Allylic ketene acetal 3,3 sigmatropic rearrangement

Heating of an allylic alcohol with an excess of trialkyl orthoacetate in the presence of trace amounts of a weak acid to give a mixed orthoester. The orthoester loses ethanol to generate the ketene acetal, which undergoes [3,3]-sigmatropic rearrangement to give a Y,5-unsaturated ester. 

Extremely useful ramifications of the Claisen rearrangement emerged with Johnson s discovery of the orthoester variant of this transformation. His approach (Scheme 2.156) involved the following sequence of steps, which were carried out in one reaction vessel (i) transesterification of the orthoester with an allylic alcohol to give 490 (ii) elimination to form the intermediate ketene acetal 491 and (iii) [3,3] sigmatropic rearrangement to yield the y, -unsaturated ester 492. The Johnson-Claisen procedure is properly considered to be one of the most efficient methods available to prepare y,(5-unsaturated esters such as 492. ° ... 

The interest generated by the Claisen rearrangement prompted the development of a considerable number of different versions of [3,3]-sigmatropic rearrangements. Thus, in 1972 Ireland reported the rearrangement of allyl trimethylsilyl ketene acetals to yield y,6-unsatura-ted carboxylic acids. ... 

The reaction outlined in O Scheme 59 is an example of a variant of the Claisen rearrangement of allyl ketene aminal (so-called Eschenmoser-Claisen rearrangement) [87], The reaction dose not require an acid catalyst glycal was just heated with dimethylacetamide dimethyl acetal to form ketene aminal, which underwent the sigmatropic rearrangement to form the corresponding )/,5-unsaturated amide. 

The Meerwein-Eschenmoser-Claisen rearrangement is one of the most useful pericyclic reactions. In its basic form, it involves the conversion of an allylic alcohol 1 to a ketene N, 0-acetal 2, which undergoes rapid [3,3]-sigmatropic rearrangement to yield a y,d-unsaturated amide 3 (Scheme 7.1). In accordance with the general electronic effects observed in Claisen rearrangements, the presence of an electron-donating amino substituent on the ketene acetal intermediate substantially increases the rate of the pericydic step. 

In the case of substituted ketene N,0-acetals formed through equilibria, for instance under the classical Eschenmoser conditions, the thermodynamically more stable (Z)-ketene N,0-acetal 61a is preferentially formed to avoid aUyUc strain between residue R and the bulky dimethylamine moiety (Scheme 7.22). Invoking a chair-shaped transition state, the anti-isomer is then formed from an (E)-allylic alcohol in the course of the sigmatropic rearrangement. Note that transition states 61a and 61b are diastereomers and not conformational isomers. 

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