Esters allylic, reaction with malonate

The decarboxylation of allyl /3-keto carboxylates generates 7r-allylpalladium enolates. Aldol condensation and Michael addition are typical reactions for metal enolates. Actually Pd enolates undergo intramolecular aldol condensation and Michael addition. When an aldehyde group is present in the allyl fi-keto ester 738, intramolecular aldol condensation takes place yielding the cyclic aldol 739 as a main product[463]. At the same time, the diketone 740 is formed as a minor product by /3-eIimination. This is Pd-catalyzed aldol condensation under neutral conditions. The reaction proceeds even in the presence of water, showing that the Pd enolate is not decomposed with water. The spiro-aldol 742 is obtained from 741. Allyl acetates with other EWGs such as allyl malonate, cyanoacetate 743, and sulfonylacetate undergo similar aldol-type cycliza-tions[464]. 

Nucleophilic Substitution of xi-Allyl Palladium Complexes. TT-Allyl palladium species are subject to a number of useful reactions that result in allylation of nucleophiles.114 The reaction can be applied to carbon-carbon bond formation using relatively stable carbanions, such as those derived from malonate esters and (3-sulfonyl esters.115 The TT-allyl complexes are usually generated in situ by reaction of an allylic acetate with a catalytic amount of fefrafcz s-(triphenylphosphine)palladium... 

Allylic carboxylation. Diethyl oxomalonate (1) undergoes a thermal ene reaction with mono-, di-, and trisubstituted alkenes at 145 180°. The reaction is also subject to catalysis with Lewis acids, which can lead to a different ene product. The products are a-hydroxymalonic esters. The corresponding malonic acids are converted to carboxylic acids by bisdecarboxylation with NaI04 and a trace of pyridine- or with ceric ammonium nitrate (CAN). Diethyl oxomalonate then functions as an cnophilic equivalent of C02. 

Sodium hydrosulfide was found to afford a thiirane 67 upon reaction with 2-iodomethylcyclopropane-l,l-dicarboxylic acid diethyl ester <2005TL469>. In addition, 2-allyl malonic ester 68 was obtained. Scheme 12 shows the reasonable mechanisms proposed by the authors. 

Z)-2-butenylene dicarbonate with dimethyl malonate gives a low yield (20—40%) of 2-vinylcyclopropane-l,l-dicarboxylate with up to 70% ee (Scheme 2-38) [54], Reaction with methyl acetoacetate or acetylacetone takes place in a different manner to give a dihydrofuran derivative (59% ee), which results from nucleophilic attack of enolate oxygen at the cyclization step, (c) Asymmetric elimination of an acetyl-acetate ester gives (R)-4-rerr-butyl-l-vinylcyclohexene of up to 44% ee (Scheme 2-39) [55]. (d) Palladium-catalyzed allylic silylation is also applied to asymmetric synthesis... 

Cyclopropane formation was observed with other branched ester enolates but not with malonate and other enolates. Methyl and alkoxycarbonyl groups are found to be tolerable in the terminal position of the allyl ligand for reaction to occur but not a phenyl group. ... 

There is no general solvent that is useful for all reactions, and BTF naturally has its limitations. In addition to the limitations posed by the freezing point, boiling point and chemical stability mentioned before, BTF is not very Lewis-basic and therefore is not a good substitute for reactions that require solvents like ethers, DMF, DMSO, etc. Not surprisingly, ions are not readily dissolved in BTF and many types of anionic reactions do not work well in BTF. For example, attempted deprotonations of esters and ketones with LDA in BTF were not successful. Reaction of diethyl malonate with NaH (5 equiv) and reaction with Mel[72] (6 equiv) in BTF was very heterogeneous and yielded 60% of the di-methylated product, compared to 89% in THF. No reaction was observed if the same malonate anion was used as a nucleophile in a Pd-catalyzed allylic substitution reaction in BTF (see 3.7). Wittig reactions also did not work very well in BTF. The ylid of ethyl triphenyl phosphonium bromide [73] was formed only slowly in BTF, and the characteristic deep red color was never obtained. 

As shown above many allylic compounds can be used for catalytic reactions with different reactivity. Allylic esters such as carbonates, acetates, and phosphates are widely used. Allylic acetates and phosphates react in the presence of bases such as EtsN and AcONa. However, Giambastiani and Poli reported that allylation of -keto esters, but not malonates, with allylic acetates can be carried out under neutral conditions, although the reaction is slower [5]. 

Pfaltz and coworkers [56] applied the ESI-MS technique for parallel screening of Pd-catalyzed enantioselective allylation reaction of diethyl ethyl malonate with allylic esters. Enantiodiscrimination of a palladium catalyst with different chiral ligands was... 

Their reactivities are different. Although allylation with allylic chlorides proceeds without a Pd catalyst, their reaction is accelerated in the presence of a Pd catalyst. Allylic alcohols are rather poor substrates. Instead, their esters, typically allylic acetates, are used for smooth allylation. Allylic phosphates are more reactive than allylic acetates, and the chemoselective reaction of the allylic phosphate moiety of the bis-allylic compound with 1 equiv of malonate without attacking the allylic acetate moiety occurs (Scheme 5). Then the aminated product is obtained by the addition of amine. In addition to allylic esters, even allylic nitro compounds i-Piand sulfonest Hio] aHyiatjoj, Reactions of... 

Reactions of soft carbon nucleophiles derived from active methylene compounds such as /3-keto esters or malonates proceed by attack of the nucleophiles at the central sp carbon of the allenyl complexes. The attack of the nucleophiles generates cr-allyl anion intermediates, which are regarded as palladium-carbene complexes. These intermediates pick up a proton from the active methylene compound to form 7r-allylpalladium complexes, which undergo further reaction with the nucleophile as expected, and hence the alkenes are formed by introduction of two molecules of the carbon nucleophiles (Scheme 21). 

The reaction was extensively stndied for cinnamyl esters (acetate and carbonate) as allylic snbstrates, with some examples given for allyl acetate and its homologues, and a wide range of nncleophiles inclnding N-nucleophiles (primary and secondary amines, hydroxylamine and its derivatives, and sodium azide), C-nucleophiles (malonates, ethyl acetoacetate, acetylacetone, sodium tetraphenylborate), and S-nucleophile sodium p-toluenesuhinate. 

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