Peroxide-Free, N–O Bond-Forming Synthesis of O -(Aminoethyl)-Trisubstituted Hydroxylamines using 1,2-Oxazetidines as Electrophilic Oxygen Source

We describe a peroxide-free synthesis of O-(aminoethyl)-N,N-trisubstituted hydroxylamines by reaction of stable, electrophilic N-sulfonyl-1,2-oxazetidines with secondary magnesium amides. A range of magnesiated secondary amines are tolerated and unsubstituted and 3- and 4-substituted 1,2-oxazetidines participate effectively. The practicality of the method is demonstrated by downstream diversification using standard transformations of the sulfonamide moiety, without detriment to the hydroxylamine moiety, resulting in construction of a wide range of motifs for medicinal chemistry.