Development of novel carbon-nitrogen bond forming reactions by means of [2,3] sigmatropic rearrangement

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This research has disclosed for the first time that N-alkyl-O-allylic-hydroxylamines (1) rearrange to furnish allylic amines when treated with base such as butyllithium (THF, 0ﾟC, 5min), or thermally without base (DMF, 60ﾟC) depending on the structure of 1. This is unprecedented [2,3]-Wittig type rearrangement in which a migration terminus is a negatively charged nitrogen atom. Taking advantage of hydroxylamine as an N,O-bifunctional nucleophile, we can prepare 1 through a series of routine reactions involving Mitsunobu reaction of allylic alcohols with N-hydroxyphthalimide (Phth-N-OH), generation of O-allylic hydroxylamine with hydrazine, and N-benzylation with benzyl bromide. Hence we have been studying the scope and limitations of this novel [2,3]sigmatropic rearrangement to find that it highly merits organic synthesis as a method for the preparation of stereo-defined allylic amines which are biologically important class of compounds. It also turned out that the reaction was able to be applied to the synthesis of chiral amino polyols relying on substrate-controlled 1,2- and 1,3-asymmetric induction to result in achieving >90%de. Another synthetic potential of this method has been also demonstrated which gives opportunities for the preparation of optically active allylic amines when the reaction is carried out in the presence of chiral diaza-ligand such as bisoxazolines, featuring the first example of reagent-controlled enantioselective [2,3]sigmatropic rearrangement.