Triple Thorpe-Ingold Effect in the Synthesis of 18-Membered C3 Symmetric Lactams Stacking as Endless Supramolecular Tubes

Chemistry. 2023 Mar 1;29(13):e202203717. doi: 10.1002/chem.202203717. Epub 2023 Jan 26.


Three C3 symmetric macrolactams were very efficiently cyclized from their linear precursors. Adequately located substituents are responsible for the enhancement of reactivity that is not observed in the unsubstituted parent. DFT calculations show that the properly folded cyclization precursor, the reactive conformer, is more populated than other conformers, leading to a decrease of free energy of activation. The crystal structure of the ring substituted with three very bulky esters indicates that tubular stacking is preserved.

Keywords: crystals; macrocyclization; macrolactams; nanotubes; supramolecular chemistry.