Stereochemistry Claisen rearrangment

N,O-acetal intermediate 172, y,<5-unsaturated amide 171. It is important to note that there is a correspondence between the stereochemistry at C-41 of the allylic alcohol substrate 173 and at C-37 of the amide product 171. Provided that the configuration of the hydroxyl-bearing carbon in 173 can be established as shown, then the subsequent suprafacial [3,3] sigmatropic rearrangement would ensure the stereospecific introduction of the C-37 side chain during the course of the Eschenmoser-Claisen rearrangement, stereochemistry is transferred from C-41 to C-37. Ketone 174, a potential intermediate for a synthesis of 173, could conceivably be fashioned in short order from epoxide 175. 

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 synthesis in Scheme 13.44 is also based on a carbohydrate-derived starting material. It controlled the stereochemistry at C(2) by means of the stereoselectivity of the Ireland-Claisen rearrangement in Step A (see Section 6.4.2.3). The ester enolate was formed under conditions in which the T -enolate is expected to predominate. Heating the resulting silyl enol ether gave a 9 1 preference for the expected stereoisomer. The... 

The stereochemistry of the silyl enol ether Claisen rearrangement is controlled not only by the stereochemistry of the double bond in the allyhc alcohol but also by the stereochemistry of the silyl enol ether. For the chair transition state, the configuration at the newly formed C—C bond is predicted to be determined by the E- or Z-configuration of the silyl enol ether. 

Chirality transfer also belongs to this class of methods. Thus, the configuration of (S)-(E)-Ar,jV-dimethyl-3-trimethylsilyl-4-hexenamide [(S)-(Zi)-2 on p 422] was solely assigned81 on the basis of the established stereochemistry of the Eschenmoser Claisen rearrangement (see P 475). 

The use of the Claisen rearrangement and several other methods for the stereoselective synthesis of trisubstituted olefins has been reviewed.6 In allyl vinyl ethers of type A, the stereochemistry of the rearrangement is determined largely... 

In fact, the allylation was carried out by the Claisen rearrangement (chapter 35) and the cycloaddition on the alcohol 18 catalysed by Cu(I). The product was a mixture of the major isomer 23 with some of the exo-alcohol (OH up as drawn). This is irrelevant as both alcohols oxidise to the ketone 16. The stereochemistry at the ring junction can only be cis. 

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. 

Claisen rearrangements, in 2-allyloxythia-zole, kinetic siudy. 410 stereochemistry. 410 Qeavage. of 2-acetylimino-4-thjazolines. 

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... 

Alkene stereochemistry in the Claisen rearrangement comes from a chair-like transition state... 

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