Stereochemistry of the Claisen rearrangement

The stereochemistry of the Claisen rearrangement is generally predicted on the basis of conformational analysis in chairlike transition states (J) leading to the (E) substrate 49 and to the syn product. However, in this Pd(II)-catalyzed reaction, the (E) substrate 49 gave anti-50. This anomalous stereoselectivity is explained by six-membered ring boat transition states (K) via bidentate coordination to the palladium catalyst (Scheme 36). 

The stereochemistry of the Claisen rearrangement of allyl phenyl ethers has been examined. The new double bond is primarily trans whether it is formed from a CIS or a trans precursor. These results are accommodated by a chair-like cyclic transition state. For the two isomeric reactants, the preferred geometry for the transition state would be A and B, respectively. Both lead to a trans double bond in... 

Sucrow, W. Richter, W. Stereochemistry of the Claisen Rearrangement with 1-Dimethlamino-l-Methoxy-l-Propene Chem. Ber. 1971, 104, 3679-3688. 

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 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... 

To exploit the whole capacity of the Claisen rearrangement, appropriate methods for the preparation of the allyl vinyl ethers starting from allyl alcohols are necessary. The classical approach involves vinyl-ation with simple vinyl ethers or acetals. Unfortunately these methods fail with more complex systems and do not allow, except in the case of cyclic enol ethers, control of the stereochemistry of the substituted enol ether double bond. Until recently it was only possible to generate such substituted systems with appreciable stereocontrol via ketene N.O-acetals. Their preparation by addition of lyl alcohols to substituted ynamines can lead to adducts of either ( )- or (Z)-geometry, depending upon the conditions used (Scheme 60). 

In the total synthesis of (-)-furodysinin, aUyUc vinyl ether 85, which was prepared from (-i-)-hmonene oxide, was heated at high temperature to proceed the tandem Claisen rearrangement and an intramolecular ene reaction (Eq. 3.1.54) [67]. The route was actually designed to take advantage of the stereoselectivity of the Claisen rearrangement to establish the aldehyde side chain and the stereochemistry of the bicyclic system. At lower temperatures and shorter reaction times, the intermediary aldehyde could be isolated. 

In an independent study of the Claisen rearrangement of the E- and Z-crotyl esters of the 3-hydroxy butanoate, Kurth and Yu [39] isolated a mixture of two diastereomers each. NMR analysis of the 1,3-dioxanes, derived from the rearrangement products, was used to assign the stereochemistry at the 3,4 positions on the basis of coupling constants in the NMR spectra. To establish the stereochemistry at the 4,5 positions, ( )-botryodiplodin, a mycotoxin with both antibiotic and antileukemic properties, and its isomer 3-epibotryodiplodin were synthesized from the rearrangement products (Scheme 5.1.27) [39]. 

The synthesis of the cyclization substrate (99) began with addition of Grignard reagent 89 to methacrolein to provide allylic alcohol 90. A variation of the Claisen rearrangment, developed by the Johnson group for the synthesis of squalene and other terpenoids, was used to establish stereochemistry in trisubstituted olefin 91. 

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... 

Various nonracemic allenylstannanes have been prepared from nonracemic propargylic mesylates and (Bu3Sn)2CuLi. The stereochemistry of the displacement was shown to be anti by correlation with an allenic stannane prepared through Claisen orthoester rearrangement of a propargylic alcohol of known configuration (Scheme 33)80. 

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). 

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. 

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... 

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