Ketones triketones

The cyclization of 1,3,5-triketones to pyrones will not be discussed here, although this is a related reaction, because pyrones are not true pyrylium salts. Mention will be made, however, of the formation of 2,6-diphenyl-4-pyrone from 1,3-dibenzoylallene this ketone adds secondary amines leading to 3-dialkylamino-l,5-diphenyl-4-penten-l,5-diones, which arc cyclized by hydrogen chloride in acetic acid to 2,6-diphenyl-4-dialkylaminopyrylium chlorides (R = Me and/or Ph) (see Scheme. 5). 

The [ 2 + 4]-cycloaddition reaction of aldehydes and ketones with 1,3-dienes is a well-established synthetic procedure for the preparation of dihydropyrans which are attractive substrates for the synthesis of carbohydrates and other natural products [2]. Carbonyl compounds are usually of limited reactivity in cycloaddition reactions with dienes, because only electron-deficient carbonyl groups, as in glyoxy-lates, chloral, ketomalonate, 1,2,3-triketones, and related compounds, react with dienes which have electron-donating groups. The use of Lewis acids as catalysts for cycloaddition reactions of carbonyl compounds has, however, led to a new era for this class of reactions in synthetic organic chemistry. In particular, the application of chiral Lewis acid catalysts has provided new opportunities for enantioselec-tive cycloadditions of carbonyl compounds. 

In this example, the /3-diketone 2-methyJ-l,3-cyclopentanedione is used to generate the enolate ion required for Michael reaction and an aryl-substituted a,/3-unsaturated ketone is used as the acceptor. Base-catalyzed Michael reaction between the two partners yields an intermediate triketone, which then cyclizes in an intramolecular aldol condensation to give a Robinson annulation product. Several further transformations are required to complete the synthesis of estrone. 

As in 10-104, a ketone attacks with its second most acidic position if 2 mol of base are used. Thus, P-diketones have been converted to l,3,5-triketones. ° ... 

In a related reaction, heating ketones in the presence of TlClsOTf leads to 1,3,5-trisubstituted arenes. " Nitriles react with 2 mol of acetylene, in the presence of a cobalt catalyst, to give 2-substituted pyridines. " Triketones fix nitrogen gas in the presence of TiCU and lithium metal to form bicyclic pyrrole derivatives. " ... 

Crocq et al. (1997) have synthesized trimegestone through Bakers yeast mediated reduction of a ketone (this material is a new progestomimetic molecule for the treatment of postmenopausal diseases). The key step of the multistep synthesis is the chemo-, regio- and almost stereospecific bioreduction of a triketone to the desired alcohol. 

Reaction of phenyl vinyl ketone with cyclopentanone under thermal conditions resulted in a diastereomeric mixture of 1,5,9-triketones 374 via a double Michael reaction. Treatment of this mixture with ammonium formate in polyethyleneglycol-200 under microwave irradiation conditions led to the very fast and efficient formation of a 2 1 diastereomeric mixture of cyclopental flquinolizidines 375 and 376 <2002T2189>. When this reductive amination-cyclization procedure was carried out starting from the purified /ra r-isomer of 374, the result was identical to that obtained from the cis-trans mixture, showing the operation of thermodynamic control (Scheme 86). 

Conjugate addition of RN02 to enones. Primary nitroalkanes and a, (3-enones when activated by alumina form conjugate addition products that are oxidized in situ by alkaline hydrogen peroxide to 1,4-diketones. A similar reaction of nitromethane with a vinyl ketone provides 1,4,7-triketones. 

An analogous reaction is known with aromatic nitroso-compounds, but for it an exceptionally mobile hydrogen atom must be present in the ketone and hence no condensation occurs with simple ketones such Us acetone. The products of the reaction are, of course, azomethines. This condensation has made possible the synthesis of 1 2 3-triketones (F. Sachs), e.g. 

The autoxidation of cyclic ketones with dirhenium decacarbonyl under basic catalytic conditions produces dicarboxylic acids (68-73%) bicyclic ketones are converted into keto carboxylic acids and, when one ring is aromatic, quinones are obtained, e.g. 1-tetralone produces 2-hydroxy-1,4-naphthaquinone (93%), and H02C(CH2)4C0(CH2)3C02H (85%) is obtained from 1-decalone via a cyclic triketone [5]. 

In order to activate the 21 position to halogenation, it is hrst converted to an oxalate. Condensation of the triketone with ethyl oxalate in the presence of alkoxide proceeds preferentially at the 21 position to give (12-2) due to the well-known enhanced reactivity of methyl ketones. Reaction of the crude sodium enolate with bromine leads to the dibromide (12-3), the oxalate moiety being cleaved under the reaction conditions. The Favorskii rearrangement is then used to, in effect, oxidize the 17 position so as to provide a site for the future hydroxyl group. Thus, treatment of (12-3) with an excess of sodium methoxide hrst provides an anion at the 17 position (12-4). This then cyclizes to the transient cyclopropanone (12-5)... 

Treatment of the mercurio ketone with Ni(CO)4 results in a symmetrical coupling with incorporation of one molecule of carbon monoxide to give a triketone presumably via a 3-nickel substituted ketone Eq. (28) [34], This symmetrical coupling reaction is general for alkyl mercury compounds. 

In the presence of base, alcohols and phenols add l,5-diphenylpenta-l,4-diyn-3-one (72JOU1398). At 40 °C addition occurs at both triple bonds to give a mixture of the 1,5-dialkoxy compound (411), the triketone and the pyran-4-one. On treatment with acid the former compounds are converted into the pyranone. However, at 15 °C only one triple bond is attacked giving the alkoxyvinyl ethynyl ketone (412), but this also forms the pyranone with acid (Scheme 136). 

On treatment with acetic anhydride in pyridine, the yellow tetraketone (68), the yellow triketone (66), and the diketone (67) afforded monoacetyl, diacetyl, and triacetyl derivatives, respectively. All these derivatives contained a tertiary acetoxyl group. However, comparisons of 1H-NMR spectra of the parent ketones with those of the acetyl derivatives indicated that a rearrangement of the molecule or a major conformational change must have occurred. On the basis of extensive H-NMR spectral analysis, structure 69 was proposed for the diacetyl derivative which was derived from the triketone 66. Structure 69 was justified on the basis of conformational arguments. 

Reaction of phosphorus pentasulfide with j3,8-triketones leads to l fiayS -trithiapentalenes.1,2-8> 52 This was the first synthesis of trithiapentalenes known, but its development was delayed until practical methods for preparing 3,8-triketones were available. One of these procedures is the acylation of ketones in the presence of sodium hydride.53 Another method begins with the diacylation of the enamine derived from a cyclanone.38... 

The triketone shown here is called ninhydrin and is used for the detection of amino acids. It exists in aqueous solution as a monohydratc. Which of the three ketones is hydrated and why ... 

Base catalysis is not required for conjugate addition. If the nucleophile is sufficiently enolized under the reaction conditions then the enol form is perfectly able to attack the unsaturated carbonyl compound. Enols are neutral and thus soft nucleophiles favouring conjugate attack, and p-dicarbonyl compounds are enolized to a significant extent (Chapter 21). Under acidic conditions there can be absolutely no base present but conjugate addition proceeds very efficiently. In this way methyl vinyl ketone (butenone) reacts with the cyclic P-diketone promoted by acetic acid to form a quaternary centre. The yield is excellent and the triketone product is an important intermediate in steroid synthesis as you will see later in this chapter. 

Compartmental ligands (16) are derived from diketonates and triketonates and are usually synthesized from Schiff base reactions of the ketone with a diamine. ... 

The conjugate addition of dithiols to hexa-l,4-diyn-3-ones yields p,P -bis-l,3-dithiane ketones, masked 1,3,5-triketones, which have been converted into dihydro- and tetrahydro-pyrans <03OLl 147>. 

Compounds having methylene groups situated between two activating groups—ketone, acid, or ester—are readily oxidized with selenium dioxide to furnish triketones, keto diesters, a,/3-diketo esters,or a-keto acids. ... 

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