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 SN′ 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.