Triketones, preparation

Unsaturated hydrazones, unsaturated diazonium salts or hydrazones of 2,3,5-triketones can be used as suitable precursors for the formation of pyridazines in this type of cyclization reaction. As shown in Scheme 61, pyridazines are obtainable in a single step by thermal cyclization of the tricyanohydrazone (139), prepared from cyanoacetone phenylhydrazone and tetracyanoethylene (76CB1787). Similarly, in an attempted Fischer indole synthesis the hydrazone of the cyano compound (140) was transformed into a pyridazine (Scheme 61)... 

Ethylene ketals can be readily prepared by the ethylene glycol technique. 6-Ethylene ketals can also be prepared by exchange dioxolanation and suitable conditions have been described for the preparation of either the 3-mono-ketal (78), the 3,6-diketal (79) or 3,6,17-triketal (80) from the triketone... 

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. 

Regioisomers of pyrrolizines 255 and their dihydroanlogues 256 were obtained as a mixture, in moderate yield, by reacting the 1,4,7-triketones 254 with titanium-nitrogen complexes (ClTi=NTMS, Cl2TiN(TMS)2, and N(TMS)3) prepared by reduction of TiCU with lithium under a nitrogen atmosphere (Scheme 69) <2004BCJ1655>. 

The diacylation of isopropenyl acetate with anhydrides of dicarboxylic acids is applicable for the synthesis of several other cyclic jS-triketones in moderate yield. - It has been used for the synthesis of 2-acetylcyclohexane-l,3-dione (40% yield), 2-acetyl-4-methylcyclopentane-l,3-dione (10% yield), 2-acetyl-4,4-dimethylcyclopentane-l,3-dione (10% yield), 2-acetyl-5,5-dimethylcyclohexane-l,3-dione (10% yield), 2-acetylcyclo-heptane-l,3-dione (12% yield) and 2-acetylindane-l,3-dione (26% yield). Maleic anhydrides under more drastic conditions give acetylcyclopent-4-ene-l,3-diones in yields from 5% to 12%. The corresponding acylation of the enol acetate of 2-butanone with succinic anhydride has been used to prepare 2-methylcyclopentane-l,3-dione, an important intermediate in steroid synthesis. - ... 

Triketone (57), a key intermediate in the synthesis of 4,4,7,7,11,11-hexanitropentacyclo [6.3.0.0 .0 °.0 ]undecane (61) (Zlj-hexanitrotrishomocubane), has been synthesized independently by both Marchand and co-workers, and Fessner and Prinzach. Marchand and co-workers prepared the trioxime (58) from the corresponding triketone (57). Oxidation of (58) with peroxytrifluoroacetic acid in acetonitrile provides a direct route to the trinitro derivative (59) in 35 % yield, this yield reflecting an efficiency of 70 % for the oxidation of each oxime group. Subsequent oxidative nitration of (59) with sodium nitrite and potassium ferricyanide in aqueous sodium hydroxide yields the target T>3-hexanitrotrishomocubane (61). 

Stractures of 3-alkyl-5-methylindolizidines, found in thief ants, Solenopsis species (Table II), arrived at by gas chromatographic and mass spectral analysis were confirmed by coinjection and direct comparison with the synthetic sample. Indolizidine 15a from S. conjurata exhibits characteristic peaks at miz 152 (M — CHj) and 138 (M — C2H5, a base peak) as well as a parent peak at m/z 167 in the mass spectram. It corresponds to an isomer of 3-ethyl-5-methylindolizidine (15) which was prepared as a mixture of four stereoisomers by reductive amination of triketone 391 with ammonium acetate-sodium cyanoborohydride and sodium borohydride (Scheme 47). 

Triketones are useful intermediates in the preparation of 4-pyrones, 4-pyridones,3,4 and other cyclic products. 

A further interesting case is provided by the synthesis of ninhydrin (Expt 5.99, cognate preparation) from indane-l,3-dione (Expt 7.9) in which the methylene group is activated by two adjacent carbonyl groups. Ninhydrin is the stable monohydrate of the triketone, indane-l,2,3-trione, and is a well-known colorimetric reagent for amino acids (Section 2.31). 

Cyclopenteno-5,6-cycloalkeno-47/-pyran-4-ones 724 are prepared by the reaction of 1-cyclopentenylpiperidine with diacyl chlorides via formation and ring closure of the 1,3,5-triketone intermediate 723 (Scheme 179)... 

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... 

Carefully dried apparatus and solvent are a prerequisite of ozonation. A solution of the ylide (10 mmol) in dichloromethane (100-200 ml) was ozonized with an ozonizer (oxygen mixture) at - 40 to — 60°C, depending on the ylide. The most reactive ylides required only the equimolecular amount of ozone. When the peroxide test was negative the deep-coloured solution was concentrated and the residue purified by distillation, sublimation or recrystallization. More than 20 triketones were prepared in this way, in yields ranging between 65 and 92%. 

The venomous constituent of the cryptic thief ant, Solenopsis xenovenenum, has been identified as the 3-heptyl-5-methylpyrrolizidine (50) from its mass spectrum and the fact that a related pyrrolidine (51) has been isolated from another species of ant.47 This is the first reported occurrence of a 3,5-dialkyl-pyrrolizidine, and its structure was confirmed by synthesis. Reductive amination of the known triketone (52) with sodium cyanoborohydride and ammonium acetate gave a mixture of four isomers of 3-heptyl-5-methylpyrrolizidine, which were separated by preparative g.l.c. The stereochemistry of the ring-junction of each isomer was established from its i.r. and n.m.r. spectra. 

Through careful ozonolysis of480 in the presence of pyridine, it has proved possible to prepare triketone 481. The X-ray crystal structure analysis of 481 clearly... 

Oxidation. DMSO in combination with catalytic amounts of iodine and a strong acid oxidizes methylene groups activated by an adjacent benzoyl group in good yield. The method is only suitable for preparation of diaryl di- and triketones. Examples ... 

An asymmetric aldolization was successfully applied to the preparation of gibbane. The total synthesis of the macrolide antibiotic erythromycin was developed involving an asymmetric aldolization step catalyzed by proline. Since the mid-1970s, a flood of papers has appeared dealing with the asymmetric aldolization of various triketones. Some results are listed for comparison in Table 1. 

Efforts directed towards the synthesis of stable, perhaps isolable, cyclopropenyl anions having three identical anion stabilizing groups, such as cyano or benzoyl, have been attempted without much success. Tricyanocyclopropene (22a) could not be prepared except as a transient intermediate which could be trapped with diphenylisobenzofuran The corresponding triketone (22b) was obtainable, but attempted generation of the corresponding anion was thwarted by conjugate (Michael) addition of the base to the double bond. The cyclopropenyl anion remains an illusive species ... 

The preparative procedure for prochiral triketone 34 was simplified a solution of 34 and unnatural D-(+)-proline in dimethyl sulfoxide was degassed and then stirred at room temperature for 6 days, although Crabbe and coworkers reported a time saving variation of the preparation by using DMF as solvent.24 The reaction mixture was worked up, and the crude product obtained was purified by a vacuum distillation and by a column chromatography on silica gel to give optically active (8af )-(-)-33, [a]o -68.4° (c 1.355, benzene) as a syrup in 82% chemical and 69% optical yields. 

Therefore several reactions were subjected to various antibody catalyses, e. g., ester and enol ether cleavage, transesteiification, ketone reduction. Cope rearrangement, ring closure via epoxide opening, or Diels-Alder cycloaddition [74, 75]. An exceptional reaction is the antibody-catalyzed Robinson annulation of triketone 28 to the Wieland-Miescher ketone 29 on a preparative scale. Surprisingly, even the alkylation of diketone 27 with methyl vinyl ketone was catalyzed by the same antibody, but at moderate rates (Scheme 15) [76]. 

Many macrocyclic SBs have been prepared by condensation of different dicarbonyl precursors (head units (55), see Scheme 16) such as 2,6-diformylpyridine (56, R = H, 56a), 2,6-diacetylpyridine (56, R = CH3, 56b), 2,6-diformyl-4-Z-phenol (57, Z = C1- 57a, CH3-, 57b), 2,6-diacetyl-4-Z-phenol (57, Z = C1—, 57c, Z = CH3, 57d) thiophene-2,5-dicarbaldehyde (58), furan-2,5-dicarbalde-hyde (59), pyrrole-2,5-dicarbaldehyde (60), 2,6-diformyl-4Z-thiophenol (61, Z = CH3, 61a Z Bu1, 61b) or /3-triketones (62) with a wide range of different diamines (lateral chains). The majority of SB macrocycles are symmetrical and contain either phenol or pyridine as head units. Asymmetrical SB macrocycles have also been prepared. The SB macrocycles are designated [1 + 1] and [2 + 2] depending on the number of head and lateral units present (see Scheme 17). With certain precursors (i.e., 2,6-diacetylpyridine and l,3-diamino-2-hydroxypropane) [3 + 3] and [4 + 4] macrocyclic complexes have also been synthesized.177-179 The [2 + 3] condensation products have also... 

The asymmetric sulfide oxidation described in Scheme 2 has a (-)-NLE until eeaux=70% [5]. The (S)-proline catalyzed cyclization of a triketone shows a weak asymmetric depletion [5], as does allylic oxidation of cyclohexene in the presence of a catalyst prepared from Cu(OAc)2 and (S)-proline [41]. 

Triketone mono-dithioacetals, 5-diketones prepared from 2-acyl-1,3-dithianes (Section... 

B. Diphenyl Triketone Hydrate A solution of 34.3 g. (0.42 mole) of fused sodium acetate in 142 cc. of hot glacial acetic acid is prepared in a i-l. round-bottomed flask 72.4 g. (0.19 mole) of dibenzoyldibromomethane is added, and the mixture is refluxed until the precipitation of sodium bromide ceases (one and one-half to two hours). The mixture is then cooled to room temperature and diluted with 150-200 cc. of water with constant shaking to dissolve the inorganic salt and to precipitate the triketone hydrate, which separates as a white, curdy mass (Note 4). This is separated by filtration, washed well with water, and dried in an oven at 60°. The melting point varies from 65 to 90°, depending upon the extent of dehydration that occurs during the drying operation. The yield is 41.5 g. (86 per cent of the theoretical amount based on the dibenzoyldibromomethane). 

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