The all-syn isomer of 1,2,4,5-tetrafluorocyclohexane is prepared and characterised by NMR and X-ray crystallography. It emerges to be a particularly polar cyclohexane analogue with differentially polarised faces.

Preparation of the all-syn isomer of 1,2,3,4-tetrafluorocyclohexane is reported; X-ray structural studies shows a conformation with two of the C-F bonds oriented 1,3-diaxial to each other and (19)F-NMR reveals a through space diaxial (4)J(FF) coupling constant of 29 Hz.

A stereocontrolled synthesis of all-cis-1,2,4,5- tetrafluoro-3-phenylcyclohexane is developed as the first functionalised example of this polar cyclohexane motif. The dipolar nature of the ring, arising due to two 1,3-diaxial C-F bonds, is revealed in the solid-state (X-ray) structure. The orthogonal conformation of the aryl and cyclohexyl rings in all-cis-1,2,4,5-tetrafluoro-3-phenylcyclohexane, and in an ortho-nitro derivative, result in intramolecular (1h)JHF and (2h)JCF  NMR couplings relayed through hydrogen bonding. The aryl group of all-cis-1,2,4,5-tetrafluoro-3-phenylcyclohexane is elaborated in different ways to demonstrate the versatility of this compound for delivering the motif to a range of molecular building blocks.

Six of the best: Benzene had been used by Faraday and Mitscherlich in their respective synthesis of hexachloro‐ and hexabromocyclohexane in the early 19th century. Also starting from benzene, η‐1,2,3,4,5,6‐hexafluorocyclohexane (benzene hexafluoride; see X‐ray structure of a dimer) was now synthesized in five steps.

The original synthesis of all-cis 1,2,4,5,-tetrafluoro-2-phenylcyclohexane resulted in a trifluorocyclohexene as a significant co-product of the final fluorination step. This product was notable in that an elimination reaction was accompanied by C-F bond formation that had occurred with a retention of configuration. In order to deconvolute this reaction, the two isomers of the ditriflate diol precursor were separated, and they were each treated independently with Et3N·3HF. One gave the original all-cis 1,2,4,5,-tetrafluoro-2-phenylcyclohexane and the other the trifluorocyclohexene. A deuterium labeling experiment was carried out, resulting in a distribution of the isotope in the trifluorocyclohexene consistent with an intermediate (symmetrical) phenonium intermediate. Cognisant of this, a controlled elimination reaction of one of the diastereoisomers with DBU, followed by hydrogenation, gave a cyclohexane triflate, which, on fluorination, gave the all-cis 1,2,3-trifluoro-2-phenylcyclohexane now with an inversion of configuration.