Fluorohydrins from epoxide

Reeently, new fluorinating agents, tetrabutylphosphonium fluoride and its mono- and dihydrofluoride, were used for preparation of fluorohydrins from epoxides [14] (equation 13). 

Fluorohydrins from Epoxides with Anhydrous Hydrogen Fluoride General Procedurc ... 

Recently, silicon tetrafluoride [207] and tetrabutylphosphonium fluoride [208] have been used to prepare fluorohydrins from epoxides. Generation of a superacid is required for the ring opening of a perfluorinated oxirane [209] (Figure 3.42). 

Fluorohydrins 6 from Epoxides with Tetrabutylammonium Dihydrogen TVifluoride General Procedure ... 

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... 

Oxazolines.1 Reaction of 1,1-disubstituted epoxides with nitriles and SiF4 (1 equiv.) provides fluorohydrins, which oti further exposure to SiF4 are converted into 2-oxazolines, in which the nitrogen is attached to the substituted carbon. In the example cited, the yield is increased to 81% from reactions conducted at 80°. 

An early report describes the synthesis of fluorohydrins. in low yields, from simple epoxides with anhydrous hydrogen fluoride in diethyl ether containing some water. 1,2-Ep-oxycyclohexanc and 2,2-dimethyloxirane were opened to 2-fluorocyclohexanol in 14% yield and 2-fluoro-2-methylpropan-1 -ol in 20 % yield, respectively, by the same method, but these results could not be reproduced (see also Table 12), With acetonitrile as the solvent, simple epoxides are opened to the fluorohydrins.but yields are low due to side reactions such as oligomerization and rearrangement. 

Good yields of fluorohydrins 4/5 can be achieved even from simple aliphatic epoxides using 70 % hydrogen fluoridc/pyridine by careful control of the reaction conditions,but the regioselectivity may be considerably lower than with alkylamine hydrofliiorides. 

The reaction between epoxides and HF gives fluorohydrins and, generally, other products resulting from extensive polymerisation. However, the acidity and reactivity of HF may be decreased by the addition of a base, either an amine or KF, or by complexation with a Lewis acid, such as borontrifluoride etherate [174]. Consequently, pyridine-HF, Et3N-3HF [203] and -Pr2NH-3HF [204] efficiently cleave epoxides to give excellent yields of fluorohydrins (Figure 3.39). 

Phenaq l halides have featured in many published articles using CRED technology (typically en route to chiral epoxides) and the work by Gotor and coworkers demonstrate how enzymes can be used to make fluorohydrins 43 as shown in Scheme 6.16 using the CRED ADH-A from Rhodococcus ruber. 

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