A new version of the reverse-Cope elimination initiated by the nucleophilic addition of allylamines to nitrones: a synthesis of vicinal diamines

Abstract

Attempts to utilize the sugar-derived nitrones 1 in enantioselective [1,3]dipolar cycloadditions with protected allylamines 6 are only partly successful, giving mixtures of the expected adducts 7. However, reactions between nitrones 1 and unprotected allylamine 11 follow a different pathway involving sequential nucleophilic addition to the nitrone by the amine, reverse-Cope cyclization and Meisenheimer rearrangement leading to the 1,2,5-oxadiazinanes 12 and 13. Similar reactions with the benzaldehyde derived nitrone 8 are successful, giving the trans-oxadiazinanes 24, 33 and the stereoisomers 38 and 39 from linalylamine 37, but only when the terminus of the allylamine is unsubstituted are the reactions efficient. A range of N-alkylallylamines 43, 45, 47 and 49, however, react smoothly with nitrone 8, as competing imine formation is precluded. Various mechanistic aspects are discussed, along with the effects of aryl substituents in N-benzylallylamines 57 and at the 4-position (59) of the nitrone 8, none of which is found to enhance the overall reaction rate. The initial oxadiazinanes are useful as precursors to both aminohydroxylamines 69 and vicinal diamine derivatives 70.