Allylic fluorides

The proximity of carbon-carbon double or triple bonds or a phenyl substituent, as in allylic, propargylic, or benzylic systems, has very little impact upon a fluorine substituent s chemical shift (Scheme 3.53). Note that one would not expect allyl fluoride and methallyl fluoride to have the same chemical shift. 

Related to the nitrile oxide cycloadditions presented in Scheme 6.206 are 1,3-dipolar cycloaddition reactions of nitrones with alkenes leading to isoxazolidines. The group of Comes-Franchini has described cycloadditions of (Z)-a-phenyl-N-methylnitrone with allylic fluorides leading to enantiopure fluorine-containing isoxazolidines, and ultimately to amino polyols (Scheme 6.207) [374]. The reactions were carried out under solvent-free conditions in the presence of 5 mol% of either scandium(III) or indium(III) triflate. In the racemic series, an optimized 74% yield of an exo/endo mixture of cycloadducts was obtained within 15 min at 100 °C. In the case of the enantiopure allyl fluoride, a similar product distribution was achieved after 25 min at 100 °C. Reduction of the isoxazolidine cycloadducts with lithium aluminum hydride provided fluorinated enantiopure polyols of pharmaceutical interest possessing four stereocenters. 

The first additions to a fluoro-ene were of chlorine and bromine to the C = C bond of allyl fluoride. Meslans used silvcr(I) fluoride, arsenic(III) fluoride, zinc(II) fluoride and antimony(III) fluoride to convert21 acetyl chloride to the fluoride, which was shown to have a reactive C — F bond. The first reaction on a saturated fluoride to retain the C —F link was by Collie.22 Tetramethylammonium fluoride was transformed to fluoromethane on heating which was then converted to chlorofluoromethane by treatment with chlorine. 

Cyclopropyl silyl ethers undergo ring opening to give allylic fluorides when treated with DAST at room temperature (see Table 5).35... 

Conversion of Cyclopropyl Silyl Ethers to Allylic Fluorides General Procedure 55... 

In allyl fluorides, substitution of fluorine can proceed virtually according to an SN2 mechanism. Actually, this substitution is more likely a stepwise reaction with addition of an amine and subsequent elimination of fluoride to form a shifted double bond.11 14... 

Syn selectivity in the epoxidation of allylic fluorides by peracids has been interpreted by electronic stabilization of the transition state with the electronegative fluorine atom oriented at the inside position304. 

Molecular-orbital calculations indicate that the stereoselective epoxidation of the alkene 192 by peroxy acids arises from stereoelectronic control exerted by a CF3— C bond orientated anti to the alkene plane, in contrast to the previously proposed model for epoxidation of allylic fluoride in which the F—C bond and alkene bonds are in a syn arrangement305. 

It is worth noting that the same kind of dramatic hyperconjugative tz—oCF interactions that were observed for substituted benzyl fluorides (see Section 2.2.1) are also apparently in play here. The observed trends for the two series of allyl fluorides in Scheme 3.70 show this to be clearly the case. 

Allylic alcohols 8 may be transformed into the rearranged allyl fluorides 9 by means of an S Mi or S, 2 mechanism." ... 

Solvolysis of allylic fluorides may be acid-catalysed [35] and the influence of fluorine substituents at different positions is interesting. Solvolysis of 5.15A occurs where fluorine at the 1-position is able to stabilise an attached carbocation but in the isomer 5.15B fluorine at the 2-position deactivates and solvolysis of 5.15B does not occur under conditions where 5.15A reacts (Figure 5.15). Similar hydrolysis of 1,2-diethoxytetrafluorocyclobutene leads to the well-known, very stable, squarate anion [36] (Figure 5.16a). 

Allyl fluoride is also reported to undergo halogen exchange with B2CI4 vide infra). 

Excess allyl fluoride is reported to react vigorously with B2CI4 at —80° C to produce a product mixture including BCI3, BFj, B2F4, and allyl chloride (23). The reaction is thus similar to the B2Cl4-fluoroolefin reactions mentioned previously. 

As expected, the influence of the halogen in a-halo ketones strongly influences the course of the reaction. At — 10°C, 2-chlorocyclohexanone reacted with pyrrolidine to give the isolable intermediate amino-substituted allylic chloride 6 (X = Cl) in 85% yield, along with 15% of bicyclic aminal. The corresponding a-bromo ketone showed the expected tendency for further ring closure into the cyclopropanone aminal 7, while a-fluorocyclohexanone was completely transformed into the allylic fluoride 6 (X = F). ... 

Allylic fluoride can be obtained from siloxycyclopropanes and diethylaminosulfur trifluoride in good yields. Allylic cations may play a key role in this reaction. 

Allylic fluorides are obtained with silver(I) fluoride in acetonitrile. ... 

HH and Vhf couplings have been measured by Gree et for a series of allylic fluorides and for the products of the Diels-Alder addition of these compounds to butadienes. The experimental coupling values have been subsequently compared with the couplings calculated for the predicted conformers of the compounds under study. This procedure allowed the authors to establish the conformational preferences in both groups of compounds. 

Both the conversion of 2,2,2-trifluoroethanesulfonates into mesylates, and the reductive allylation of dithio esters and trithio carbonates with allyl fluoride are mediated by TBAF. It is also used to promote silylation of alcohols by silazines or hydrosilanes or disilanes. 

Allylic fluorides. Ring cleavage attends the treatment of tertiary cyclopropyl silyl... 

In allyl fluoride the fluorine eclipses the double bond, but in allyl chloride and bromide the gauche conformations are preferred to the extent of 82 and 95% respectively (Schei and Shen, 1985 Schei, 1983). In a-haloacid halides, such as chloroacetyl chloride, analogous conformations with the halogen atom eclipsed by the carbonyl have been found to be the most stable conformer (Nakagawa et al., 1952). The energy difference between s-tram... 

One allylic fluoride isomerization has been studied kinetically. Solvolysis of 1,3,5,7,7,7-hexafluoro-l-heptene in 97.3% formic acid, viz-... 

The HF and /hh couplings have been found to be a reliable criterion m establishing the regiochemistry and stereochemistry of a few [l-fluoroalkyl]-3-ethyl-2-isoxazolines obtained by the cycloaddition of nitrile oxides to some allylic fluorides and of individual regioisomeric and tautomeric pairs of H(CF2)2-containing isoxazoles and pyrazoles. ... 

Lentz and coworkers reported that air-stable titanocene difluoride can act as a catalyst for hydrodefluorination reactions in the presence of silane derivatives, giving excellent yields even at low temperature. The authors expanded the scope of the reaction to other substrates such as vinylic and allylic fluorides and a range of catalysts.Mechanistic studies indicated that a titanium(m) hydride is the active species, and the silane derivative is the hydride source. This catalytic system is not only interesting form the environmental point of view, but also for the synthesis of new organic molecules as it represents a new synthetic route to obtain inaccessible aminopyridine derivatives." ... 

Figure 6.31 The relative importance of different eclipsed conformations in substituted allyl fluorides. (Source Qiu 2011 (52). Reproduced with permission of John Wiley and sons.)...

Qiu Y, Han, D. (2011). Substituent effects on the conformational stability of allyl fluorides. Journal of Physical Organic Chemistry, 24, 431. 

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