Claisen reaction stereochemistry

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. 

The mechanism and stereochemistry of the orthoester Claisen rearrangement is analogous to the Cope rearrangement. The reaction is stereospecific with respect to the double bond present in the initial allylic alcohol. In acyclic molecules, the stereochemistry of the product can usually be predicted on the basis of a chairlike TS.233 When steric effects or ring geometry preclude a chairlike structure, the reaction can proceed through a boatlike TS.234... 

The stereochemistry of Ireland-Claisen rearrangements of cyclic compounds is sometimes indicative of reaction through a boat TS. For example, the major product from 2-cyclohexenyl propanoate is formed through a boat TS.244... 

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 Claisen rearrangement has been instrumental in the synthesis of a number of natural products.279-289 Many useful derivatives have been prepared using the Claisen-type rearrangement including enol ethers,290 amides,291-293 esters and orthoesters,294-296 acids,297-298 oxazolines,299 ketene acetals,300-301 and thioesters.302 Many of these variants use a cyclic primer to control relative and absolute stereochemistry. The Claisen and oxy Cope provide the best candidates for scale up as a result of the irreversible nature of these reactions. 

One classic example that confirms the preference of Claisen rearrangement for a chairlike transition state was provided by Hansen and others. In 1968, they investigated the Claisen rearrangement of the crotyl propenyl ethers 5a and 5b to examine the stereochemistry of the rearrangement in the gas phase at 160° C10 (Scheme l.V). Both the E,E- and Z,Z-isomers rearrange to afford a syn-isomer as the major product. The stereochemical outcome of the reaction can be explained... 

The Claisen ester condensation involves the only possible enolate attacking the only possible electrophilic carbonyl group. The stereochemistry of the ring junction cannot be changed by the reaction, and the two ester groups that started tram must end up trans in the product. 

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