Problems dicarbonyls

Analysis You have two 1,5- and one 1,3-dicarbonyl relationships to consider. Discoimections like a hardly simplify the problem at all, whereas discoimecting the 1,3-dicarbonyl relationship b gives a symmetrical intermediate ... 

This is now a familiar 1,5-dicarbonyl problem the extra COiEt group tells us where to disconnect. 

Synthesis and Properties. A number of monomers have been used to prepare PQs and PPQs, including aromatic bis((9-diamines) and tetramines, aromatic bis(a-dicarbonyl) monomers (bisglyoxals), bis(phenyl-a-diketones) and a-ketones, bis(phenyl-a-diketones) containing amide, imide, and ester groups between the a-diketones. Significant problems encountered are that the tetraamines are carcinogenic, difficult to purify, and have poor stabihty, and the bisglyoxals require an arduous synthesis. 

It becomes clear that in all these compounds it is the conjugate base that takes part in the substitution proper. For mono- and particularly 1,3-dicarbonyl compounds this result actually removes the problem of whether it is the keto or the enol form which enters into an electrophilic substitution by diazonium ions, halogenating agents, and many other reagents. The keto and the enol form are distinct species, but they have one (common) conjugate base This was made clear quite early, but even today there are many chemists who seem not to be aware of it. 

The cis stereochemistry of (7) is irrelevant to (10 or (11), as cyclisation can give only ais fusion of two five-membered rings, but it might be a problem for (9). In any case, no disconnection, other than removing single carbon atoms, can easily be made on (9). Much the same is true of (12), but reconnection of the 1,6-dicarbonyl in (13) provides a good starting material (14). 

The most direct route to the 1,4-dicarbonyl equivalent required for the aldol condensation would be to couple the enol ether of an aldehyde with the enol ether of a ketone. However, this sequence proved impractical due to the hydrolytic instability of the ketone enol ether. Even after an extensive effort, the substrate for the electrolysis reaction could not be reproducibly prepared in high yield. These problems were readily avoided with the use of an allylsilane based... 

As shown, the disconnection of the consonant 1,3-dicarbonyl system present in 1 would lead to the precursor 2, the acylation of which would present problems of regioselectivity. However, disconnection of the alkyl group at the a-position of the carbonyl groups leads to precursor 3, the alkylation of which would not present any problem of regioselectivity. 

Figure 17-1 presents atypical retrosynthetic analysis problem. (The presence of a p-diccirbonyl compound indicates that the formation of a carbanion through the loss of a hydrogen ion from the a-carbon will probably be important however, don t let this distract you from the task at hand.) The problem asks you to prepare a ketone. Your first question should be, How can 1 prepare a ketone One answer to this question is to deccirboxylate a 5-dicarbonyl compound. For the compound in this problem, the reaction shown in Figure 17-2 works. 

Problem 20.5 Pyrroles, furans, and thiophenes are made by heating 1,4-dicarbonyl compounds with (NH4)2C0, P4O, and PjS, respectively. Which dicarbonyl compound is used to prepare (o) 3,4-dimethyl-furan. (h) 2,5-dimethylthiophene. (c) 2,3-dimethylpyrrole <... 

Problem 22.12 Osazones are converted by PhCHO to 1,2-dicarbonyl compounds called osones. Use this reaction to change glucose to fructose. 

The present method of preparation is that described by Bruggink and McKillop.4 It has the particular advantages of high yield and manipulative simplicity, and avoids the problem inherent in Hurt-ley s procedure of separation of mixtures of carboxylic acids by fractional crystallization or column chromatography. The method is, moreover, of wide applicability with respect to both the /3-dicarbonyl compound and the 2-bromobenzoic acid. The synthetic scope and limitations of this procedure for the direct arylation of... 

AH- Thiopyrans are directly accessible only in relatively poor yield, and then only by condensation of a suitable 1,5-dicarbonyl compound with sulfide (690PP21). As has been described earlier, this particular reaction is bedevilled with the problem of disproportionation to tetrahydrothiopyrans and thiopyrylium compounds. Thiopyran-4-ones may be prepared in a related manner by addition of sulfur dichloride to divinyl ketones, followed by base treatment (76MI22500). 

In the last chapter we used two specific enol equivalents for alkylation reactions lithium enolates and 1,3-dicarbonyl compounds. Both will help us to solve the regioselectivity problem in the... 

Thus both unsaturated carbonyl compounds 27 and 30 disconnect to the same 1,6-dicarbonyl compound 28 that reconnects to natural limonene 29. There are two chemo-selectivity problems... 

To overcome the problems associated with the inherently low yield amino acid degradation products, a-dicarbonyls have been used in place of amino acids and sugars, respectively (5-10). 

Oxidative cyclization of unsaturated /3-dicarbonyl compounds with two a-hydro-gen atoms will give products that still have one a-hydrogen and can be oxidized further. If the product is oxidized at a rate competitive with that of the starting material, mixtures of products will be obtained. For instance, oxidative cyclization of 26 affords 36 % of 27 and 10 % of dienone 28 formed by further oxidation of 27, as shown in Scheme 6 [7]. The product is occasionally oxidized much more readily than the starting material so that none of the initial product is isolated. These reactions may still be synthetically useful if the products of further oxidation are monomeric. For example, oxidative cyclization of methyl 3-oxo-6-heptenoate provides 78% of methyl salicylate [29]. The overall reaction consumes 4equiv. Mn(OAc)3. Competitive oxidation of the product is not usually a problem in inter-molecular addition reactions, because a vast excess of the oxidizable substrate, for example acetone or acetic acid, is usually used as solvent. Use of excess substrate is not possible in oxidative cyclizations. 

Our retrosynthetic analysis of the Paal-Knorr synthesis leads to a problem when applied to furan, as it implies addition of a water molecule, followed by elimination of two water molecules. In practice, simple dehydration of a 1,4-dicarbonyl compound leads to furans as in the preparation of 2.21. 

Let us consider the synthesis of flavone 9.19, which is the parent of a large series of natural products. Disconnection of the carbon-oxygen bond in the usual way results in enol 9.20 which exists as 1,3-diketone 9.21. This 1,3-dicarbonyl relationship can be exploited in the classical manner yielding orf/m-hydroxyacetophenone 9.22. The synthetic problem centres on methodology for the C-benzoylation of the enolate derived from 9.22 with some activated benzoic acid derivative 9.23. 

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