Durie Alastair J, Fujiwara Tomoya, Al-Maharik Nawaf, Slawin Alexandra M Z, O'Hagan David
University of St. Andrews , EastChem School of Chemistry, North Haugh, St. Andrews, KY16 9ST, U.K.
J Org Chem. 2014 Sep 5;79(17):8228-33. doi: 10.1021/jo501432x. Epub 2014 Aug 19.
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.
全顺式1,2,4,5-四氟-2-苯基环己烷的最初合成过程中，在最终氟化步骤产生了一种三氟环己烯作为重要的副产物。该产物值得注意的是，消除反应伴随着构型保持的C-F键形成。为了剖析该反应，分离了二磺酸二醇前体的两种异构体，并分别用Et3N·3HF独立处理。一种得到了原始的全顺式1,2,4,5-四氟-2-苯基环己烷，另一种得到了三氟环己烯。进行了氘标记实验，结果表明三氟环己烯中的同位素分布与中间体（对称）苯鎓中间体一致。基于此，其中一个非对映异构体与DBU进行受控消除反应，然后氢化，得到环己烷三氟甲磺酸酯，该产物在氟化时得到了构型翻转的全顺式1,2,3-三氟-2-苯基环己烷。
