0-diketones enolization

The oxidation of (+)-epi-inosose by Acetobacter [only the (+)-form is affected] would be expected to give a meta-diketone (see p. 144), and, in fact, oxidized solutions of ( )-epi-inosose are acidic, as would be expected (since 1,3-diketones enolize readily).36... 

The conformational situation for twisted 2,2-diacyl compounds of type 29 is quite different from that for sodium or lithium 1,3-diketone enolates. In the latter, the ZZ form is stabilized by complexation with the cation75, and only in the presence of crown ethers is the EZ form observed76. The barrier to EZ - ZE exchange in the free carbanion is 12.9 kcal mol-1, as expected quite close to that found for 29. 

The reaction of an olefin with a 1,3-diketone enol, known as the de Mayo reaction [116], is an important member of the [23-2] photocycloaddition reaction family. This and related processes were discussed by Sato et al. [117]. 1,3-Dioxi-nones (62) react with ethylene to give cyclobutane products. (Kaneko et al. [118] and Demuth et al. [119] have written reviews on this subject.) The intermolecular reactions of olefins with enones, carried out by Organ et al. [120], are complementary to the work on spirodioxinone derivatives (e.g., 63) by Sato et al. [121]. Reaction of enone 64 with cyclohexene led to a mixture of seven products, with the all-cis isomer formed in 32% yield. However, higher selectivity was seen for the reaction with a protected cyclohexenone (65), which afforded the all-cis isomer (66) in 54% yield, and reaction with cyclopentene (67), which gave 68 as a single product in 90% yield, as shown in Scheme 17 (also see Fig. 8). 

Scheme 78 The reaction of a 1,3-diketone enolate with carbon disulfide leading to a 2-methylthio-3-acyl thiophene [126]...

Let s see how this can translate to the laboratory. The reaction of ethyl ace-toacetate (83) with ethyl crotonate (84) provides 85 in 55% yield. ° This sequence involves initial formation of the enolate of 83. Enolate formation is insured by the use of an activating group that is removed in a later operation. Enolate formation is followed by a conjugate addition to 84. A subsequent proton transfer and (ester enolate to ketone enolate) is followed by a nucleophilic acyl substitution whose driving force is presumably formation of a stable 1,3-diketone enolate. Protonation, ester hydrolysis and decarboxylation complete the synthesis of 86. This synthesis is a variation of 7S + 79 -> 77 76 (Functional Groups-11). 

Another approach to the spiro[4-5] decane skeleton is illustrated by the exceptionally simple stereospecific synthesis of /3-vetivone based on a novel spiroannelation reaction of cyclic 1,3-diketone enol ethers developed at Columbia. ... 

It is also generally true that the greater the number of contributing resonance forms, the greater will be the resonance stabilization. For this reason die enolate of a yS -diketone has much more resonance stabilization than die enolate of a simple ketone (three resonance forms versus two). The electrons are delocalized over five atoms in the former versus three atoms in the latter. In addition, the electron density on the carbon atom is less in the diketone enolate than in a simple methyl ketone enolate. 

The latter compounds 88 are unstable and readily hydrolyzed to isocou-marin 89 and deoxybenzoin 90 by analogy with /3-diketonic enol ethers (cf. Section III,F,2,d). The only example of electrophilic substitution in an aromatic ring conjugated with the cationic ring was described for the nitration regioselectively yielding the meta isomer 91 (84MI1). 

According to Yerma et al. [35] the mechanism of the reaction may be rationalized as involving (3-oxygenation of the bismuth(III) nitrate activated chalcone enolate, which may then undergo a Michael addition to a second a, 3-unsaturated ketone (Scheme 4.52) to form a 1,5-diketone enolate adduct 180. Subsequent heteroannulation with o-PDA via condensation and retro-aldol disproportionation may form 2-hydroxy-1,2,4,6-tetraaryl-1,2,3,4-tetrahydro-pyridine derivatives 181, which may undergo dehydration to yield 1,2,4,6-tetraaryl-1,4-dihydropyridines 177. 

Table 9. H and 2H NMR shift, A<5( H, 2H) of /8-Diketone Enol Tautomers Hydrogen Bonds...

The particular case of lithium acetylacetonate (acac), a canonic example of /I-diketone enolate, was also examined early. It was shown that its chelated (Z,Z) conformation was almost exclusive in methanol at — 60 °C and that dimers were probably formed in which one of the two lithium cations would be chelated by the two acac anions272. A somewhat similar dimer, obtained from the lithium enolate of ethyl acetoacetate complexed by a 2.1.1 cryptate, was characterized in one of the first 7Li NMR studies of enolates (Scheme 65)273. Note that the structure of the three ft -diketone mono- and dilithium enolates displayed in Scheme 64 has been studied, despite their poor solubility, in both THF-dg and DMSO-d6 by 13C NMR260. The data obtained for the monoenolates are consistent with rapidly equilibrating dimers, while the dimers of dienolates seem to form slowly on the NMR time scale. 

Pentanedione is in equilibrium with two enolate ions after treatment with base. Enolate A is stable and unreactive, while enolate B can undergo internal aldol condensation to form a cyclobutenone product. But, because the aldol reaction is reversible and the cyclobutenone product is highly strained, there is little of this product present when equilibrium is reached. At equilibrium, only the stable, diketone enolate ion A is present. 

FIGURE 5-1 Some common m/ramolecular H bonds. This page o-chlorophenol ethyl acetoacetatc (enol form) /3-diketones (enol form) salicylaldehyde. Facing page 5,8-dihydroxy-a-napthoquinone chloral hydrate oc-acetylamino acetamide. 

Among the 0-H O intramolecular hydrogen bonds, those of (S-diketone enols are resonance assisted and characterized by a low barrier in the proton transfer pathway between two equivalent tautomeric forms, through the H-centred (C2v) conformation representing the transition state (Fig. 4). 

The reaction of p-diketone enolates with vinyliodonium salts led to the a-vinyl-p-diketone derivatives in good yields, but the number of known examples is rather limited. 

The seminal paper which led to the revival of alkynyliodonium chemistry was published by Ochiai et al in 1986. The reaction of p-diketone enolates with alkynyliodonium tetrafluoroborates containing an alkyl chain led to the formation of cyclopentene derivatives such as (81). 1 ... 

Among a series of trifluoromethyl dibenzoheterocyclic onium salts derived from chalcogens, a small number of tellurium compounds have been prepared. As electrophilic trifluoromethylating agents, the tellurium compounds appeared as the least reactive. With a very reactive carbanion, the unsubstituted dibenzotellurophenium salt (81) gave only 9% of the trifluoromethylated product. With the p-diketone enolate, (81) did not react. However, the 3,7-dinitrotellurophenium salt (82) showed a relative activity similar to that of the unsubstituted selenium compound (47). 1... 

For acylations with reactive esters, such as formate or oxalate (see Section 3.6.4.5), sodium alkoxides are still the bases of choice, but sodium hydride, dimsyl sodium, sodium or potassium amide or sodium metal have all been used for the in situ generation of the enolate anion. A typical example is shown in Scheme 47. Acylation by esters results in the production of 1 equiv. of the alkoxide ion, along with the p-dicarbonyl compound proton transfer then results in the production of the conjugate base of the dicarbonyl compound. This process normally leads to the more stable anion in the acylation of an unsymme-trical ketone. The acyl group thus becomes attached to the less-substituted a-position of the ketone. The less stable 0-acylated products are normally not observed in such reversible base-catalyzed reactions. Methyl alkyl ketones are normally acylated on the methyl group where both a-carbons are substituted to the same extent, acylation occurs at the less-hindered site. Acylation is observed only rarely at a methine carbon as the more stable p-diketone enolate cannot be formed. 

Thermolysis of the photoadducts of alkoxyolefins and cyclic jS-diketone enol acetates or /3-chloroenones leads to cyclobutene derivatives capable of undergoing conrotatory ring opening. The method provides ready access to dienes which are... 

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