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

Binitrones 1a and 1b reacted with N-methylmaleimide giving bisisoxazolidine s. Diastereospecific reaction of the phenyl substituted dipole 1a gave 3a w hilst the N-methyl dipole 1b furnished diastereomeric adducts 3b, 4 and 7 c lassified as trans,trans, 3b, cis,cis, 4 and cis,trans adducts 7 (major) ac cording to the relative orientation of the 3-H and 4-H protons on each isox azolidine ring. Similar behaviour was observed in reaction of mono dipoles N-benzylideneaniline N-oxide and N-benzylidenemethylamine N-oxide with phen ylenedimaleimide 2. The N-phenyl dipole reacted highly selectively furnishi ng the trans,trans adduct 8a whilst the N-methyl dipole again gave trans,tr ans 8b, cis,cis 10 and cis,trans adducts 9 (major). Some of the N-methyl su bstituted isoxazolidines (3b, 7, 8b, 9b) displayed a number of very broad s ignals in their rt H-1 NMR spectra which sharpened (and duplicated) on cool ing. By analogy to the corresponding H-1 NMR data of the "hemi-adducts" 5 a nd 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 orie ntated. The isoxazolidine ring in these adducts equilibrates between the o- and i-conformations [Fig. 2] and at -40 degreesC each conformer can be cle arly identified in the H-1 NMR spectrum. No line broadening was observed in the H-1 NMR spectra of any of the N-phenyl substituted adducts. The confor mational freedom of the adducts is thus dictated by the size of the N-isoxa zolidine substituent and the relative orientation of the 3-H and 4-H proton s. All new cycloadducts reported, 3-10, are prepared as racemic mixtures an d stereochemical information portrayed in the drawings implies relative and not absolute relations.