Dicarbonyl compounds decarboxylation

In addition to formation from a ketone, the hydra2ones can be obtained from dicarbonyl compounds by a Japp-Klingemann reaction. This is especially useful for P-ketoesters and P-ketoacids, which undergo either deacylation or decarboxylation. 

The Hantzsch pyridine synthesis involves the condensation of two equivalents of a 3-dicarbonyl compound, one equivalent of an aldehyde and one equivalent of ammonia. The immediate result from this three-component coupling, 1,4-dihydropyridine 1, is easily oxidized to fully substituted pyridine 2. Saponification and decarboxylation of the 3,5-ester substituents leads to 2,4,6-trisubstituted pyridine 3. 

In a similar way, carbocycles having a quaternary center could be obtained from acyclic unsaturated 1,3-dicarbonyl compounds [206]. Other combinations are the domino hydroformylation/Wittig olefmation/hydrogenation described by Breit and coworkers [207]. The same group also developed the useful domino hydroformyla-tion/Knoevenagel/hydrogenation/decarboxylation process (Scheme 6/2.14) [208] a typical example is the reaction of 6/2-66 in the presence of a monoester of malonic acid to give 6/2-67 in 41 % yield in a syn anti-ratio of 96 4. Compounds 6/2-68 and 6/2-69 can be assumed as intermediates. 

Strecker aldehyde are generated by rearrangement, decarboxylation and hydrolysis. Thus the Strecker degradation is the oxidative de-amination and de-carboxylation of an a-amino acid in the presence of a dicarbonyl compound. An aldehyde with one fewer carbon atoms than the original amino acid is produced. The other class of product is an a-aminoketone. These are important as they are intermediates in the formation of heterocyclic compounds such as pyrazines, oxazoles and thiazoles, which are important in flavours. 

P-relationship to the keto group. This group may thus be removed by a sequence of acid-catalysed hydrolysis, followed by thermal decarboxylation (see Section 10.9). The final product in this sequence is therefore a 8-ketoacid, i.e. a 1,5-dicarbonyl compound. 

In contrast, /3-dicarbonyl compounds such as malonic ester and acetoacetic ester are more acidic than alcohols. They are completely deprotonated by alkoxides, and the resulting enolates are easily alkylated and acylated. At the end of the synthesis, one of the carbonyl groups can be removed by decarboxylation, leaving a compound that is difficult or impossible to make by direct alkylation or acylation of a simple ester. 

Cyclization with acid now causes a lot to happen. The 1,4-dicarbonyl compound cyclizes to a lactone, not to a furan, and the redundant ester group is lost by hydrolysis and decarboxylation. Notice that the double bond moves into conjugation with the lactone carbonyl group. Finally, the reduction gives the furan. No special precautions are necessary—as soon as the ester is partly reduced, it loses water to give the furan whose aromaticity prevents further reduction even with UA1H4. H... 

Dibromo-l-(phenylsulfonyl)-l-propene (15) undergoes a similar addition/elimination reaction with anions of 1,3-dicarbonyl compounds (14) (Scheme 3). The addition/elimination product after decarboxylation (16) under-... 

A simpler and more versatile route to comparably functionalized bicyclooctanes has been developed more recently by Weiss and his co-workers.174-176 Specifically, the reaction of 1,2-dicarbonyl compounds with dimethyl 3-ketoglutarate (dimethyl acetonedicarboxylate) in aqueous solution at pH 5, or preferably in a citrate-phosphate buffer, followed by hydrolytic decarboxylation, affords 117 in good... 

Strecker [34] discovered that the reaction between amino acids (glycine, alanine, leucine) and the tricarbonyl compound alloxan yields CO2 and aldehydes. The Strecker degradation of amino acids occurs also with dicarbonyl compounds [35] including those that are formed in the course of the Maillard reaction, in particular deoxyglycosones and some of the smaller sugar fragments like 7 and diacetyl. Fig. 3.22 shows the reaction pathway that involves the formation of an imine 8, followed by decarboxylation and liberation of the resulting aminoketo compound and the Strecker aldehyde from the intermediate 10. Odour-active Strecker aldehydes which... 

Figure 17-1 presents atypical retrosynthetic analysis problem. (The presence of a P-dicarbonyl 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 decarboxylate a P-dicarbonyl compound. For the compound in this problem, the reaction shown in Figure 17-2 works. 

According to Carlin et al. (1986), the exact mechanism of oxazole formation is not known, despite the previous schemes proposed by Vitzthum and Werkhoff (1974a,b) and by Ohloff and Flament (1978). Formation pathways were proposed by Baltes and Bochmann (1987d) and Mottram (1991). For Vitzthum and Werkhoff (1974b), one pathway could be the decarboxylation of serine or threonine into ethanolamine or methylethanolamine condensation with an aldehydic compound into an oxazolidine, then oxidation into an oxazole unsubstituted or methylated on position 5 and bearing an alkyl or an acyl radical on position 2. Another pathway could be the condensation of amino acids with a-dicarbonyl compounds, followed by a Strecker degradation, formation of an a-amino ketone which, after acylation... 

Dicarbonyl compounds can be made to cyclize with esters of 3-thiapentanedioic acid 21 under base catalysis (Hinsberg synthesis). This widely applicable and high-yield synthesis leads to substituted thiophene dicarboxylic esters 22 via a double aldol condensation, with the two CH2 groups of 21. Hydrolysis and decarboxylation of the esters yield 3,4-disubstituted thiophenes 23 [23] ... 

The decomposition of these intermediates leads to the formation of ene-diols, also known as reduc-tones, in redox equilibrium with a-dicarbonylated compounds. These are responsible for the oxidation of plant tissues. The a-dicarbonylated compounds resulting from the rearrangement of the Amadori and Heyns intermediates may in turn add amino acids from must and wine (Figure 8.28). The corresponding addition products develop by intramolecular decarboxylation, according to the well-known Strecker breakdown reaction. Amino acids that become involved in this reaction ultimately become aldehydes. 

In Section 23-2 two reactions of S-dicarbonyl compounds are presented. The first is alkylation of the readily deprotonated carbon in the middle. The second pertains to (3-dicarbonvl compounds where at least one of the carbonyl groups is an ester. Ester hydrolysis leads to a carboxylic acid that readily loses CC3 (decarboxylation). When this sequence is carried out on a (3-ketoester, the result is a ketone. When carried out on a diester of propanedioic (tnakmic) acid, the result is a carboxylic acid. In each case, groups attached in the preliminary alkylation slept s) wind up in the product. 

The strategy of using decarboxylation of a p-dicarbonyl compound is described on p. 597 of the textbook. 

The Strecker degradation involves the oxidative deamination and decarboxylation of a a-amino acid in the presence of a dicarbonyl compound. The products formed from this reaction are an aldehyde containing one less carbon atom than the original amino acid and an a-aminoketone (Table 9.2). The Strecker degradation of methionine and cystein is a source of sulfur-containing intermediates (e.g hydrogen sulfide and 2-methylthiopropanal = methional) [48]. 

These doubly stabilized anions are alkylated so well that it is common to carry out an alkylation between two carbonyl groups, only to remove one of them at a later stage. This is made possible by the fact that carboxylic acids with a 3-carbonyl group decarboxylate (lose carbon dioxide) on heating. The mechanism below shows how. After alkylation of the dicarbonyl compound the unwanted ester is first hydrolysed in base. Acidification and heating lead to... 

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