE CYCLOADDITIONS. STERIC EFFECTS IN CYCLOREVERSIONS OF ISOXAZOLIDINES.

Article abstract of DOI:10.1016/S0040-4020(01)86003-8

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 efficiently 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 than (Z)-isomers.These results provide unambiguous experimental evidence that increase in steric compression between the substituents in (Z)-alkenes, on their way toward transition state, is not a major factor in determining their lower reactivity with respect to (E)-isomers in 1,3-dipolar cycloadditions.