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Chem."],"accepted":{"date-parts":[[2019,3,20]]},"abstract":"<jats:p>The presence of strong stereoelectronic interactions involving the substituents in <jats:italic>cis<\/jats:italic>-2-substituted cyclohexanes may lead to results different from those expected. In this work, we studied the conformational behavior of <jats:italic>cis<\/jats:italic>-2-fluoro- (<jats:bold>F<\/jats:bold>), <jats:italic>cis<\/jats:italic>-2-chloro- (<jats:bold>Cl<\/jats:bold>), <jats:italic>cis<\/jats:italic>-2-bromo- (<jats:bold>Br<\/jats:bold>) and <jats:italic>cis<\/jats:italic>-2-iodocyclohexylamine (<jats:bold>I<\/jats:bold>) by dynamic NMR and theoretical calculations. The experimental data pointed to an equilibrium strongly shifted toward the <jats:bold>ea<\/jats:bold> conformer (equatorial amine group and axial halogen), with populations greater than 90% for <jats:bold>F<\/jats:bold>, <jats:bold>Cl<\/jats:bold> and <jats:bold>Br<\/jats:bold> in both dichloromethane-<jats:italic>d<\/jats:italic><jats:sub>2<\/jats:sub> and methanol-<jats:italic>d<\/jats:italic><jats:sub>4<\/jats:sub>. Theoretical calculations (M06-2X\/6-311++G(2df,2p)) were in agreement with the experimental, with no influence of the solvent or the halogen on the equilibrium. A principal component analysis of natural bond orbital energies pointed to the \u03c3*<jats:sub>C\u2013X<\/jats:sub> and \u03c3<jats:sub>C\u2013H<\/jats:sub> orbitals and the halogen lone pairs (LP<jats:sub>X<\/jats:sub>) as the most significant for the hyperconjugative interactions that influenced the equilibrium. The \u03c3<jats:sub>C\u2013H<\/jats:sub> \u2192 \u03c3*<jats:sub>C\u2013X<\/jats:sub> hyperconjugation and the interactions involving the LP<jats:sub>X<\/jats:sub> counterbalance each other, explaining the non-influence of the halogen on the conformational equilibrium. These interactions are responsible for the strong preference for the <jats:bold>ea<\/jats:bold> conformer in <jats:italic>cis<\/jats:italic>-2-halocyclohexylamines, being strong enough to restrain the shift in the equilibrium due to other factors such as steric repulsion or solvent effects.<\/jats:p>","DOI":"10.3762\/bjoc.15.79","type":"journal-article","created":{"date-parts":[[2019,4,1]],"date-time":"2019-04-01T09:17:47Z","timestamp":1554110267000},"page":"818-829","source":"Crossref","is-referenced-by-count":6,"title":["Strong hyperconjugative interactions limit solvent and substituent influence on conformational equilibrium: the case of <i>cis<\/i>-2-halocyclohexylamines"],"prefix":"10.3762","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6274-3948","authenticated-orcid":false,"given":"Camila 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