Simple /3-diketonates

Mono-enol ethers of j3-dicarbonyl compounds have been used more frequently than mono-acetaJs, and they are more stable. From simple /3-diketones they can be prepared under esterification conditions [244a, 245], and frequently with isobutanol [246, 247, 248, 249, 250]. However, methyl enol ethers can also be prepared using diazomethane [251, 252]. Usually the less-hindered ketone group is converted into its enol ether [249, 250]. In /3-keto aldehydes the aldehyde can be converted by O-alkylation of the enolate salt with a bulky alkylating a nt such as isopropyl bromide [247, 253]. 

Simple diketones such as 2,3-butanedione are rapidly deprotonated by 02, but the original diketone is recovered upon acidification (equation 144). However, benzil (PhCO-COPh) cannot enolize and is dioxygenated by O2 to give two benzoate ions (equation 145). Carbon dioxide reacts rapidly with 02 in aprotic solvents with a net stoichiometry in acetonitrile (equation 146) and the proposed reaction path involves an initial nucleophilic addition (equation 147). 

Intramolecular pinacolic coupling reactions have also proven successful with Stnl2. Yields with simple diketones are relatively low. i> However, excellent yields and diastereoselectivities are achieved in intramolecular pinacolic coupling reactions of P-keto ester and P-ketoamide substrates (equation 72). A variety of substitution patterns can be tolerated in these reactions to generate five-membered carbo-cycles. Six-membered rings can also be generated by this process, but substantially lower yields and diastereoselectivities are observed (equation 73). Yields obtained for p-ketoamide substrates are also lower than those observed in the P-keto ester series. 

Simple diketones such as 2,3-butanedione are rapidly deprotonated by 02"-, but the original diketone is recovered upon acidification (Scheme 7-10). 

Enamides and enecarbamates are considered as versatile synthetic building blocks in organic synthesis, but they have been rarely used as nucleophiles, presumably due to their lower reactivity compared with enamines and enols. In 2004, Kobayashi et al demonstrated the utility of enecarbamates as nucleophiles for C-C bond formation in asymmetric copper-catalysed reactions of aldehydes and aldimines. Later in 2005, these authors reported the enantioselective nickel-catalysed reactions of a simple diketone, such... 

Reactive Immunization with the Simple Diketone Derivative... 

If we want to make a simple 1,5-diketone we may have to use an activating group like C02Et to control the reaction. How would you make TM 119 ... 

No intennolecular reaction of malonate or /3-keto esters with halides has been reported, but the intramolecular reaction of /3-diketones such as 790 and malonates proceeds smoothly[652,653]. Even the simple ketone 791 can be arylated or alkenylated intramolecularly. In this reaction, slow addition of a base is important to prevent alkyne formation from the vinyl iodide by elim-ination[654]. 

In practice this reaction is difficult to carry out with simple aldehydes and ketones because aldol condensation competes with alkylation Furthermore it is not always possi ble to limit the reaction to the introduction of a single alkyl group The most successful alkylation procedures use p diketones as starting materials Because they are relatively acidic p diketones can be converted quantitatively to their enolate ions by weak bases and do not self condense Ideally the alkyl halide should be a methyl or primary alkyl halide... 

Enolization (Sections 18 4 through 18 6) Aldehydes and ke tones having at least one a hydro gen exist in equilibrium with their enol forms The rate at which equilibrium is achieved is in creased by acidic or basic cata lysts The enol content of simple aldehydes and ketones is quite small p diketones however are extensively enolized... 

Monooximes of a-diketones have found applicability in the synthesis of 2-aminopyrazine 1-oxides by condensation with a-aminonitriles, and this reaction was used by White and coworkers in an approach to the synthesis of Cypridina etioluciferamine (Scheme 66 R = 3-indoloyl) (73T3761). In this instance, the use of TiCU as a catalyst was essential, since the carbonyl group in 3-acylindoles is normally deactivated and the required amine/carbonyl condensation is impractically slow. Under normal circumstances the carbonyl group in simple alkyl-substituted monoximes of a-diketones is the more reactive site and the reaction is rapid, requiring no catalysis (69LA(726)loo). 

Use of the trapping agent is recommended as the most efficient method for running acyloin condensations for many reasons. Among them are (a) the work-up is very simple filter and distil (b) the bis-(silyloxy)olefin is usually easier to store than the free acyloin and is readily purified by redistillation (c) unwanted base-catalyzed side reactions during reduction are completely avoided and (d) the bis-(silyloxy)olefin can be easily converted directly into the diketone by treatment with 1 mole of bromine in carbon tetrachloride.Other reactions are described in Riihlmann s review and in Organic Reactions ... 

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]... 

OL Alkylation of aldehydes and ketones (Section 18.15) Alkylation of simple aldehydes and ketones via their enolates is difficult. p-Diketones can be converted quantitatively to their enolate anions, which react efficiently with primary alkyl halides. 

Several carboxylates, both simple salts and complex anions, have been prepared often as a means of precipitating the An ion from solution or, as in the case of simple oxalates, in order to prepare the dioxides by thermal decomposition. In K4[Th(C204)4].4Fl20 the anion is known to have a 10-coordinate, bicapped square antipris-matic structure (Fig. 31.8b). -diketonates are precipitated from aqueous solutions of An and the ligand by addition of alkali, and nearly all are sublimable under vacuum. [An(acac)4], (An = Th, U, Np, Pu) are apparently dimorphic but both structures are based on an 8-coordinate, distorted square antiprism. 

A thioamide of isonicotinic acid has also shown tuberculostatic activity in the clinic. The additional substitution on the pyridine ring precludes its preparation from simple starting materials. Reaction of ethyl methyl ketone with ethyl oxalate leads to the ester-diketone, 12 (shown as its enol). Condensation of this with cyanoacetamide gives the substituted pyridone, 13, which contains both the ethyl and carboxyl groups in the desired position. The nitrile group is then excised by means of decarboxylative hydrolysis. Treatment of the pyridone (14) with phosphorus oxychloride converts that compound (after exposure to ethanol to take the acid chloride to the ester) to the chloro-pyridine, 15. The halogen is then removed by catalytic reduction (16). The ester at the 4 position is converted to the desired functionality by successive conversion to the amide (17), dehydration to the nitrile (18), and finally addition of hydrogen sulfide. There is thus obtained ethionamide (19)... 

Under different conditions (in aqueous electrolyte) the selectivity of the cleavage reaction may be perturbed by the occurrence51-53 of a dimerization process. Thus, while the major process remains the two-electron reductive pathway, 20% of a dimer (y diketone) may be isolated from the cathodic reduction of PhC0CH2S02CH3. The absence of crosscoupling products when pairs of / -ketosulphones with different reduction potentials are reduced in a mixture may indicate that the dimerization is mainly a simple radical-radical coupling53 and not a nucleophilic substitution. 

Ordinary ketones are generally much more difficult to cleave than trihalo ketones or p-diketones, because the carbanion intermediates in these cases are more stable than simple carbanions. However, nonenolizable ketones can be cleaved by treatment with a 10 3 mixture of t-BuOK—H2O in an aprotic solvent such as ether, dimethyl sulfoxide, 1,2-dimethoxyethane (glyme), and so on, or with sohd t-BuOK in the absence of a solvent. When the reaction is applied to monosubstituted diaryl ketones, that aryl group preferentially cleaves that comes off as the more stable carbanion, except that aryl groups substituted in the ortho position are more readily cleaved than otherwise because of the steric effect (relief of stain). In certain cases, cyclic ketones can be cleaved by base treatment, even if they are enolizable. " OS VI, 625. See also OS VH, 297. 

The base-stabilized germanimine (Me2Si)2(N-t-Bu)4Ge=N(SiMe3) does not react with benzophenone, even upon heating.72 Apparently, no other reactions between stable germanimines and simple carbonyl compounds have been investigated however, the reaction with a diketone, 3,5-di-r-butyl-ort/io-quinone, has. Both a [2 + 2] and a [2 + 4] cycloaddition reaction have been postulated the initially formed adducts are unstable and decompose (see Scheme 4). 

The monoketone bis(2,2, /V,/V -bipyridyl)ketone forms a [CoinL2]+ complex on reaction with [Co(NH3)4(C03)]+ in water.981 As reported for a quite different Co11 complex, the ketone is hydrated to form the gem diol which binds as a monodeprotonated O-donor along with the two pyridine groups in a tridentate chelate, with very little distortion from octahedral observed in the complex. This appears to represent a facile route for this type of inherently poor donor to achieve coordination. Chelated /3-diketonate anions are long-studied examples of O-donor chelates, and continue to be examined. A simple example is the m-[Co(acac)2(NH 3)2]1 (acac = 2,4-pentane-dionate), structurally characterized and utilized to produce molecular mechanics force field parameters for /3-diketones bound to Co111.982... 

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