Rearrangements ester-ketene silyl acetal

On the other hand, methylaluminum bis(4-bromo-2,6-di-fert-butylphenoxide) can effect the a-alkylation of enol silyl ethers of a variety of ketones, esters and some aldehydes108. Use of the (Z-Bu)Me2Si group is recommended in the ketene silyl acetal substrates. Use of a less bulky Me3Si or Et3Si group leads to a mixture of monoalkylation products and rearranged a-silyl esters. 

The sequential Michael addition/Ireland-Claisen reactions proceed with high diastereoselectivity in one pot. Preparation of the lithium enolate 68 with LDA in THF at —78 °C followed by the addition of the allylic ester acceptor 67 leads to the smooth conjugate addition, whose stereoselectivity was more than 98% diastereomeric excess. The ketene silyl acetal 70, which was formed by the trapping of the Michael addition intermediate 69 with TMSCl, underwent Ireland-Claisen rearrangement in the presence of PdCl2(PhCN)2... 

Whereas the lithium enolates of acetate and propionate esters of difluoroallylic alcohols are known to fragment rapidly, methoxy- and benzyloxy-acetates have been found151 to form chelated enolates which undergo a smooth [3,3]-sigmatropic rearrangement as their silyl ketene acetals to afford highly functionalized difluoro compounds (see Scheme 33). Allenic silyl ketene acetals (117) have been used152 to prepare 2-substituted methyl 3,4-dienoates (118). 

Marshall, J. A. Stereochemical control in the ester enolate Claisen rearrangement. Stereoselectivity in silyl ketene acetal formation. Chemtracts Org. Chem. 1991,4,154-157. 

The cyclopropanols 13 were separated from the ketone by column chromatography and rearranged to eucarvone. In a closely related process, the addition of chloro(methyl)carbene to ketene alkyl silyl acetals afforded adducts 14 which were transformed without isolation into esters of 2-methyl-substituted a,/i-unsaturated acids 15. ... 

The earliest examples of Ireland-Claisen rearrangements of allyl silyl ketene acetals bearing a stereocenter at C6 were reported by Cha and Lewis in 1984 (Scheme 4.36) [40]. In contrast to the nitrogen C6 substituents, oxygen substituents exhibited considerably less facial bias. Rearrangements of the acetate esters of either the Eor Z alkenes gave only 1.3 1 and 1.4 1 C3,C6 anti.syn ratios, respectively. 

The reaction of lithium diisopropylamide with propargyl acetate 3.559 followed by treatment of the enolate formed with trimethylchlorosilane at —78°C affords ketene acetal 3.561. After heating the reaction mixture to 40°C, the intermediate vinylpropargyl ether 3.560 undergoes the Claisen rearrangement to produce silyl ester 3.561, which after hydrolysis forms allenyl-acetic acid 3.562 with a 50% overall yield (Scheme 3.42) [281]. This reaction is of interest as a synthetic strategy for obtaining the benzoannelated enyne-allene that by radical cyclization forms polycyclic aromatic compounds with an embedded fluorene section [281]. (Scheme 3.43)... 

Schemes 28 and 29 illustrate Curran s synthesis of ( )-hirsutene [( )-1]. Luche reduction58 of 2-methylcyclopentenone (137), followed by acetylation of the resulting allylic alcohol, furnishes allylic acetate 138. Although only one allylic acetate stereoisomer is illustrated in Scheme 28, compound 138 is, of course, produced in racemic form. By way of the powerful Ireland ester enolate Clai-sen rearrangement,59 compound 138 can be transformed to y,S-unsaturated tm-butyldimethylsilyl ester 140 via the silyl ketene acetal intermediate 139. In 140, the silyl ester function and the methyl-substituted ring double bond occupy neighboring regions of space, a circumstance that favors a phenylselenolactonization reac-...

The silyl ketene acetal rearrangement can also be carried out by reaction of the ester with a silyl triflate and tertiary amine, without formation of the ester enolate. Optimum results are obtained with bulky silyl triflates and amines, e.g., f-butyldimethylsilyl triflate and (V-methyl-Af, /V-dicyclohcxylaminc. Under these conditions the reaction is stereoselective for the Z-silyl ketene acetal and the stereochemistry of the allylic double bond determines the syn or anti configuration of the product.243... 

The stereoselectivity of silyl ketene acetal Claisen rearrangements can also be controlled by specific intramolecular interactions.246 The enolates of a-alkoxy esters adopt the Z-configuration because of chelation by the alkoxy substituent. 

Scheme 6.16. Rearrangement of Silyl Ketene Acetals and Ester Enolates...

Entries 10 to 15 involve use of the Ireland-Claisen rearrangement in multistep syntheses. An interesting feature of Entry 11 is the presence of an unprotected ketone. The reaction was done by adding LDA to the ester, which was premixed with TMS-C1 and Et3N. The reaction generates the T-silyl ketene acetal, which rearranges through a chair TS. 

The ester 7-1 gives alternative stereoisomers when subjected to Claisen rearrangement as the lithium enolate or as the silyl ketene acetal. Analyze the respective transition structures and develop a rationale to explain these results. 

When the lactone silyl ketene acetal 18-1 is heated to 135° C a mixture of four stereoisomers is obtained. Although the maj or one is the expected [3,3] -sigmatropic rearrangement product, lesser amounts of other possible C(4a) and C(5) epimers are also formed. When the reaction mixture is heated to 100° C, partial conversion to the same mixture of stereoisomers is observed, but most of the product at this temperature is an acyclic triene ester. Suggest a structure for the triene ester and show how it can be formed. Discuss the significance of the observation of the triene ester for the lack of complete stereospecificity in the rearrangement. 

Claisen-type rearrangements of ester enolates, ketene acetals, and silyl ketene acetals... 

Allylic esters of fluoroacetic acid were used in the Ireland silyl ketene acetal rearrangement procedures by the Welch group at Albany [164]. For example, Eq. (53) shows a highly diastereoselective rearrangement which formed an early stage in syntheses of 2,3-dideoxy-2-fluoro-3-C-methyl pentose nucleosides [165, 166]. If a stereoselective synthesis of a functionalised monofluorocompound is... 

Vinyl sulfoxides (221), which are aldehyde a-cation equivalents, and vinylthiolium ions (230), which are a.jj-unsaturated carbonyl 3-cation equivalents, are also suitable acceptors for silyl ketene acetals and enol silyl ethers (Scheme 36). Kita reports that the bulky r-butyldimethylsilyl ketene acetals and tri-methylsilyl ketene acetals form 1 1 adducts (224) and 1 2 adducts (225) with (221), respectively 91 mechanistically, these additions proceed via an initial Pummerer rearrangement The vinylthiolium ion additions are notable for their synthetic flexibility for example, additions to the ketene dithioacetal (229) proceed with higher diastereoselectivity than the corresponding enolate additions to a,3-unsaturated esters.9 lc,91d... 

This gentle variant of the Claisen Rearrangement employs the allyl ester of a carboxylic acid instead of an allyl vinyl ether. The ester is converted to its silyl-stabilized enolate (silyl ketene acetal), which rearranges at temperatures below 100 °C. 

---