Dicarbonyl compounds fluorination

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]. 

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. 

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. ... 

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]. 

Fluorination. These reagents are easy to handle and they readily find applications in fluorinating a great variety of compounds including phenols, silyl enol ethers, and 1,3-dicarbonyl compounds. 

Using the microflow system, various selective fluorination reactions can be carried out. For example, fluorination of (3-dicarbonyl compounds proceeds with high efficiency (Table 8.1). Fluorination of organosulfur compounds can also be carried out using microflow systems, as shown in Scheme 8.1. 

Oxidative addition of elemental fluorine to appropriate 1,3-dicarbonyl compounds provides a convenient synthesis of perfluorinated 1,2-dioxolanes. In this way (20) may be formed from difluoromalonyl fluoride, F2C(COF)2 <92JST(274)163>, and (39) is similarly prepared from either hexafluoroacetylacetone or the copper(II) or nickel(II) chelate of trifluoroacetylacetone with concomitant replacement of all remaining hydrogen atoms by fluorine <65JOCI429>. 

There are, perhaps surprisingly, many complex polyfluorinated starting materials available commercially and some apparently quite exotic reagents and intermediates can be easily (and often cheaply) prepared from these. These intermediates may simply be the fluorinated analogues of standard intermediates, for example, 1,3-dicarbonyl compounds or their equivalents, such as an iminium salt synthon for fluoromalonaldehyde. ... 

Dicarbonyl compounds are selectively fluorinated a to the two carbonyl groups with 1-fluoro-4.6-bis(trifluoromethyl)pyridinium 2-sulfonate (2) at room temperature. In sharp contrast, the fluorination of carbonyl compounds with l-fluoro-2,4,6-trimethylpyridinium trifluoro-methanesulfonate (3) requires heating and Lewis acid catalysis (Table 6). The reactivity of the pyridinium N-F reagent is dependent on the electronic nature of the substituents on the ring.41 When two equivalents of. V-fluoropyridinium salts were used for the fluorination of 1,3-dicarbonyl compounds, the major product was the 2,2-difluoro derivate (Table 7). 

The introduction of fluorine into /3-dicarbonyl compounds, as well as the replacement of vinylic tributylstannyl groups, have also been reported. 

Electrophilic fluorination. Fluorination of aromatic compounds is effective in 98% formic acid or sulfuric acid with a 1 9 mixture of F2-N2 at room temperature. The yield for direct fluorination of 1,3-dicarbonyl compounds by this system varies from 15% to 90%. 

Fluorination. Internal salts such as (1) are excellent fluorinating agents for styrenes 2 examples, 24-51%), anisole (83%), thioanisole (80%), 2,3-dihydrofuran (75%), silyl. -nol ethers (4 examples, 88-93%), and p-dicarbonyl compounds (5 examples, 46-98%). 

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