Janus Face All‐cis 1,2,4,5‐tetrakis(trifluoromethyl)‐ and All‐cis 1,2,3,4,5,6‐hexakis(trifluoromethyl)‐ Cyclohexanes

• Published in: Angewandte Chemie International Edition Vol. 59; no. 45; pp. 19905 - 19909
• Main Authors: Yu, Cihang, Kütt, Agnes, Röschenthaler, Gerd‐Volker, Lebl, Tomas, Cordes, David B., Slawin, Alexandra M. Z., Bühl, Michael, O'Hagan, David
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 02-11-2020; John Wiley and Sons Inc
• Edition: International ed. in English
• Subjects: aryl hydrogenation; Communication; Communications; Conformation; Cyclohexane; cyclohexanes; Density; Electropositivity; Fluorides; Fluorine; Hydrogen storage; Iodides; Janus face; Stereochemistry; triaxial orientations; trifluoromethyl groups; aryl hydrogenation; Janus face; cyclohexanes; trifluoromethyl groups; triaxial orientations
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.202008662

We report the synthesis of all‐cis 1,2,4,5‐tetrakis (trifluoromethyl)‐ and all‐cis 1,2,3,4,5,6‐hexakis (trifluoromethyl)‐ cyclohexanes by direct hydrogenation of precursor tetrakis‐ or hexakis‐ (trifluoromethyl)benzenes. The resultant cyclohexanes have a stereochemistry such that all the CF3 groups are on the same face of the cyclohexyl ring. All‐cis 1,2,3,4,5,6‐hexakis(trifluoromethyl)cyclohexane is the most sterically demanding of the all‐cis hexakis substituted cyclohexanes prepared to date, with a barrier (ΔG) to ring inversion calculated at 27 kcal mol−1. The X‐ray structure of all‐cis 1,2,3,4,5,6‐hexakis(trifluoromethyl)cyclohexane displays a flattened chair conformation and the electrostatic profile of this compound reveals a large diffuse negative density on the fluorine face and a focused positive density on the hydrogen face. The electropositive hydrogen face can co‐ordinate chloride (K≈103) and to a lesser extent fluoride and iodide ions. Dehydrofluorination promoted decomposition occurs with fluoride ion acting as a base.
All‐cis 1,2,4,5‐tetrakis (trifluoromethyl)‐ and all‐cis 1,2,3,4,5,6‐hexakis (trifluoromethyl)‐ cyclohexanes were prepared by direct aryl hydrogenation. All‐cis 1,2,3,4,5,6‐hexakis(trifluoromethyl)cyclohexane has a high barrier to ring inversion (ΔG≠=27 kcal mol−1) and a Janus face profile with a large diffuse negative density on the fluorine face, and a focused positive density on the hydrogen face which coordinates carbonyls and halides.