“…It should be noted that with the exception of these inherently restricted ring systems, − at present, it is not clear if N-pyramidalization alone is sufficient to engender new reactivity of amide bonds. − In this respect, the case of bridged lactams is instructive; it has been shown in several studies that properties of twisted bridged lactams can be correlated with both twist and nitrogen pyramidalization when (1) comparing amide distortion within the same classes of N -alkyl nonplanar bridged amides, and (2) the amide bond is sufficiently geometrically altered to promote N -amino-ketone type reactivity. ,,,, By contrast, electronic activation by N -acyl or related substitution leads to redistribution of the nitrogen lone pair into the activating substituent, − which in turn disconnects the amide bond conjugation within the N–C(O) moiety and results in N lp being engaged in another n N to π* XO delocalization.…”