Esters unsaturated, fluorination

Because of thetr electron deficient nature, fluoroolefms are often nucleophihcally attacked by alcohols and alkoxides Ethers are commonly produced by these addition and addition-elimination reactions The wide availability of alcohols and fliioroolefins has established the generality of the nucleophilic addition reactions The mechanism of the addition reaction is generally believed to proceed by attack at a vinylic carbon to produce an intermediate fluorocarbanion as the rate-determining slow step The intermediate carbanion may react with a proton source to yield the saturated addition product Alternatively, the intermediate carbanion may, by elimination of P-halogen, lead to an unsaturated ether, often an enol or vinylic ether These addition and addition-elimination reactions have been previously reviewed [1, 2] The intermediate carbanions resulting from nucleophilic attack on fluoroolefins have also been trapped in situ with carbon dioxide, carbonates, and esters of fluorinated acids [3, 4, 5] (equations 1 and 2)... 

Various /i-oxo esters are fluorinated by perchloryl fluoride in the presence of sodium ethoxide, while the fluoro products 8 are usually converted into a-fluoro esters 9 various saturated and unsaturated long-chain esters, e.g. 10 and 11, can be prepared in high yield.23-24... 

Hunger, K., Epoxidation of a,P-unsaturated phosphonic acid esters, Chem. Ber., 101, 3530, 1968. Kadyrov, A.A., Rokhlin, E.M., and Knunyants, LL., Epoxidation of highly electrophilic unsaturated fluorine-containing compounds by peracids, Izv. Akad. Nauk SSSR, Ser Khim., 2344,1982 Bull. Acad. Sci. USSR, Div. Chem. Sci. (Engl. Transl.), 2063, 1982. 

This topic has been reviewed [2, pp 94, 100-111, 130-134] All of the standard approaches to the synthesis of a compound like methyl 2-fluorostearate from methyl 2-bromostearate result mall yield of the 2-fluoro ester and the unsaturated esters. Although silver fluoride is not a new reagent, its use moist in wet acetonitrile to convert methyl 2-bromostearate to its fluoro ester is a departure from the traditional set of anhydrous conditions (Procedure 6, p 194) [71] In contrast, silver tetrafluoroborate converts a-chloroketones to their respective fluoroketones under anhydrous conditions. The displacement of less activated halogen groups by silver tetrafluoroborate to form their respective fluorides is novel Although silver tetrafluoroborate could not be used to convert an aliphatic terminal dichloromethyl or trichloromethyl group to its corresponding fluoro derivative, it is an effective fluorine source in other situations [72] (Table 8)... 

Table 3 summarizes the scope and limitation of substrates for this hydrogenation. Complex 5 acts as a highly effective catalyst for functionalized olefins with unprotected amines (the order of activity tertiary > secondary primary), ethers, esters, fluorinated aryl groups, and others [27, 30]. However, in contrast to the reduction of a,p-unsaturated esters decomposition of 5 was observed when a,p-unsaturated ketones (e.g., trans-chalcone, trans-4-hexen-3-one, tra s-4-phenyl-3-buten-2-one, 2-cyclohexanone, carvone) were used (Fig. 3) [30],... 

When R2 substituent is flourocontaining alkyl group, the transformation 17 18 becomes hindered and its proceeding requires some special methods. For example, in [48] Biginelli-like cyclocondensations based on three-component treatment of 3-amino-l,2,4-triazole or 5-aminotetrazole with aldehydes and fluorinated 1,3-dicarbonyl compounds were investigated. It was shown that the reaction can directly lead to dihydroazolopyrimidines 20, but in the most cases intermediate tetrahydroderivatives 19 were obtained (Scheme 10). To carry out dehydration reaction, refluxing of tetrahydroderivatives 19 in toluene in the presence of p-TSA with removal of the liberated water by azeotropic distillation was used. The same situation was observed for the linear reaction proceeding via the formation of unsaturated esters 21. 

The type of products formed in reactions of /(-hydroxy acids with sulfur tetrafluoride depends on the substituents on the carbon alom adjacent to the hydroxy group. Acids such as 3-hy-droxypropanoic acid (21) and 3-hydroxybutanoic acid (22) give, in addition to 1,1,1,3-tetra-fluoroalkanes, mainly dimeric products, i.e. fluorinated esters or ethers, together with small amounts of unsaturated acid fluorides. In contrast, n7C -4,4,4-trifluoro-3-hydroxybutanoic acid (23), depending on the reaction conditions, affords 3,3,3-trifluoro-l-(lrifluoromethyl)propyl fluorosulfite or a mixture of 1,1,1.2,4,4,4-hcptafluorobutanc and l,l,1.4.4,4-hcxafluorobut-2-ene.116... 

Fluoroxytrifluoromethane, a source of electrophilic fluorine, has recently been employed by Barton et ah for the fluorination of unsaturated steroids.143,144 It is more reactive than perchloryl fluoride and therefore not without danger. It forms, for instance, a highly explosive product with pyridine.143 Like perchloryl fluoride it reacts with enol ethers, esters and enamines, but at lower temperature (— 78°) to yield the fluorinated ketones as well as addition... 

Acrylic acid esterified with cross-linked hydroxymethyl polystyrene or Wang resin reacts smoothly with primary or secondary aliphatic amines at room temperature (Entries 1 and 2, Table 10.6). Only sterically demanding amines or amines of low nucleophilicity (anilines, a-amino acid esters) fail to add to polystyrene-bound acrylate. Support-bound acrylamides are less reactive than acrylic esters, and generally require heating to undergo addition with amines (Entries 4 and 5, Table 10.6). a, 3-Unsaturated esters with substituents in the 3-position (e.g. crotonates, Entry 3, Table 10.6) react significantly more slowly with nucleophiles than do acrylates. The examples in Table 10.6 also show that polystyrene-bound esters are rather stable towards aminolysis, and provide for robust attachment even in the presence of high concentrations of amines. Entry 10 in Table 10.6 is an example of the alkylation of a resin-bound amine with an electron-poor alkene to yield a fluorinated peptide mimetic. 

Titanium(IV) isopropoxide, 311 a,(3-Epoxy aldehydes and ketones Fluorine-Acetonitrile, 135 Oxodiperoxymolybdenum-(pyridine)(hexamethylphosphoric triamide), 227 a,(3-Epoxy silanes Allyltriisopropylsilane, 11 m-Chloroperbenzoic acid, 76 Esters (see also Dicarbonyl compounds, Unsaturated esters)... 

Placing a carbonyl function next to an allylic CF2 group leads to the usual shielding, but its impact appears to be dampened by the influence of the double bond. The fluorines of a terminal allylic CF2H group to an a,/ -unsaturated ester appear to be slightly shielded (Scheme 4.65). 

Following their investigations on nitrene, carbene, and oxo transfer reactions catalyzed by fluorinated silver tris(pyrazoyl)borate (see Chapter 6 on nitrene chemistry), Lovely et al. looked for a combined carbene transfer and [2,3]-sigmatropic rearrangement. On the basis of these mechanistic considerations, these authors showed that diazoacetates, indeed, reacted with allyl halides in the presence of this silver catalyst to give a-halo-y-unsaturated esters (Scheme 3.51).77... 

In El the molecular ion is only weakly observed in the case of linear saturated hydrocarbons. The presence of branching usually entails the disappearance of this peak. However, an unsaturation, and especially an aromatic ring, makes the molecular ion peak more intense. The presence of electronegative saturated heteroatoms (oxygen, fluorine) normally prevents the observation of the molecular ion. In fact, its intensity depends on the groups that are present. Thus an aliphatic ester yields a weak or absent molecular ion, whereas an aromatic one usually yields an intense molecular ion peak. 

Other examples of the addition of fluorine to a,)S-unsaturated esters are known. 

Cationic polymerization of epoxides by irradiation of charge-transfer complexes has been mentioned in the literature Fluorinated alkanesulfonic acid salts chromates and dichromates of alkali metals, alkaline earth metals and ammonium phototropic o-nitrobenzyl esters iodocyclohexene unsaturated nitrosamines and carbamates have been reported to act as cationic photoinitiators. 

There are many examples of Ihe simultaneous addition of fluorine and bromine to a,/ -unsaturated esters.174,1 75-1 99,2 u 241-246-2 52,298... 

Acid chlorides230 256 react with alcohols to form fluorinated esters. Acid bromides257 - 259 are less regularly used. If a base is necessary, triethylamine252 255 or pyridine240-250 [with 4-(dimethylamino)pyridine251] are commonly utilized to trap the acid. Addition of a stabilizer is advantageous for the synthesis of a,/i-unsaturated esters, e.g. 10 from 9.234-255... 

Cyclizations of hydroxy esters under basic conditions have been achieved.475 Aldol reactions of a-kclo esters with aldehydes give unsaturated lactones.476 477 The photocatalytic addition of alcohols 17 to a,/ f-unsaturated acids (e. g., I8)478 or esters479 is an example of a radical process that gives fluorinated lactones (e.g.. 19). Cycloadditions to alkenes480 or alkynes481 are also successful. 

In the Horner-Wadsworth-Emmons (HWE) reaction, a lithium, sodium or potassium salt of a P-keto-phosphoric acid dialkyl ester or an a-(alcoxycarbonyl) phosphoric acid dialkyl ester is reacted with an aldehyde to form an a,p-unsaturated ketone or an a,p-unsaturated ester as product and a phosphoric acid dialkyl ester as byproduct. The product of a Horner-Wadsworth-Emmons reaction possesses a new -configured C=C double bond. To obtain products with Z-confi-guration of the C=C double bond the Still-Gennari variant or the Ando variant can be employed. The Still-Gennari variant uses two partly fluorinated F3C-CH2-O groups at the phosphorus and the Ando variant uses two aryloxy residues and the transferable alcoxycarbonyl group at the phosphorus. 

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