Acyclic 1,3-diketones

Reaction of 2-aminobenzophenone with acetyl acetone in the presence of Bi(OTf)3 (5 mol%) results in the formation of 3-acetyl-2-methyl-4-phenylquinoline [117]. Various 1,3-diketones, acyclic ketones and cyclic ketone undergo the condensation with 2-aminoaryl ketones. The scope and generality of this process is illustrated with respect to various 2-aminoaryl ketones and a wide array of a-methylene ketones, and the results are summarized in Table 6. This method is free from side reactions such as the self-condensation of ketones, which is normally observed under basic conditions. Unlike reported methods, the present protocol does not require high temperature or drastic conditions to produce quinoline derivatives. 

Better results were obtained for the reduction of acyclic diketones acyclic 1,2-diketones are excellent substrates for baker s yeast. The selectivity, however, is often rather low [121,179, 204-207]. An effective way to improve stereoselectivity of the reduction process was the introduction of a sterically demanding sulfur-containing group [208,209]. 

Shaw and McDowellhave prepared imidazolone derivatives by cyclization of a-acylamino amides. In a variation of this reaction the azlactone (30) was gradually converted to the hydroxamic acid (31) by methanolic hydroxylamine. Sodium methoxide and hydroxylamine readily gave the acyclic hydroxamic acid (32) which could be cyclized to 31 by dilute acid. Benzyloxyurea has been used in the sjrnthesis of pyrimidine hydroxamic acids (33) by reaction with /S-diketones followed by catalytic hydrogenation of the benzyl group. Protection... 

NHC-promoted enolate formation from an enal, followed by a desymmetrising aldol event to generate P-lactones and loss of CO, has been exploited by Scheidt and co-workers to generate functionalised cyclopentenes 240 in high ee from enal substrates 238 (Scheme 12.52) [94]. Interestingly, the use of alkyl ketones in this reaction manifold allows the isolation of the p-lactone intermediates with acyclic diketones, P-lactones 239 are formed with the R group anti- to the tertiary alkox-ide, while with cyclic diketones the P-lactone products have the R group with a syn relationship to the alkoxide [95]. 

Organo copper and lithium enolates of cyclic ketones, lactones, and lactams or acyclic ketones are converted with acylimidazoles or imidazole-N-carboxylates into the corresponding / -diketones or / -ketoesters ... 

The alcohol 172 obtained by reaction of 86 with ethynyl magnesium bromide on oxidation with manganese dioxide gave the ketone 17361 Glaser coupling of the ketone 173 gave an equimolar mixture of the two acyclic diketones 170 and 174. 

The enone system itself is usually part of a five- or six membered ring, although acyclic a,(3-unsaturated ketones and enols of P-diketones are also found to undergo cycloadditions under certain conditions. For seven- and higher membered rings the primary photochemical event is Z—E isomerization around the C—C double bond, the E-isomer then eventually undergoing further thermal reactions. 

The scope of Michael additions with catalysts containing cyclohexane-diamine scaffolds was broadened by Li and co-workers [95]. When screening for a catalyst for the addition of phenylthiol to a,p-nnsatnrated imides, the anthors fonnd that thiourea catalyst 170 provided optimal enantioselectivities when compared to Cinchon alkaloids derivatives (Scheme 41). Electrophile scope inclnded both cyclic and acyclic substrates. Li attributed the enantioselectivity to activation of the diketone electrophiles via hydrogen-bonding to the thiourea, with simultaneous deprotonation of the thiol by the tertiary amine moiety of the diamine (170a and 170b). Based on the observed selectivity, the anthors hypothesized that the snbstrate-catalyst... 

The Knoevenagel reaction consists in the condensation of aldehydes or ketones with active methylene compounds usually performed in the presence of a weakly basic amine (Scheme 29) [116], It is well-known that aldehydes are much more reactive than ketones, and active methylene substrates employed are essentially those bearing two electron-withdrawing groups. Among them, 1,3-dicarbonyl derivatives are particularly common substrates, and substances such as malonates, acetoacetates, acyclic and cyclic 1,3-diketones, Meldrum s acid, barbituric acids, quinines, or 4-hydroxycoumarins are frequently involved. If Z and Z groups are different, the Knoevenagel adduct can be obtained as a mixture of isomers, but the reaction is thermodynamically controlled and the major product is usually the more stable one. 

In the majority of dehydration reactions, heterocyclic compounds are formed, rather than carbocyclic compounds. Many possibilities for formation of carbocyclic compounds exist, but these are important only if (a) the heterocyclic or acyclic tautomers cannot undergo further elimination reactions, or (b) the conditions of reaction greatly favor the formation of an acyclic tautomer capable of affording only the carbocyclic compound. Both five- and six-membered carbocyclic compounds have been isolated, with reductic acid being the compound most frequently reported. Ring closure occurs by an inter-molecular, aldol reaction that involves the carbonyl group and an enolic structure. Many examples of these aldol reactions that lead to formation of carbocyclic rings have been studied.47 As both elimination and addition of a proton are involved, the reaction occurs in both acidic and basic solutions. As examples of the facility of this reaction, pyruvic acid condenses spontaneously to a dibasic acid at room temperature in dilute solution, and such 8-diketones as 29 readily cyclize to form cyclohexenones, presumably by way of 30, either in acid or base. 

Bishop and Hamer found that acyclic a,/8-unsaturated 1,2-diketones form cyclopentanol derivatives in high yield, while / ,y-unsaturated derivatives form oxetanes by internal cycloaddition.114 Unexpectedly, the y,S-unsatu-rated derivatives also gave oxetanes after an initial migration of the double bond to the /8,y position. The formation of oxetanes such as 38 was observed in the camphorquinone sensitized dimerization of butadiene.115 Photocycloadditions of a-diketones to various olefins have been studied by several groups.116... 

The atom X, still in an sp hybridization state of a heterocyclic system, is at one end of one unsaturated Y=X bond in a nonaromatic ring. The same conformational profile as in case 1 is expected if reference is made to vinyl ketones or a-diketones, which are corresponding acyclic derivatives. 

Interestingly, suppression of enolization of a particular carbonyl of a diketone chain is witnessed during the cyclization of 8-trimethylsilyl-2,6-octanedione [149]. Thus, enolization of the internal ketone toward C-7 is discouraged by the acceptor silicon, the competing influences of the two functions tend to diminish the donor properties of C-7. It should be noted that enolization toward C-5 leads to a nonproductive eno-late, as cyclization would result in a cyclobutanol, and a fast reversal to the acyclic tautomer is expected. 

Several syntheses of 2//-pyrans are based on the preparation of the acyclic precursors (157b) in the hope that the dienone zZ 2//-pyran equilibrium will favor the heterocycle (157a). Often the product will contain both valence isomers. Such dienone precursors can be obtained by Knoevenagel condensation of 1,3-dicarbonyl compounds with a,(3-unsaturated aldehydes (Scheme 57). Simple 1,3-diketones yield the 2//-pyran directly (88IZV1815) and cyclohexan-l,3-diones afford fused pyrans (82S683, 84JHC913, 87JOC1972>. 

When 2-(3-phenylprop-2-ynyl)cyclohexane-l,3-dione is heated with zinc carbonate, ring closure to a fused 4//-pyran occurs (62AP645). If the triple bond is terminal, cyclization leads to a furan derivative. Under the same conditions, the analogous acyclic diketones do not yield pyrans. 

The Claisen-type condensation reaction of cyclic vinylogous carboxylic acid triflates with lithium enolates and their analogues has provided acyclic alkynes bearing a 1,3-diketone-type moiety.19 The reaction mechanism has been proposed to proceed via a 1,2-addition of the enolate to the vinylogous acyl triflate, followed by fragmentation of the aldolate intermediate (Scheme 2). 

Desymmetrization via proline-catalyzed asymmetric intramolecular aldol reaction can, however, also be performed with acydic diketones of type 109 as has been reported by the Agami group [106], In the first step a prochiral acyclic diketone reacts in the presence of L-proline as catalyst (22-112 mol%) with formation of the aldol adduct 111 (Scheme 6.49). In this step reaction products with two stereogenic centers, 110, are formed. These chiral hydroxyketones 110 are subsequently converted, via dehydration, into the enones 111, by treatment with p-toluenesulfonic acid. 

The most general method for the formation of selenopyrylium salts from acyclic precursors involves the reaction of 1,5-diketones with a dibasic source of selenium, mainly hydrogen selenide, or by reaction of the 5-chloropenta-2,4-... 

Iodine, NIS, PhSeCl, and AUCI3 have been shown to trigger the electrophilic 6(O) "-endo-dig cyclization of 2-(alk-l-ynyl)alk-2-en-l-ones (22) to produce highly substituted furans (23) (Scheme 3). Various nucleophiles, including functionally substituted alcohols, H2O, carboxylic acids, 1,3-diketones, and electron-rich arenes, and a range of cyclic and acyclic 2-(alk-l-ynyl)alk-2-en-l-ones readily participate in these cyclizations.40... 

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