Stereochemical Course of Deprotonation-Acylation of <i>N</i>‑Boc- and <i>N</i>‑Carbamoyl-2-cyano-6-methylpiperidines

The stereochemical course of electrophilic substitution of α-nitrile metallocarbanions generated by deprotonation from N-Boc- and N-carbamoyl-2-cyano-6-methylpiperidines was investigated. Deprotonation in the presence of an electrophile taking advantage of the high acidity of α-nitrile protons allowed examination of the effects of a chelating group on the nitrogen atom, a countercation, and the reactivity of an electrophile on the steric course. Analyses of reactions using aroyl chlorides and methyl iodide revealed the following: (1) the substitution reactions basically proceed with retention of configuration, (2) the extent of an inversion product increases with decreasing chelating ability of the N-substituent and with increasing leaving ability (ionic character) of a countercation (Li, Na, K) of the anionic species, and (3) the use of a more reactive electrophile results in an increase of the retention product.