1.3.5- Triketones, reaction with

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. 

If a precursor contains more than two carbonyl groups, the reaction with H2S involves those in 1,5-positions. Thus in the case of triketones 53, products 20 (R = H, Me) were isolated in yields of 96 and 94%, respectively.61,99 4//-Thiopyran 20a (R = H) isomerizes under the reaction conditions.100... 

Aromatic esters may be used to aroylate the dianions derived from 1,3-diketones by reaction with potassium amide (60JOC538). Not only are acetyl and benzoyl acetones suitable for reaction, but alicyclic diketones and 2-hydroxyacetophenone are also acceptable. Cycliz-ation of the triketones occurs in cold sulfuric acid, presumably via the enolic form and the hemiacetal (Scheme 132). 

Pyridyne has proved elusive, but the brief existence of a derivative has been demonstrated through its reaction with furans.63 Favorskii intermediates and similar three-carbon transients64 have been found to add readily to furans in several studies an example used for synthetic purposes by Matzinger and Eugster produced the tricyclic triketone shown in Scheme 12.65 Very similar reactions occur with the transients formed by treating... 

Although these microbial reactions may substitute for chemical resolution methods, they likewise have the inherent disadvantage that only one half of the material is theoretically utilizable, for the substrate is already chiral. It is therefore preferable to design substrates with pro-chiral centers suitable for microbial asymmetric inductions. Examples that have been applied in the prostaglandin area follow. Reduction of triketone 40 with Dipodascus uninucleatus and Mucor rommanianus furnished the (R) and (S) alcohols (41 and 42) respectively. 6 The (R) alcohol (41) was then chemically converted into 43, a key synthon for prostaglandin synthesis via conjugate addition. 

For the acylation of anisole by acetic anhydride over HBFA and HY, the reasons for the deactivation accord with those already reported for the reaction with veratrole. Unfortunately, di- or triketones were not extractible and, also, deactivation of the... 

Reactions with Phenanthraquinone, 9-Arylxanthenes, and Diphenyl Triketone. J. Chem. Soc. 997 (1947). 

Reaction of that triketone with ethylene glycol selectively forms the expected 3,20-bisacetal the still free remaining ketone at Cn is next reduced with lithium aluminum hydride to yield the expected /8-hydroxyl group (11-1) (Scheme 7.11). Acid hydrolysis of the acetal groups followed by reaction with selenium dioxide generates the... 

The six-membered ring must therefore be disconnected first. The a,18-disconnection gives triketone (43) with all 1,4-reIationships, and the best strategy here is to use an acyl anion equivalent for the central carbonyl group and disconnect by two Michael reactions. 

Developed in the early 1970s, this reaction, also called the Hajos-Parrish reaction or Hajos-Parrish-Ender-Sauer-Wiechert reaction, is one of the earliest processes for the stereoselective synthesis of Wieland-Miescher ketone, an important building block for steroids and terpenoid synthesis. This reaction is a proline mediated asymmetric variation to the Robinson annulation. Hajos and Parrish of Hoffmann-La Roche Inc. in 1971 and 1974 published an asymmetric aldol cyclization of triketones such as that of structure 39, which affords optically active annulation products in the presence of catalytic amounts of (S)-proline (Z-proline). One of the early examples is the synthesis of 41 from the triketone 39 (a product of the Michael addition of MVK to the corresponding 2-methylcyclopentane-l,3-dione), the reaction is performed in two steps first by ring formation in the presence of 3 mol % of (iS)-proline in DMF to afford the ketol 40 in 100% yield after crystallization with 93% ee and then by reaction with toluenesulfonic acid to give the dehydrated adduct 41. The formation of the Wieland-Miescher Ketone 44 follows the same synthetic route, starting from the tri-ketone 42 to give the end product in 75% optical purity and 99.8% of optical yield. 

Synthesis via ABD fragments with five- or six-membered D rings has also been effected by using the Michael reaction with trienones (Scheme 40). The trienone (416) necessary for this purpose was obtained from the methoxytetralone (8) via the dihydro derivative (412) and the carbinol (413) with an over-all yield of 65% [526-530]. Its condensation with 2-methylcyclohexane-l,3-dione under the action of Triton B gave the triketone (415), which readily cyclized to the diketol (418). The trans-anti configuration of the latter was established on the basis of a conformational... 

Condensation of the vinyl ketone (554) with 2-methyl-1,3-eyelopentane-dione led to the bicyclic triketone (565) with a five-membered ring D (Scheme 54) [463, 509, 616-618]. The reaction was carried out in boiling methanol containing traces of caustic potash a weakly alkaline medium was selected in order to keep to a minimum the expected tendency of the triketone (565) to undergo a reverse Michael reaction [439]. The cycliza-tion of (565) under the action of p-toluenesulfonic acid enabled the estra-pentaenone (395) to be obtained [463,509] the conversion of this into the methyl ether of estrone (133) and its 8-iso analog has been described in detail in Scheme 39. The over-all yield of (133) on the bromide (547) by this method was 18%. ... 

Schonberg, A. and Mustafa, A., Photochemical reactions in sunlight. Part Xll. Reactions with phenanthraquinone, 9-arylxanthene, and diphenyl triketone, J. Chem Soc., 997,1947. 

The final two stages are very straightforward. Oxidative scission of the C3-C5 double bond in 6 with ozone provides triketone 5 which, without purification, is subjected to a base-induced intramolecular aldol/dehydration reaction. The crystalline product obtained from this two-step sequence (45 % overall yield) was actually an 85 15 mixture of ( )-progesterone and a diastereomeric substance, epimeric at C-17. Two recrystallizations afforded racemic progesterone [( )-(1)] in diastereomerically pure form. 

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. " ... 

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. 

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. 

Mononuclear V02+ and heterodinuclear V02+ complexes (with Cu2+, Ni2+, Mn2+, Zn2+, Pd2+ as the second metal ion) have been reviewed.894 In this section, we shall mainly discuss more recent work. Many complexes were with Schiff bases from the reaction of /3-triketones or /3-ketophenols with ethylenediamine. One important aim has been to compare the magnetic, spectral and chemical properties for the metal ion Ma in [Ma(diken)] and Mb in [Mb(diketonato)2], with the corresponding properties in the binuclear complexes formed (see equation 66). 

This type of interesting phenomenon has also been observed in non-organometallic reactions. The Hajos-Wiechert intramolecular aldol reaction of the triketone to the bicyclic aldol exhibits a nonlinear relation between the enantiomeric purity of the (S)-proline catalyst and the en-antioselectivity (Scheme 44) (75). With the partially resolved amino acid, the cyclization affords the product in an ee lower than anticipated. The reaction occurring via an enamine intermediate again may be interpreted in terms of participation of two proline molecules in the productdetermining transition state. 

Dimethyloxosulfonium methylide reacts with the triketone (212) to give the fused 2-hydroxymethylenedihydropyran (213) (76H(4)1755). The reaction is thought to proceed through a zwitterion and the epoxide as indicated in Scheme 41. Intramolecular nucleophilic attack leads to the dihydropyran and the overall process may be regarded as a transfer of methylene from the sulfur ylide. 

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