Hydrogen fluoride with epoxides

In combination with aluminum Irifluoride, an increase in reactivity of potassium and sodium hydrogen fluoride towards epoxides is observed. " The reaction can be further accelerated by ultrasonic irradiation. From the product distribution it can be assumed that the mechanism of the ring opening under these conditions is dilTercnt from the reaction with potassium hydrogen fluoride alone. Probably a reaction between the hydrogen difluoride salt and aluminum trifluoride takes place with liberation of hydrogen fluoride in situ. This method is, therefore, more related to those discussed in Section 1.1.4.3.2.1.1. 

Several cortisone derivatives with glucocorticoid effects are most active, if they contain fluorine in the 9or-position together with an Il(9-OH group. Both substituents are introduced by the cleavage of a 9,11 -epoxide with hydrogen fluoride. The regio- and stereoselective formation of the -epoxide is achieved by bromohydrination of a 9,11-double bond and subsequent alkali treatment (J. Fried, 1954). 

Epoxide Opening with Hydrogen Fluoride in Chloroform-Ethanoi... 

Fluorohydrin formation by epoxide opening with hydrogen fluoride in chloroform-ethanol, 433... 

Rearrangement of fluorine with concomitant ring opening takes place in fluorinated epoxides Hexafluoroacetone can be prepared easily from perfluo-ropropylene oxide by isomerization with a fluorinated catalyst like alumina pre treated with hydrogen fluoride [26, 27, 28] In ring-opening reactions of epoxides, the distribution of products, ketone versus acyl fluoride, depends on the catalyst [29] (equation 7) When cesium, potassium, or silver fluoride are used as catalysts, dimenc products also are formed [29]... 

More recent work in the corticosteroid senes has involved modification of the dihydrox-yacetone side chain at the 17 position Activity is retained, for example, when the hydroxyl group at the 17 position is omitted Thus, addition of the elements of hypobromous acid to tnene 36 [8], gives the bromohydnn 37, treatment with base leads to internal elimination to form the p-epoxide 38, opening of the oxir.ine with hydrogen fluoride gives desoximetasone, 39, [9]... 

Fluorohydrins.1 Both this reagent (1) and Olah s pyridinium poly (hydrogen fluoride) (2) serve as an attenuated source of hydrogen fluoride, and both convert simple epoxides into fluorohydrins, but reactions with 1 require higher temperatures than those with 2. The two reagents can differ in the regioselectivity, with steric factors being more important in reactions of 1 than those of 2. 

Fluorine at the equatorial 6a position also results in an increase in potency. One scheme for the production of such a compound relies on the shift of the double bond from the 4,5 to the 5,6 position, which follows the formation of an acetal at position 3. The scheme starts with the selective reduction of the 11 ketone in the cortisone intermediate (13-2). Epoxidation of the product (18-1) with a peracid takes place selectively at the unconjugated double bond to give the 5a,6a oxirane (18-2). Treatment of that with hydrogen fluoride in tetrahydrofuran leads to fluorohydrin (18-3). (There is evidence to indicate that the reagent involves an HF THF acid base complex since the omission of THF in at least some cases leads to a complex mixture of rearrangement products [15].) The side chain in fluorohydrin (18-3) is then converted... 

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