The effective molarity (EM) puzzle in intramolecular ring-closing reactions

Ab initio and DFT calculations of thermodynamic and kinetic parameters for ring-closing reactions of bi-functional entities to form three-membered (1-11), four-membered (12-14), five-membered (15-28) and six-membered rings (29-31) reveal that the increase in demands on directional flexibility upon reducing the size of the ring, and the directional requirements of the nucleophilic orbitals have a profound effect on the rate of ring-closing reaction.