Allyl fluoride, addition

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. 

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... 

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. 

Sodium hydride removes a proton from the sulfone to give an anion that can act as a nucelophile. Displacement of mesylate gives an allyl silane, which is converted into an allyhc anion by fluoride. Addition to the ketone gives a 5/5 fused system with the more stable cis ring junction. 

All the products from the reactions of ltf,2fl -octafluorocyclohexene, -hexafluorocyclopentene, and -tetrafluorocyclobutene with methoxide ion in methanol are consistent with a mechanism involving addition of methoxide ion and elimination of fluoride ion, with no direct displacement of allylic fluoride. Thus, with the least reactive cyclohexene (36), the products (37)—(40) are consistent with the mechanism shown in Scheme 16. Under the conditions of the reaction, methoxyc clohexene (38) is converted into methoxycyclohexene (39) by proton migration. 

Now we have examined several different allylsilicates in the allylation of aldehydes. The most reactive allylsilicate is tetrafluorosilicates derived by fluoride addition to allyltrifluo-rosilane. The least reactive one is derived by the Martin s ligand which did not react at all with aldehydes. Bis(diolato)allylsilicates are next inactive. Inversely, bis(diolato)silicates are most selective, since they react only with aryl aldehydes. This interesting reactivity and selectivity relationship may be correlated with the increasing Lewis acidity of pentacoordinate allylsilicates. The steric factors are also important. The most Lewis-acidic tetrafluoroallylsilicates are sterically least hindered. Therefore, it is not easy to distinguish two factors at this moment. However, the importance of the Lewis acidity of the silicon centers is definitely demonstrated by the stereoselection. 

Torgov introduced an important variation of the Michael addition allylic alcohols are used as vinylogous a -synthons and 1,3-dioxo compounds as d -reagents (S.N. Ananchenko, 1962, 1963 H. Smith, 1964 C. Rufer) 1967). Mild reaction conditions have been successful in the addition of ],3-dioxo compounds to vinyl ketones. Potassium fluoride can act as weakly basic, non-nudeophilic catalyst in such Michael additions under essentially non-acidic and non-basic conditions (Y. Kitabara, 1964). 

So far, there is no conclusive evidence that a free allyl carbanion is generated from allylsilanes under fluoride ion catalysis. A hypervalent silyl anion, with the silicon still bonded to the allylic moiety, accounts equally well for the results obtained. Based on a variety of experimental results, it is in fact more likely that a nonbasic hypervalent silyl anion is involved rather than the basic free allyl carbanion first postulated14-23. When allylsilanes are treated with fluoride in the presence of enones. 1,4-addition takes place along with some 1,2-addition13. 

Therefore, in order to obtain a 1,4-addition of an allyl residue to an enone, two activation modes can be used reactions take place either under electrophilic conditions with Lewis acid promotion, or in the presence of fluoride ions. This is important as the stereochemical outcome often depends on the activation mode selected. 

Allyl tetrafluoroborates are also useful allylboration reagents. They can be made from allylic boronic acids and are stable solids.63 The reaction with aldehydes is mediated by BF3, which is believed to provide the difluoroborane by removing a fluoride. The addition reactions occur with high stereoselectivity, indicating a cyclic TS. 

Some examples of conjugate addition reactions of allylic silanes are given in Scheme 9.5. Entries 1 to 3 illustrate the synthesis of several (3-allyl ketones. Note that Entry 2 involves the creation of a quaternary carbon. Entry 4 was used in the synthesis of a terpenoid ketone, (+)-nootkatone. Entry 5 illustrates fluoride-mediated addition using tetrabutylammonium fluoride. These conditions were found to be especially effective for unsaturated esters. In Entry 6, the addition is from the convex face of the ring system. Entry 7 illustrates a ring closure by intramolecular conjugate addition. 

B. Potassium allyl- and crotyltrifluoroborates undergo addition to aldehydes in biphasic media as well as water to provide homoallylic alcohol in high yields (>94%) and excellent diastereoselectivity (dr >98 2). The presence of a phase-transfer catalyst (e.g., B114NI) significantly accelerates the rate of reaction, whereas adding fluoride ion retards the reaction (Eq. 8.70).165 The method was applied to the asymmetric total synthesis of the antiobesity agent tetrahydrolipstatin (orlistat).166... 

When carried out under standard conditions with Et3SiH/TFA, reduction of acrolein leads to a mixture of allyl alcohol, 1-propanol, and di-n-propyl ether in addition to allyl trifluoroacetate and -propyl trifluoroacetate.434 The 1,2-reduction of cinnamaldehyde with triethoxysilane in the presence of fluoride ion provides the corresponding allyl alcohol in good yields (Eq. 261). 

Cyclization reactions of vinyl- and alkynylsilanes have been reviewed100. The course of the reaction of the cyclohexenone derivative 184 depends on the catalyst employed ethylaluminium dichloride gives solely the product 185 of 1,6-addition, whereas tetrabuty-lammonium fluoride yields a mixture containing 69% of the 1,4-adduct 186 and 31% of the bridged compound 187 (equation 89)101. Intramolecular addition reactions of allylic silanes102 may also be catalysed by Lewis acids (equation 90) or fluoride ions, and in this case an allyl anion or a pentavalent silicon intermediate may be involved (equation 91). Such reactions are exemplified by the formation of a 1 5 mixture of the diastereomers 189 and 190 when the cyclohexenone derivative 188 is treated with ethylaluminium dichloride (equation 92). In the presence of fluoride anion the ratio of the isomers is reversed103. 

Carbanions, generated by the reaction of benzylsilanes with tetra-n-butylammo-nium fluoride react with non-enolizable aldehydes to produce the alcohol [67], When a stoichiometric amount of the ammonium fluoride is used, the methylarene corresponding to the benzylsilane is frequently a by-product and arises from formation of the hydrogen difluoride salt during the reaction. When only catalytic amounts of the ammonium fluoride initiate the reaction, the formation of the methylarene is suppressed. In a similar type of reaction (although the mechanism is not known) between aldehydes and ketones, allyl bromide, and tin in the presence of trimethylsilyl chloride the yield of the but-l-en-4-ol is raised significantly by the addition of tetra-n-butylammonium bromide, particularly in the reactions with... 

Nitroalkanes react with Jt-deficient alkenes, for example, p-nitro ketones are produced from a,P-unsaturated ketones [41], whereas allylic nitro compounds have been prepared via the Michael-type addition of nitroalkanes with electron-deficient alkynes (Table 6.19). The reaction in either dimethylsulphoxide [42] or dimethyl-formamide [43] is catalysed by potassium fluoride in the presence of benzyltriethyl-ammonium chloride the reaction with dimethyl acetylenedicarboxylate is only successful in dimethylsulphoxide [42], Primary nitroalkanes produce double Michael adducts [42,44], A-Protected a-aminoacetonitriles react with alkynes under catalysed solidiliquid conditions to produce the Michael adducts [45] which, upon treatment with aqueous copper(Il) sulphate, are converted into a,p-unsaturated ketones. 

Allyltin difluoroiodide, formed in situ by the oxidative addition of stannous fluoride to allyl iodide, is found to react with carbonyl compounds to give the corresponding homoallylic alcohols in excellent yields under mild reaction conditions (9). 

Unsaturated fluorinated compounds are fundamentally different from those of hydrocarbon chemistry. Whereas conventional alkenes are electron rich at the double bond, fluoroal-kenes suffer from a deficiency of electrons due to the negative inductive effect. Therefore, fluoroalkenes react smoothly in a very typical way with oxygen, sulfur, nitrogen and carbon nucleophiles.31 Usually, the reaction path of the addition or addition-elimination reaction goes through an intermediate carbanion. The reaction conditions decide whether the product is saturated or unsaturated and if vinylic or allylic substitution is required. Highly branched fluoroalkenes, obtained from the fluoride-initiated ionic oligomerization of tetrafluoroethene or hexafluoropropene, are different and more complex in their reactions and reactivities. 

Addition of allyl alcohol to perfluoro(2-mcthy1propene) in the absence of a catalyst gave ally ether 2 and rearranged ester 4, presumably formed by alcoholysis of the intermediate acyl fluoride 3. 

Methyl perfluoromethacrylate reacts with allyl and propargyl alcohols to give the Michael addition products 19 and 20, respectively these eliminate hydrogen fluoride in the presence of the boron trifluoride-triethylamine complex and rearrange to acyl fluorides 21 and 22. Hydrolysis of the acyl fluorides with base results in decarboxylation to give the 2-(trifluoromethyl) esters 23 and 24.11... 

A nucleophilic mechanism can be applied in reductions with complex hydrides of highly fluori-nated aliphatic and alicyclic fluoroalkenes with electron-deficient C = C bonds the hydride anion adds as a strong nucleophilic agent to the more electrophilic carbon atom the intermediate anion can then lose a fluoride ion either from the original C = C bond, or from the allylic position finishing an SN2 displacement of the fluorine. Thus, the reductions of vinylic C-F bonds with hydrides proceed by a nucleophilic addition-elimination mechanism. Displacement of fluorine in highly fluorinated aromatic compounds proceeds by the same mechanism ... 

Tnfluoromethyl groups are very resistant to hydrolysis, unless they are allylic or benzylic, or vicinal to a carbon linked to hydrogen. In the last case, elimination of hydrogen fluoride leads to the formation of a difluoromethylene group which is key to additional reactions... 

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