Selective substitutions of imidoyl halide in 2-azanorbornenes

Article abstract of DOI:10.1021/jo00377a010

Cyclic imidoyl halides are assumed to undergo nucleophilic substitutions by way of addition-elimination. The imidoyl moiety in azaaldrin (1) has turned out to be a very sensitive substrate in determining the scope and limitation of the addition-elimination pathway of substitution. There was no reaction observed for 1 with 11 common nucleophiles: H, CH₃, CN, SCN, SCH₂Ph, S₂O₃^2-, Br^-, I^-, P(OR)₃, ROH, H₂O. This outcome was not changed by varying solvent or temperature or adding modifiers such as crown ether. However, successful substitutions of 1 and several homologues were obtained with piperidine, fluoride, thiophenolate, ethoxide, and hydroxide in alcohol. The observations are explained by applying Pearson's hard- and soft-base classification of the nucleophiles used. In general, those that are soft bases do not react with 1, while those that are hard and basic do. A mechanism is proposed that involves an early acid-base complex and a transition state stabilized by σ bonding to account for the selectivity of nucleophiles. The structure of the lactam derivative 6 is discussed in detail.