Selective Fluorination of Steroids Using Elemental Fluorine

Shlomo Rozen, Giora Ben-Shushan

Research output: Contribution to journalArticlepeer-review

Abstract

Elemental fluorine, when diluted with nitrogen, replaces tertiary deactivated hydrogens via the extremely rare electrophilic substitution on a saturated sp3 carbon. This work describes such substitutions on steroids including the cases of the less common 3α-ol and 5β series. Depending on the location of the deactivating oxygenated functions in the steroid one can direct the substitution on any of the tertiary 5, 9, 14,17, or 25 positions. A full retention of configuration is observed, in accordance with the proposed substitution mechanism. One of the major differences between the 3α- and the 3β-sterols is the fact that in the latter series we have never witnessed fluorination at the 5 position, while in the 3α-ol derivatives the formation of the 5C-F bond is quite common. A second difference between the 5α- and the 5β-steroids concerns the fluorination of the electronically favorable 9 position. In the 5β series the A/B cis arrangement sterically prevents the approach to this position so the 9C-H bond remains untouched. Some leads are also presented as to the question whether or not this reaction can be carried out efficiently at higher than the usual -75 °C. CNDO calculations, coupled with the MM1 program, offer good criteria as to which single tertiary site of the few present will be substituted by the fluorine atom.

Original languageEnglish
Pages (from-to)3522-3527
Number of pages6
JournalJournal of Organic Chemistry
Volume51
Issue number18
DOIs
StatePublished - 1986

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