Iodine Gauche Effect Induced by an Intramolecular Hydrogen Bond

Abstract

The gauche conformer in 1-X,2-Y-disubstituted ethanes, that is, the staggered orientation in which X and Y are in closer contact, is only favored for relatively small substituents that do not give rise to large X···Y steric repulsion. For more diffuse substituents, weakly attractive orbital interactions between antiperiplanar bonds (i.e., hyperconjugation) cannot overrule the repulsive forces between X and Y. Our quantum chemical analyses of the rotational isomerism of XCH2CH2Y (X = F, OH; Y = I) at ZORA-BP86-D3­(BJ)/QZ4P reveal that indeed the anti conformer is generally favored due to a less destabilizing I···F and I···O–H steric repulsion. The only case when the gauche conformer is preferred is when the hydroxyl hydrogen is oriented toward the iodine atom in the 2-iodoethanol. This is because of the significantly stabilizing covalent component of the I···H–O intramolecular hydrogen bond. Therefore, we show that strong intramolecular interactions can overcome the steric repulsion between bulky substituents in 1,2-disubstituted ethanes and cause the gauche effect. Our quantum chemical computations have guided nuclear magnetic resonance experiments that confirm the increase in the gauche population as X goes from F to OH.

Conformational Landscape of α-Halopropiophenones Determined by nJC–H NMR Reveals Unexpected Patterns and Geometric Constraints

“…However, even for the bulky iodine, the insertion of a stabilizing component, such as a hydrogen bond, is enough to overcome sterics and shift the equilibrium toward the gauche conformer in 2-iodo-ethanol. 4 In α-halogenated ketones, the effect of the halogen can be even more dramatic, although hyperconjugation is known to generally play an important role, due to the carbonyl π* orbital ability to accept electron density. 5 This effect was observed by Olivato and co-workers in α-halogenated acetophenones, where the O�C−C−X dihedral angle changes in proportion to the increase in the halogen size to maximize the orbital overlap responsible for the interaction.…”

“…In this example, the steric effects become larger as the halogen size increases. However, even for the bulky iodine, the insertion of a stabilizing component, such as a hydrogen bond, is enough to overcome sterics and shift the equilibrium toward the gauche conformer in 2-iodo-ethanol …”