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

Alastair J. Durie, Tomoya Fujiwara, Nawaf Al-Maharik, Alexandra M. Z. Slawin, David O'Hagan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)8228-8233
Number of pages6
JournalThe Journal of Organic Chemistry
Volume79
Issue number17
Early online date7 Aug 2014
DOIs
Publication statusPublished - 5 Sept 2014

Fingerprint

Dive into the research topics of 'Stepwise preparation of all-cis 1,3,4-trifluoro-2-phenylcyclohexane, avoiding a phenonium intermediate'. Together they form a unique fingerprint.

Cite this