Fluorohydrin, formation

An alternative to fluorohydrin formation is observed with the 6/ -methyl-5a,6a-epoxide (30), which rearranges, possibly in a concerted reaction, to the A-homo-B-norsteroid (31) (cf, chapter 14, Vol. II). 

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

MibBtituent from axial to equatorial. On the other hand, this second effect iB not sufficient to offset the first with 8 - cetoxy-5j3,6j3 epoxy steroids. Finally, with respect to 3-oxo-G ,Qa.epoxidos, in wlikh mi furmational effect are negligible to a first approximation, the efeclron-withdrawing influence of the carbonyl dipole is die dominant directive factor, causing fluorohydrin formation exclusively. 

Boron trifluoride is commonly used as its diethyl etherate, but many commercial samples appear to contain fiuoroboric acid (HBF4) in equilibrium with BF3 + HF. The latter can apparently act as a source of fluoride ions and lead to epoxide-opening to form fluorohydrins. BFs-etherate which has been repeatedly purified by distillation behaves more nearly as a pure Lewis acid, and minimizes or eliminates fluorohydrin formation in most cases [3]. 

Opening of epoxides and aziridines. An observation that concerns the enantioselective opening of meyo-epoxides by SiC in the presence of 31 indicates a beneficial effect of the o-methoxy group to form an octahedral complex. " p-Titanoxy radical intermediates are involved when using 32 to open epoxides. A chiral Cr-salen complex has been used to mediate epoxide opening with KHFi. Although the ee values are moderate, this is the first report of fluorohydrin formation by such a method. " ... 

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... 

Rearrangements of ketones and aldehydes to difluoro-substituted ethers in the presence of hydrogen fluoride could be explained by the formation of fluorohydrin and further transformation to xenon fluoride ether, which readily decomposed90 and rearranged, thus forming difluoro ethers (Scheme 41). 

Although cyclization to three-membered rings is not as easy and as frequent as are cyclizations to six- and especially five-membered rings, it is not so uncommon with fluorinated compounds. In this particular case, the voluminous carbanion may cyclize easier than would with chlorine substituent for steric reasons. Precedents of such cyclizations are formations of ethylene oxide compounds from fluorohydrins [74]. 

Steric effects are presumably also responsible for the formation of pivalaldehyde (73) when (72) is treated with ether-free BF3 in CCI4 (equation 31). Although both isomers (E and Z) of (72) form pivalaldehyde as the major product under these conditions, a sharp distinction between the isomers was noted in ether solvent. Tlie ( )-isomer was recovered unchanged from conditions that with the (Z)-isomer gave fluorohydrin in good yield. ... 

The mechanism for the gas-phase reaction of trans-2,3-dideuterioethene oxide with HBr and HCl has been shown to involve anti ring-opening, with the formation of e fhro-R(CHD)2 0H (R = Cl or Br). The reaction of ethene oxide with HF followed a somewhat different course, affording only 5% of fluorohydrin together with (126) (37%) and oligomers and polymers. A possible mechanism for this reaction is shown (see Scheme 8) in which two moles of oxiran react with HF to give intermediate (125), which is open to polymerization with other oxiran molecules or to ring-expansion, with the subsequent formation of dioxane (126). 

Epoxide opening. Regioselective formation of fluorohydrins is observed. 

If the interaction of the a-oxide 340 with BF3-etherate is accompanied by a deep skeletal reconstruction, then a similar reaction with the dioxide 342 results in cis-fluorohydrine 343 with the carbon skeleton retained. In the latter case the homo-benzylic ion 344 does not seem to convert into a still more delocalized ion 345 (which would lead to skeleton rearrangement) since the development of the cation centre at C is hindered by the negative inductive effect of the oxygen of the endo-oxide cycle. Neither does the ion 344 admit any 1,2-hydride shift with the formation of ketone which indeed was not detected among the reaction products another test against the intermediate formation of a classical C -cation. 

The argument is closely analogous to that used to explain the regioselectivity of formation of bromoacetoxy compounds (Table 9.2) formed in the addition of bromine to alkenes in acetic acid. Similarly, addition of bromine to alkenes in water produces bromohydrins. Although they are more difficult to synthesize, iodohydrins and fluorohydrins are also known. For a review of the synthesis and reactions of halohydrins, see Rosowsky, A. in Weissberger, A., Ed. Heterocyclic Compounds with Three- and Four-Membered Rings, Part One Wiley-Intersdence New York, 1964 p.l. 

A soln. of 8-benzyloxy-2,6-dimethyl-2,3-epoxyoctane in ether added to /-Pr2NH and 4 eqs. H2O in the same solvent under a balloon of SiF4 at 0°, the mixture stirred for 1 h, then quenched with aq. KF -> 8-benzyloxy-2,6-dimethyl-2-fluorooctan-3-ol. Y 91%. The method is short and is undertaken with conventional glass apparatus olefins, ethers and 1,2-disubstd. oxiranes (aliphatic) were unaffected, while mono-subst. aliphatic oxiranes polymerized. Stereoselectivity is illustrated by the formation of 5y -fluorohydrins. F.e.s. M. Shimizu, H. Yoshioka, Tetrahedron Letters 29, 4101 (1988) l-fluoro-2-hydroxysilanes s. Tetrahedron Letters 30, 967-70 (1989). 

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