Enantioselective Formation of 2-Azetidinones by Ring-Assisted Cyclization of Interlocked N-(α-Methyl)benzyl Fumaramides.

The synthesis of optically active interlocked and non-interlocked 2-azetidinones by intramolecular cyclization of N-(α-methyl)benzyl fumaramide [2]rotaxanes is described. Two different strategies of asymmetric induction were tested in which the chiral group was located either proximal or distal to the reacting center of the thread. During these experiments, an interesting equilibration process inside the macrocyclic void occurred, thus leading to the cyclization through the (α-methyl)benzyl carbon atom and giving rise to β-lactams, with a quaternary carbon atom, in an enantio- and diastereocontrolled manner. This cyclization also proceeds in kinetically stable chiral pseudo[2]rotaxanes, thus allowing further dethreading to provide enantioenriched 3,4-disubstituted trans-2-azetidinones. The stereochemical outcomes of the cyclizations inside and outside the macrocycle demonstrated noticeable differences.