Stereocontrolled Synthesis of β‑Lactams within [2]Rotaxanes: Showcasing the Chemical Consequences of the Mechanical Bond

The intramolecular
cyclization of N-benzyl­fumar­amide
[2]­rotaxanes is described. The mechanical bond of these substrates
activates this transformation to proceed in high yields and in a regio-
and diastereo­selective manner, giving interlocked 3,4-disubstituted trans-azetidin-2-ones. This activation effect markedly differs
from the more common shielding protection of threaded functions by
the macrocycle, in this case promoting an unusual and disfavored 4-exo-trig ring closure. Kinetic and synthetic studies allowed
us to delineate an advantageous approach toward β-lactams based
on a two-step, one-pot protocol: an intramolecular ring closure followed
by a thermally induced dethreading step. The advantages of carrying
out this cyclization in the confined space of a benzylic amide macrocycle
are attributed to its anchimeric assistance.