Fluorinated 1,3-dicarbonyls

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. 

Fluorinated 1,3-dicarbonyl reagents or their equivalents can be used as building blocks for the preparation of trifluoromethyl-substituted pyrazoles in a strategy similar to that used for the synthesis of ring-fluorinated pyrazoles. Trifluoroacetyl dihydrofuran and pyran (135 or 136), as well as trifluoro-4-ethoxy-3-butene-2-one... 

Fluorinated dicarbonyl triphenylphosphoranes, easy to prepare (by trifluoro-acetylation of the stabilised ylides), have been transformed stereoselectively into / -substituted jS-trifluoromethyl alkenoates by treatment with organolithium reagents (Eq. 115) [306]. The stereoselectivity could be reversed by O-methyla-tion of the initial adduct followed by protonation [307]. 

Fluorine Containing a-Dicarbonyl Compounds and Their Densatives (Russ ) Saloutm V L, Pashkevich, K 1, Postovskii,[ Y Usp Khun 51 1287 1304 97... 

This reaction is an example of fluorination of the methylene-group of /i-dicarbonyl compounds [15]. 

While fluoroxy compounds react well with enol derivatives, fluorine in general does not. However, there are various reports where such reactions are described and in certain cases even with decent yields. In 1982 it was reported that pyruvates with a dominant enolic form react well with fluorine, to give the corresponding fluoro derivatives l.78 Several silyl enol ethers 2 and 379 including ones made from 1,3-dicarbonyl derivatives 480 react quite satisfactorily with fluorine to give the expected a-fluoro ketones. Steroidal 16-enol acetates react with fluorine to form mainly 16a-fluoro-17-oxo steroids e.g. 5.81... 

Tetracarbonyl(trifluoromethyl)iron(II) iodide reacts with C-C bond formation to give per-fluoroethene. Tetracarbonyl(perfluorohexyl)iron(II) iodide gives several products, but no per-fluorohexene resulting from /1-elimination has been found.148 However, reductive defluorination of perfluoro(methylcyclohexane) has been reported with dicarbonyl(ty5-cyclopcn-tadienyl)iron(III).212 The defluorination is accompanied by substitution of fluorine with the cyclopentadienyl anion and proton abstraction from the solvent, the latter is well known in the chemistry of fluoroaromatics with the cyclopentadienyl anion. 

Fluorine-Containing a-Dicarbonyl Compounds and Their Derivatives ... 

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)... 

Both experimental and theoretical studies have been reported of fluoro-denitration and fluoro-dechlorination reactions using anhydrous tetrabutylammonium fluoride in DMSO. The absences of ion pairing and strong solvation are critical in contributing to the reactivity of the fluorinating agent24 Quaternary ammonium salts derived from cinchona alkaloids have been shown to be effective catalysts in an improved asymmetric substitution reaction of /1-dicarbonyl compounds with activated fluoroarenes. The products may be functionalized to yield spiro-oxindoles.25... 

The structural and stereochemical aspects of the enantioselective halogenation of 1,3-dicarbonyl compounds catalysed by Ti(TADDOLato) complexes have been report- ed.158 The observed absolute configuration at the fluorinated stereogenic centre has... 

DFIT has been employed with pyridine 9HF for monofluorinations of /3-ketoesters [104]. Similar a-fluorinations can be effected by electrolysis of Et3N 5HF solutions, containinglil mixtures of p-iodotoluene and jS-dicarbonyl compounds, in an undivided cell at 0°C. In this procedure, DFIT is generated in situ and mediates fluorination of the substrate (Scheme 34) [97]. 

Acetyl hypofluorite reacts smoothly with 1,3-dicarbonyl compounds or their enolates264. Even lithium enolates of monocarbonyl derivatives265 or methylene phosphonates, analogous to the AZT drug266, can be fluorinated directly, eliminating the need to prepare the... 

A synthesis of a set of 2-pyridylpyrroles has been described, involving annulation of 1,3-dicarbonyl compounds with 2-(aminomethyl)pyridine under acidic conditions, as illustrated by the construction of compound 437 (Equation 121) <20020L435>. Likewise, pyrroles have also been obtained from reactions between 1,3-diaryl-l,3-dicarbonyl compounds and imines or oximes promoted by the TiCU/Zn-system <2004SL2239>. Yet another approach involves rhodium-catalyzed reactions of isonitriles with 1,3-dicarbonyl synthons, which enables for instance preparation of fluorinated pyrroles <20010L421>. 

Fluorination of 1,3-dicarbonyl compounds.1 1,3-Dicarbonyl compounds that exist... 

To summarize, it can be stated that the freer the ambident anion in every respect, the larger the 0/C-alkylation ratio in the case of 1,3-dicarbonyl compounds [365]. Thus, if 0-alkylation products are desired in the alkylation of enolates, dipolar non-HBD and dissociating solvents such as A, A -dimethylformamide, dimethyl sulfoxide, or, especially, hexamethylphosphoric triamide should be used. If C-alkylation is desired, protic solvents like water, fluorinated alcohols, or, in the case of phenols, the parent phenol will be the best choice [365]. 

Initial attempts at the direct fluorination of carbonyl compounds such as acetone, bulan-2-one, and butyric acid with elemental fluorine resulted in the formation of complex mixtures, with only low yields of a-monofluorinated carbonyl compounds formed. However, more recently, methyl 3-phenylpyruvate. and other pyruvate derivatives, e.g. 1," are reported to be selectively monofluorinated with dilute elemental fluorine at — lO C in moderate yield. The success of this reaction is attributed to the fact that the substrate predominantly exists in the enol form and not the keto form." Direct fluorination of acyclic 1,3-dicarbonyl compounds in formic acid or acetonitrile at room temperatures results in the formation of 2-fluoro-... 

Dicarbonyl compounds are selectively fluorinated a to the two carbonyl groups with 1-fluoro-... 

The gaseous carbonyl difiuoridc (bp — 83 C) is used as a fluorinating agent for aldehydes and ketones. In a first reaction step, isolable fluoroformatcs are formed which are converted into the ew-difluorides 1 by loss of carbon dioxide. a-Dicarbonyl compounds yield cyclic 1,2-di-fluoroethene carbonates. ... 

In accordance with this scheme, internal fluoroalkenes are oxidized by potassium permanganate, under strictly controlled conditions, with preservation of the C-C bond to give aliphatic or alicyclic fluorine-containing a-dicarbonyl and a-hydroxycarbonyl compounds. 

The changing perspective on the viability of fluorine as a reagent is illustrated by the fact that many selective fluorinations of substrates [8] containing carbon centres of high electron density have now been described, including a variety of enolate derivatives [71, 72], stabilised carbanions [73, 74], steroids [75] and 1,3-dicarbonyl derivatives [76] (Table 3.2) as well as some aromatic compounds [77]. Fluorinated aminoacids have been obtained by direct fluorination [78] (Figure 3.10). 

Xenon difluoride has also been used for the fluorination of enol derivatives [5] and 1,3-dicarbonyl compounds [140], and fluorination of activated aromatic substrates is possible in the presence of a Lewis acid [141]. 

The importance of fluorinated organic componnds both in medicinal chemistry and biochemistry has resulted in much recent attention towards efficient carbon fluorine bond formation [30]. The reactions developed include a very successful electrophilic asymmetric mono-fluormation of 1,3-dicarbonyl compounds [31]. A nucleophilic variant was also investigated. In this context, the groups of Togni and Mezzetti have established that ruthenium Lewis acids could efficiently catalyze fluorination reactions [32]. In the presence of [Ru(l,2-bis(diphenylphosphino)ethane)2Cl][PF6] (8) (10 mol%), fert-butyl iodide reacted at room temperature with TIF (1.1 equiv.) to yield fert-butyl fluoride (84% yield). This reaction was extended successfully to a range of organic halides (Entries 1-3, Scheme 10.19). The use of the chiral complex [Ru((lS,2S)-N,N bis[2-diphenylphos-phino)benzylidene]diaminocydohexane))Cl][PF6] (9) showed modest chiral induction at the outset of the reaction (Entry 4, Scheme 10.17). The near-racemic mixture obtained at completion points to an SNl-type process in this nucleophilic halide... 

Recently, Yoneda s group has also demonstrated that the iodobenzene difluoride mediator is also effective for a-fluorination of )6-dicarbonyl compounds using Et3N SHF as the supporting salts [96]. 

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