Divergent Reactivity of In Situ Generated Metal Azides: Reaction with N,N-Bis(oxy)enamines as a Case Study

Metal azides generated in situ by ion exchange exhibit divergent reactivity in reaction with cyclic N-alkoxy,N-siloxy-enamines. Depending on the nature of metal and the [M]/N₃^- ratio, addition of the azide ion to the C,C-double bond proceeds with regioselective cleavage of either exo- or endo-cyclic N-O bond leading to cyclic or open-chain α-azidooxime derivatives, respectively. Mechanistic studies in combination with solvent state FTIR spectroscopy and DFT calculations revealed that covalently bound metal azides (Co, Cu, Zn) transfer N₃^- anion to the C,C-double bond through a Lewis acid-assisted S_N ' substitution of trialkylsilyloxy-group. More ionic metal azides (N1, Mg, Al, Sc, Ni, Yb) tend to react by initial nucleophilic attack of N₃^- anion on the silicon atom generating conjugated nitrosoalkenes. α-Azidooxime derivatives prepared by using the designed protocols were stereoselectively reduced to valuable 1,2-diaminoalcohols bearing up to four contiguous stereogenic centers. By reducing the α-azidooxime fragment in a stepwise manner site-selective protection and reductive amination of each of the emerging primary amino groups was achieved.