Malonates, allylation

Geranyl acetoacetate (685) is converted into geranylacetone (686). On the other hand, a mixture of E- and Z-isomers of 688 is obtained from neryl acetoacetate (687). The decarboxylation and allylation of the allyl malonate or cyanoacetate 689 affords the o-allylated acetate or nitriie[447]. The trifluoromethyl ketone 691 is prepared from cinnamyl 4.4,4-trifluoroacetoace-tate (690)[448],... 

The allyl cyanoacetate 731 can be converted into an a, /3-unsaturated nitrile by the decarboxylation-elimination reaction[460], but allyl malonates cannot be converted into unsaturated esters, the protonation and allylation products being formed instead. 

The reaction can be applied to allyl malonates. Alkylation of diallyl mal-onate (734) with bromoacetate and acetoxymethylation afford the mixed triester 735. Treatment of the tricster 735 with Pd catalyst affords allyl ethyl itaconate (736). In a similar way, a-methylene lactone and the lactam 737 can be prepared[462]. 

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]. 

Another metal-catalyzed microwave-assisted transformation performed on a polymer support involves the asymmetric allylic malonate alkylation reaction shown in Scheme 12.4. The rapid molybdenum(0)-catalyzed process involving thermostable chiral ligands proceeded with 99% ee on a solid support. When TentaGel was used as as support, however, the yields after cleavage were low (8-34%) compared with the corresponding solution phase microwave-assisted process (monomode cavity) which generally proceeded in high yields (>85%) [30],... 

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. 

Allylic malonate 100 completely isomerizes to the thermodynamically favored linear isomer 101 on treatment with a palladium catalyst [119]. Formation of a stabilized carbanion and Jt-(allyl)palladium species facilitates the C-C bond cleavage. Analogous isomerization is also catalyzed by a nickel complex [120]. These results demonstrate that the transition metal-catalyzed nucleophilic substitution of an allylic substrate with a carbon nucleophile is reversible, if the cleaved nucleophile is sufficiently stabilized. 

Intramolecular cyclopropanation was observed to give 3-oxabicyclo[3.1,0]hexan-2-ones 2 when allyl malonates 1 were oxidized with stoichiometric quantities of manganese(III) acetate and copper(II) acetate in glacial acetic acid. ... 

Intramolecular Cyclopropanation of Allyl Malonates Under Oxidative Conditions General Procedure - ... 

More complex products are obtained from cyclizations in which the oxidizable functionality and the alkene are present in the same molecule. y9-Keto esters have been used extensively for Mn(III)-based oxidative cyclizations and react with Mn(OAc)3 at room temperature or slightly above [4, 10, 11, 15], They may be cyclic or acyclic and may be a-unsubstituted or may contain an a-alkyl or chloro substituent. Cycloalkanones are formed if the unsaturated chain is attached to the ketone. y-Lactones are formed from allylic acetoacetates [10, 11]. Less acidic /3-keto amides have recently been used for the formation of lactams or cycloalkanones [37]. Malonic esters have also been widely used and form radicals at 60-80 °C. Cycloalkanes are formed if an unsaturated chain is attached to the a-position. y-Lactones are formed from allylic malonates [10, 11]. yff-Diketones have been used with some success for cyclizations to both alkenes and aromatic rings [10, 11]. Other acidic carbonyl compounds such as fi-keto acids, /3-keto sulfoxides, j8-keto sulfones, and P-nitro ketones have seen limited use [10, 11]. We have recently found that oxidative cyclizations of unsaturated ketones can be carried out in high yield in acetic acid at 80 °C if the ketone selectively enolizes to one side and the product cannot enolize... 

Similar desymmetrization occurs via symmetric intermediate in cyclic allylic compounds. Synthesis of enantiomerically pure jasmonoids has been reported by Helmchen based on this method. The symmetric intermediate complex 102 is generated from 3-chlorocyclopentene. The allylated malonate 103 was obtained with high % ee using the phosphinyloxazoline ligand 105 and converted to the important intermediate 104 with 99% ee [40]. 

Allyl y3-keto carboxylates 563 undergo facile Pd-catalyzed decarboxylation to form either jr-allylpalladium enolates 565 or a-palladaketone 564. Also rr-allyl-palladium enolates are generated from enol carbonates 566. As summarized below, several transformations to afford 567-573 are possible under different but proper conditions depending on the substituents R [199]. In addition to allyl j6-keto carboxylates, other allyl esters such as allyl malonates, cyanoacetates and nitroacetates undergo similar transformations. With these Pd-catalyzed reactions, a new generation of j6-keto esters and malonate chemistry has been developed. 

Hydrolysis of the dialkylated jS-keto esters and malonates is not easy, and usually harsh conditions are required. Also decarboxylation occurs only at high temperature. On the other hand, hydrolysis and decarboxylation reactions of substituted allyl -keto esters and allyl malonates using Et3N-HC02H proceed at room temperature under neutral conditions. THP-protected allyl jS-keto ester 597 was converted to 598 at room temperature without deprotection of THP [213]. The free mono-carboxylic acid 600 was obtained smoothly from the disubstituted diallyl malonate 599 [214]. 

The [3,3]-sigmatropic rearrangement of allylic alcohols after condensation with ethyl 3,3-diethoxyacrylate leads to regiospecific syntheses of substituted allyl malonates in good yields (Scheme... 

Direct functionalization of cryptophane in positions other than the upper rim of the CTV fragments is very rare. One example is the direct iodination or bromination of one arene ring of cryptophane-1.1.1 using l2/PhI(OAc)2 or V-bromosuccinamide, respectively (Scheme 9). The monohalogenated cryptophanes have been used to generate deuterium, carboxylic acid, or allyl malonate derivatives. 

Interestingly, allylation of stabilized carbon nucleophiles has been found to be reversible. Complete transfer or rearrangement of dimethyl methyhnalonate moiety lirom the secondary carbon to the primary carbon, involving C—C bond cleavage, was observed by treatment of the allylated malonate with a Pd catalyst in 24 h, showing that the C—C bond cleavage of the monoallyhc system proceeds slowly (Scheme 16). 

In analogy with typical allylic electrophiles, such as halides, ethers, and acetates, allylmalonate esters undergo oxidative addition to zero-valent transition metal species to cleave the allyl-malonate bond. The oxidative addition is likely to involve the coordination of the allylic double bond as well as one of the carbonyl groups to the metal and to proceed via a cyclic transition state (Scheme 5.46). 

Oxidation of allylic -keto amides with MnjOAcjs in EtOH affords y-lactams. The primary radical formed in the cyclization abstracts a hydrogen from the solvent (eq 10). Similarly, saturated y-lactones can be prepared by oxidation of allylic malonates and acetoacetates. ... 

Another enantioselective route to 116, that features catalytic asymmetric induction, is shown here (see Prostaglandins-12 for another example). This synthesis begins with racemic allylic acetate 123. A palladium-mediated ally-lation of dimethyl malonate in the presence of chiral ligands (for the Pd) provided 124 with excellent enantioselectivity. This material was converted to 116. Alkylation as per the Mori synthesis (Juvabione-16) gave 117, which was converted to 125 using another Pd-mediated malonate allylation. Malonate 125 was converted to 126 via an intermediate tetraol. The synthesis of juvabione (15) was then completed using a short reaction sequence. 

The first example of an allylic alkylation catalyzed by iron compounds was reported in 1979. Allylic halides and carboxylates are treated with a diethyl malonate anion in the presence of sodium tricarbonyl(nitrosyl)ferrate to give the allylated malonates with good regioselectivity in favor of the ipso product (Scheme 4-195). This transformation can be carried out in a carbon monoxide atmosphere catalyzed by the Hieber-type complex [Bu4N][Fe(CO)3NO] (TBAFe) that is easier to handle. The... 

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