The Role of Conformational Preorganization in the Reactivity of cis-1,2-Dimesylate-bis(benzyloxy)cyclooctane: An Activation Strain Perspective
ChemistryOpen, cilt.15, sa.7, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 15 Sayı: 7
- Basım Tarihi: 2026
- Doi Numarası: 10.1002/open.70251
- Dergi Adı: ChemistryOpen
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Chemical Abstracts Core, Compendex, EMBASE, MEDLINE, Directory of Open Access Journals, Academic Search Ultimate (EBSCO), Materials Science & Engineering Collection (ProQuest), Technology Collection (ProQuest)
- Anahtar Kelimeler: activation strain model analysis, aminocyclitols, azide, bis(benzyloxy)cyclooctane-1,2-diyl dimethanesulfonate, noncovalent interaction analysis
- Atatürk Üniversitesi Adresli: Evet
Özet
A computational study was performed to elucidate the factors governing the reactivity of a cis-substituted cyclooctane dimesylate toward sodium azide. The calculated energy profile reveals a clear kinetic preference for formation of the monosubstituted intermediate, while the second SN2 substitution is associated with a significantly higher activation barrier. Activation Strain Model (ASM) analysis indicates that this increase arises primarily from a larger distortion energy and less favorable interaction energy. Consistent with these findings, Non–Covalent Interaction (NCI) analysis reveals diminished stabilizing interactions and enhanced steric repulsion in the higher-energy transition state. Further analysis of the cyclooctane conformations demonstrates that the two pathways differ in their torsional distortion patterns. The lower-energy transition state proceeds through a more preorganized geometry, whereas the higher-energy pathway requires additional conformational reorganization to achieve the reactive arrangement of the leaving group. Together, these results establish conformational preorganization as a key factor governing reactivity in this flexible ring system.