S_N 2 versus E2 Competition of Cyclic Ethers

We have quantum chemically studied the influence of ring strain on the competition between the two mechanistically different S_N 2 and E2 pathways using a series of archetypal ethers as substrate in combination with a diverse set of Lewis bases (F^- , Cl^- , Br^- , HO^- , H₃ CO^- , HS^- , H₃ CS^- ), using relativistic density functional theory at ZORA-OLYP/QZ4P. The ring strain in the substrate is systematically increased on going from a model acyclic ether to a 6- to 5- to 4- to 3-membered ether ring. We have found that the activation energy of the S_N 2 pathway sharply decreases when the ring strain of the system is increased, thus on going from large to small cyclic ethers, the S_N 2 reactivity increases. In contrast, the activation energy of the E2 pathway generally rises along this same series, that is, from large to small cyclic ethers. The opposing reactivity trends induce a mechanistic switch in the preferred reaction pathway for strong Lewis bases from E2, for large cyclic substrates, to S_N 2, for small cyclic substrates. Weak Lewis bases are unable to overcome the higher intrinsic distortivity of the E2 pathway and, therefore, always favor the less distortive S_N 2 reaction.