Effect of the character of the N-substituent in 4-piperidones on the stereochemistry of phenyllithium synthesis

An analysis of the stereochemical structure‐activity relationships of C‐methyl derivatives of the reversed ester of meperidine

“…The conformation (23) may seem unlikely as the active (receptor-bound) form of the molecule since it requires 3 axial substituents in comparison with the single axial phenyl of (22). However, not only is the equatorial 4-phenyl chair (with axial Me and OCOEt substituents) preferred to the axial 4-phenyl chair conformation of P-prodine, it is also favored in the case of the y-2,3-dimethyl analog of promedol (24) and the corresponding 4-piperidinol hydro-~h l o r i d e .~' ,~~ Antipodal forms of y- (24) have not yet been examined, but the racemic mixture is about four times as potent as the reversed ester of 4s Isomer 4R Isomer meperidine and 100 times that of P- (24). It is highly probable that the 4s isomer will prove the more active antipode, and it follows that the receptor can accommodate axial methyl adjacent to nitrogen within either enantiotropic edge [cf.…”