Stereocontrolled synthesis of -lactams within [2]rotaxanes: a showcase of the chemical consequences of the mechanical bonding

Abstract

The intramolecular cyclization of N-benzyl fumaramide [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 differs from the common shielding stabilization of threaded functions through amide-based macrocycles promoting an unusual and disfavored 4-exo-trig ring closure. Further kinetic and synthetic studies allowed us to produce an original approach towards  -lactams through a one-pot protocol based on an intramolecular ring closure followed by a thermally-induced dethreading step. The advantages for carrying out this cyclization in the confined space of a benzylic amide macrocycle were attributed to the anchimeric assistance of the surrounding macrocycle.