Claisen rearrangement ketene acetal

Ireland-Claisen (silyl ketene acetal) rearrangement... 

Sol 1. (d) Abstraction of proton from a-methyl group of ester and subsequent treatment with trimethylsilyl chloride (TMSCl) resulted in the formation of cyclohexenyl silyl ketene acetal, which on heating undergoes [3,3] shift, i.e., Ireland—Claisen (silyl ketene acetal) rearrangement. The final step is the removal of the silyl group by acid hydrolysis to get the free acid. 

A prominent structural feature of 21 and its precursor 22 is the trans C16-C17 trisubstituted double bond. The particular relationship between the ethoxycarbonyl function and the A16 17 double bond in 22 is significant because it satisfies the structural prerequisite for the Johnson ortho ester Claisen rearrangement transform.2130 Mixed ketene acetal 23 thus emerges as the immediate... 

The Ireland-Claisen reaction of ( )-vinylsilanes has been applied to the stereoselective synthesis of syn- and c/nti-2-substituted 3-silyl alkcnoic acids. a R-2-Alkyl-3-silyl acids are prepared by rearrangement of ( )-silyl ketene acetals which are generated in situ from the kinetically formed (Z)-enolate of the corresponding propionate ester40. Chelation directs the stereochemistry of enolization of heteroelement-substituted acetates in such a way that the syn-diastereomers are invariably formed on rearrangement403. 

Ireland-Claisen rearrangement of silyl ketene acetals (31)... 

Ireland-Claisen rearrangement of O-allyl-O -trimethylsilyl ketene acetals... 

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. 

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. 

A. Claisen Rerrangements of Ketene Aminats and Imidates. A reaction that is related to the orthoester Claisen rearrangement utilizes an amide acetal, such as dimethylacetamide dimethyl acetal, in the exchange reaction with allylic alcohols.257 The products are y, 8-unsaturated amides. The stereochemistry of the reaction is analogous to the other variants of the Claisen rearrangement.258... 

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. 

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

A methylenation of cyclic carbonates such as 6/4-132 using dimethyltitanocene to give a ketene acetal, followed by a subsequent Claisen rearrangement, allowed the synthesis of medium-ring lactones such as 6/4-133 in good yields these are otherwise difficult to obtain. In this transformation, 6/4-133 is formed as a l l-mix-ture of the two atropisomers 6/4-133a and 6/4-133b (Scheme 6/4.33). The substrate... 

Sigmatropic rearrangement of A, 0-ketene acetals to yield Y,5-unsaturated amides. Since Eschenmoser was inspired by Meerwein s observations on the interchange of amide, the Eschenmoser-Claisen rearrangement is sometimes known as the Meerwein-Eschenmoser-Claisen rearrangement. 

Rearrangement of allyl trimethylsilyl ketene acetal, prepared by reaction of allylic ester enolates with trimethylsilyl chloride, to yield Y,5-unsaturated carboxylic a-cids. The Ireland-Claisen rearrangement seems to be advantageous to the other variants of the Claisen rearrangement in terms of E/Z geometry control and mild conditions. 

The Claisen rearrangement of lactonic enolates provides a new route to cycloalkenes. Cyclocitral was converted to the lactone (642) through a multistep sequence, the lactone deprotonated with LDA in THF at -78 °C, and the enolate quenched with f-butyldimethyl-chlorosilane (80JA6889, 6891). The crude ketene acetal (643) was heated at 110 °C for 10 h, and the product treated with fluoride ion to afford a single acid. Replacement of the quaternary carboxyl group by hydroxyl was accomplished through use of the carboxy inversion reaction (Scheme 147). The product (645) of this last reaction was identical with an authentic sample of widdrol in all respects excluding its optical rotation. 

To avoid the formation of ketenes by alkoxide elimination, ester enolates are often prepared at low temperatures. If unreactive alkyl halides are used, the addition of BU4NI to the reaction mixture can be beneficial [134]. Examples of the radical-mediated a-alkylation of support-bound a-haloesters are given in Table 5.4. Further methods for C-alkylating esters on insoluble supports include the Ireland-Claisen rearrangement of O-allyl ketene acetals (Entry 6, Table 13.16). Malonic esters and similar strongly C,H-acidic compounds have been C-alkylated with Merrifield resin [237,238]. 

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