Regio and stereochemical probes of iodine interactions in diiodocyclododecanes

Cyclododecane preferentially adopts a square-like geometry, giving rise to corner and edge methylene (CH2) groups, whose hydrogens assume different orientations. In edge CH2 groups, hydrogens can be inward- (endo) and outward-looking (exo) the ring. Herein, we have quantum-chemically studied the replacement of two hydrogens in cyclododecane with iodines at the relative positions 1,4, 1,5, 1,6, and 1,7. Intramolecular interactions are only slightly unfavorable in 1,7-diiodocyclododecane containing the organic iodines in the edge/endo positions, less than expected from steric considerations. This behavior was discussed in terms of transannular interactions, and a numerical estimation for the magnitude of the intramolecular interaction energy has been performed based on an isodesmic reaction scheme and by natural energy decomposition analysis. 1,5-Diiodocyclododecane with both edge iodines in the endo orientation (occupying opposite faces of the ring) is strongly favored (by ca. 2.0 kcal mol(-1)) compared to the respective monosubstituted counterparts, due to highly stabilizing hyperconjugative interactions. Although halogen bonding involving anionic species is widely known, we show that organic halogens, in particular iodine, can be useful for stereochemical control in macrocycles.

Automated summary

The study reveals that replacing two hydrogen atoms in cyclododecane with iodine atoms can affect intramolecular interactions and stability, particularly in 1,7-diiodocyclododecane. Additionally, 1,5-diiodocyclododecane exhibits strong stability due to hyperconjugative interactions within the ring. This suggests that organic halogens, such as iodine, can play a role in stereochemical control in macrocycles.