Methylene bis-dicarbonyl compounds

Interestingly, they were able to perform this transformation sequentially starting from a large excess of N,N-dimethylaniline (10 equiv.) and the ketoester 10-A under standard conditions this reaction was stopped at the formation of the oxidative coupling adduct 10-B which could be obtained in 47% yield (together with 37% of 10-C). The reaction of 1 equiv. of 10-B with one extra equivalent of 10-A led to the methylene bis-dicarbonyl compound 10-C in 91% yield, indicating that 10-B can be an intermediate of the reaction (Scheme 4.10). 

Scheme 4.10 Proposed pathway to obtaining methylene bis-dicarbonyl compounds.

The competition between Michael addition of a,(3-unsaturated ketones and Diels-Alder reactions involving furan and 2-methylfuran is affected by the catalyst used. Methyl vinyl ketone gives the alkylation product with furan and 2-methylfuran in the presence of silica gel (88TL175). Bis(alkylated) products have also been obtained in reactions of 2-methylene-1,3-dicarbonyl compounds (90H(31)1699). An intramolecular proton catalyzed alkylation reaction of an a,(3-unsaturated ketone provided a straightforward synthesis of norpinguisone (90TL4343) and in the example shown in Equation (4) the cyclization reaction involved an a,(3-y,8-dienone (94TL4887). 

Dicarbonyl compounds, such as malonate derivatives, can also be classified under two categories. As well as reacting simply as a three-atom bis-electrophilic fragment (as in the synthesis of barbiturate 10.25 (page 77), an alternative reactivity is available. Condensation (by nucleophilic attack) of the active methylene carbon and electrophilic reaction at just one of the carbonyl groups is a two-atom nucleophilic/electrophilic profile, as seen in the preparation of coumarin 9.16. 

In a related reaction, condensation of 1,3-dicarbonyl compounds (323) with methylene bis-imidazolidine (324) gave substituted imidazo[l,2-a]pyridines (325) (78LA1491). The reactions of aldehydes (326) with ethyl 2-imidazolidinyleneacetate (327), or those of aldehydes (326) and jS-dicarbonyl compounds with imidazolidines (330) gave similar structures (328) and (331) (78LA1476, 73GEP2210633). 

In a very similar manner, tandem 1,6- and 1,4-additions of -dicarbonyl compounds to methyl 2,4-pentadienoate were utilized by Danishefsky and coworkers- foi the formation of several bi- and tricyclic ring systems. For example, reaction of the enolate of dimedone with this ester gave the expected 1,6-addition product protonation/deprotonation set the stage for a subsequent intramolecular 1,4-addition (equation 9). Likewise, a ketodiester was used to transform the pentadienoate in a one-pot procedure by consecutive 1,6- and 1,4-additions into a richly functionalized tricyclic product which was then converted into the natural product ( )-cpiclovane (equation 10). According to this principle, Irie and coworkers obtained several decalin-2,7-diones by treatment of 2-methylen-2-cyclohexenones with dimethyl 3-oxoglutarate. 

A similar dramatic influence of ionic liquid was also reported by Ranu s group in the Michael reaction of active methylene compounds with methyl vinyl ketone and methyl acrylate in the presence of an ionic liquid, 1-butyl-3-methylimidazolium hydroxide ([bmImjOH). Interestingly, open-chain 1,3-dicarbonyl compounds reacted with methyl vinyl ketone and chalcone to give the usual monoaddition products, whereas the same reactions with methyl acrylate or acrylonitrile provided exclusively bis-addition products (Scheme 5.55). 

Iron-catalyzed oxidation of iV-methyl amines in the presence of tert-butylhydroperoxide (TBHP) affords methylene-bridged bis-l,3-dicaii)onyl compounds (Scheme 4-256). The reaction possibly proceeds following a two-step or three-step mechanism. In both cases, an oxidative (dehydrogenative) coupling of the amine methyl group with the methylene carbon atom of the 1,3-dicarbonyl compound takes place first Second will be either an amine elimination/addition sequence or direct Sn2 displacement of the methylaniline by the carbon nucleophile. ... 

The Knoevenagel condensation with 1,3-dicarbonyls followed by a Michael reaction of a second molecule of the methylene compound, with or without addition of an amine or ammonia, may be used for the qualitative and quantitative determination of aldehydes even in the presence of ketones. Thus, cyclic 3-diketones such as dimedone (59) react with aldehydes but not with ketones in the absence of a catalyst. For the characterization the bis(2,6-dioxo-4,4-dimethylcyclohexyl)methanes (67) or the 4,6-dioxo-2,2,8,8-tetramethyl-1,2,3,4,5,6,7,8-octahydro-SW-xanthene (68) may be used.93,104,105... 

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