SN2 versus E2 Competition of Cyclic Ethers

Our quantum chemical analyses reveal how the ring size of cyclic ethers has opposite effects on S_N2 and E2 pathways and thus on the S_N2/E2 competition. The preferred reaction pathway switches from E2, for large cyclic substrates, to S_N2, for small cyclic substrates.

Abstract

We have quantum chemically studied the influence of ring strain on the competition between the two mechanistically different S_N2 and E2 pathways using a series of archetypal ethers as substrate in combination with a diverse set of Lewis bases (F⁻, Cl⁻, Br⁻, HO⁻, H₃CO⁻, HS⁻, H₃CS⁻), 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_N2 pathway sharply decreases when the ring strain of the system is increased, thus on going from large to small cyclic ethers, the S_N2 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_N2, 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_N2 reaction.

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