Fluorinated 3-Diketones

Selective fluonnation in polar solvents has proved commercially successful in the synthesis of 5 fluorouracil and its pyrimidine relatives, an extensive subject that will be discussed in another section Selective fluonnation of enolates [47], enols [48], and silyl enol ethers [49] resulted in preparation of a/phn-fluoro ketones, fieto-diketones, heta-ketoesters, and aldehydes The reactions of fluorine with these functionalities is most probably an addition to the ene followed by elimination of fluonde ion or hydrogen fluoride rather than a simple substitution In a similar vein, selective fluonnation of pyridmes to give 2-fluoropyridines was shown to proceed through pyridine difluondes [50]... 

The fluorination of P-diketones and p-ketoesters with N-/luorobis(trifluo-romethanesulfonyl)imide (Table 3a, B) can be controlled to give either mono-fluorination or difluorination. Monofluorination occurs when the strong acid, bis(trifluoromethanesulfonyl)imide, a reaction product, is removed by addition of water, which prevents further enolization and fluormation of the monofluoro adduct [83] (equation 38)... 

Fluorinated esters may also act as electrophiles in reactions with nonfluori-nated ketones [28] (equation 23) or malononitrile [29] (equation 24). Unfortunately, the yields of -diketones may be modest, but those of p-keto nitnles are excellent (Table 9)... 

Frequently, the decomposition of fluorine compounds results in a product with fewer carbon atoms through loss of carbon monoxide, carbon dioxide, or even an organic molecule Perfluonnated a-diketones undergo decarbonylanon with cesium fluoride in diglyme [90] (equation 57)... 

CHEC-II(1996) comprehensively outlines the most commonly used synthetic approaches applied to these types of bicyclic compounds of phosphorus, arsenic, antimony, and bismuth <1996CHEC-II(8)863>. The six classes of compounds listed in this section have received considerable attention over the review period and as such the principal synthetic methods for these compounds are discussed. Schoth et al. <2000CCR101> have reviewed the use of fluorinated 1,3-diketones, 2-trifluoroacetylphenols, and their derivatives in the synthesis of phosphorus compounds. Included in this review is the use of these reagents for the synthesis of various [3.3.1] nonfused and [3.3.0] fused phosphorus bridgehead bicyclic systems. 

Chambers RD, Fox MA, Sandford G (2005) Elemental fluorine - Part 18. Selective Direct Fluorination of 1,3-Ketoesters and 1,3-Diketones using Gas/ Liquid Microreactor Technology. Lab Chip 5 1132-1139 Cheng RP, Gellman SH, DeGrado WF (2001) Beta-Peptides From Structure to Function. Chem Rev 101 3219-3232... 

The efficient and selective catalysis of some Diels-Alder reactions by lanthanide P-diketonate complexes has been known since 1975 [226, 227]. The fluorinated p-diketonate complexes Ln(fod)3 (cf. Scheme 12.5) selectively catalyze the Danishefsky transformation (Scheme 12.23) as a consequence of their mild Lewis acidity. Importantly, zeolites and Lewis acid modified silica or alumina also catalyze Diels-Alder reactions [228-232]. 

Recent studies have involved some fluorinated monothio-jS-diketones with zinc and nickel (195) and palladium and platinum (196). Both nickel and zinc show valence change of the metal. 

A range of fluorinated pyrazolo[3,4- ]pyridines have been prepared by cyclization of pyrazoles with P-diketones (Equation 55 Table 31) <2004SC4359>. 

Europium(III), and particularly ytterbium(III) shift reagents, induce downfield proton resonance shifts while the praseodymium(III) analogs cause upfield shifts. Lanthanide chelates of fluorinated /3-diketonates are more soluble in organic solvents, and they form more stable association complexes with donor molecules, than do LSRs with nonfluorinated ligands. Thus Eu(fod)3 is the preferred achiral LSR for weak nucleophiles89. 

Recently, it has been shown that /1-diketones [126],/ -ketoesters (Fig. 48) [126] and N, N-dialkyl-/ -ketoamides [127] can be fluorinated directly, in high yield, at convenient temperatures (0 10 °C), in polar solvents such as formic acid or acetonitrile. As in the case of the pyruvates, the overall rate of reaction was a... 

Diketones react more rapidly with fluorine than the corresponding keto-esters, and dialkyl malonates do not react at all under these conditions. However, if dialkyl malonates are first converted into their sodium salts, reaction with fluorine gives the corresponding fluoro-compound (Fig. 50) [128]. 

Substitution of hydrogen by fluorine in compounds with acidic a-hydrogens can be achieved with xenon difluoride and some catalysts. Thus, room-temperature fluorination of 1,3-diketones, e g. 20, with xenon difluoride in the presence of the insoluble cross-linked polysty-rene-4-vinylpyridine, either complexed with boron trifluoridc or Nafion-H, as catalyst, gives mono and difluoro products.27-28... 

Many [M(dik)4] complexes are volatile, especially those that contain fluorinated diketonate ligands. Mass spectra and gas chromatographic behavior of several of these complexes have been studied (see Table 10). Isenhour and coworkers240 241 have employed fluorinated diketonates in mass spectrometric procedures for determination of Zr and Zr/Hf ratios in geological samples. The most intense peak in mass spectra of [M(dik)4] complexes is [M(dik)3]+. Sievers et al.242 have used gas chromatography of metal trifluoroacetylacetonates to separate Zr from Al, Cr and Rh. However, attempts to separate [Zr(tfacac)4] and [Hf(tfacac)4] by gas chromatography were unsuccessful. Zirconium and hafnium can be separated by solvent extraction procedures that employ fluorinated diketones.105 [M(dik)4] (M = Zr or Hf dik = acac, dpm, tfacac or hfacac) have been used as volatile source materials for chemical vapor deposition of thin films of the metal oxides.243,244... 

The mass spectra of various /3-diketonates have been extensively studied.762,763 The availability of ionization energies, measured by mass spectra, has led to a fairly detailed debate as to the nature of the orbital from which the first electron ionizes.764 Gas phase rearrangements,765 often involving fluorine migration to the metal, have been observed. The SIMS spectrum of [Cr(acac)3] is particularly simple,766 yielding the base peak [Cr(acac)2]+. 

---