Stepwise preparation of all-cis 1,3,4-trifluoro-2-phenylcyclohexane, avoiding a phenonium intermediate

The original synthesis of all-cis 1,2,4,S,-tetrafluoro-2-phenylcyclohexane resulted in a trifluorocydohexene 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 trifluorocydohexene. 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 cydohexane triflate, which, on fluorination, gave the all-cis 1,2,3-trifluoro-2-phenylcyclohexane now with an inversion of configuration.