Simultaneous double 1,3-dipolar cycloaddition reactions involving bisnitrones or bisdipolarophiles. 1H NMR investigation of the conformational preferences of N-methyl- and N-phenyl-isoxazolidines

Abstract

Bisnitrones 1a and 1b reacted with N-methylmaleimide giving bisisoxazolidines. Diastereospecific reaction of the phenyl substituted dipole 1a gave 3a whilst the N-methyl dipole 1b furnished diastereomeric adducts 3b, 4 and 7 classified as trans,trans, 3b, cis,cis, 4 and cis,trans adducts 7 (major) according to the relative orientation of the 3-H and 4-H protons on each isoxazolidine ring. Similar behaviour was observed in reaction of mono dipoles N-benzylideneaniline N-oxide and N-benzylidenemethylamine N-oxide with phenylenedimaleimide 2. The N-phenyl dipole reacted highly selectively furnishing the trans,trans adduct 8a whilst the N-methyl dipole again gave trans,trans8b, cis,cis10 and cis,trans adducts 9 (major). Some of the N-methyl substituted isoxazolidines (3b, 7, 8b, 9b) displayed a number of very broad signals in their rt ¹H NMR spectra which sharpened (and duplicated) on cooling. By analogy to the corresponding ¹H NMR data of the “hemi-adducts” 5 and 6, and with reference to crystal structure data for 5c [Fig. 1], it was shown that for this group of adducts the 3-H and 4-H protons are trans orientated. The isoxazolidine ring in these adducts equilibrates between the o- and i-conformations [Fig. 2] and at −40 °C each conformer can be clearly identified in the ¹H NMR spectrum. No line broadening was observed in the ¹H NMR spectra of any of the N-phenyl substituted adducts. The conformational freedom of the adducts is thus dictated by the size of the N-isoxazolidine substituent and the relative orientation of the 3-H and 4-H protons. All new cycloadducts reported, 3–10, are prepared as racemic mixtures and stereochemical information portrayed in the drawings implies relative and not absolute relations.