Steric Course of Deprotonation/Substitution of Chelating/Dipole‐Stabilizing‐Group‐Substituted α‐Amino‐ and α‐Oxynitriles

The stereochemical course of electrophilic substitutions of -nitrile metallocarbanions was investigated through the deprotonation of enantioenriched -amino- and -oxynitriles bearing a carbamoyl or methoxycarbonyl group in the presence of an electrophile. The results suggested that the dipole-stabilizing substituents not only affected the configurational stability and chemical reactivity of the -nitrile metallocarbanions but could also change the steric course of the electrophilic substitution (retention vs. inversion). Whereas the reaction of an -aminonitrile bearing a dimethylaminocarbonyl group on the nitrogen atom with lithium hexamethyldisilazane in the presence of PhCOCl resulted in the formation of a retention product (93:7), the reaction of an -aminonitrile bearing a methoxycarbonyl group was reversed in favor of the inversion product (37:63). Thus, the methoxycarbonylamino group increased the degree of planarization of the anionic center with maintenance of the planar chirality more than the ureido group, which led to preferential attack of the electrophile from the rear face.