Rearrangements, Claisen Eschenmoser variant

D-Mannitol (63) has been used for the synthesis of y-butyrolactones, making again use of a Claisen rearrangement as the key step (Scheme 10). The C2-symmetrical 1,4-diol 65, obtained from 63 via the alkene 64 [28], could be converted to 67 by applying the Eschenmoser-Claisen variant. Cyclization to 68 was readily achieved upon heating 67 in xylene, establishing two differ-... 

Whereas Eschenmoser and Johnson variants of the Claisen rearrangement utilize an excess of amide acetal and orthoester precursors, respectively, for generation of the vinyl ether functionality, the Carroll... 

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. 

Most [3,3]-sigmatropic rearrangements take place thermally, and the Cope, oxy-Cope and Claisen rearrangements are among the most important rearrangements in this class. Important variants of the Claisen rearrangement include the Johnson modification via orthoesters, the Eschenmoser modification via ketene N,O-acetals, the Ireland modification via ketene silylacetals and the Corey modification via boron ester enolates [696], The aza-Claisen rearrangement has also seen... 

Overall 1,4-diastcreoselection can be achieved by a sequential aldol addition-Claisen rearrangement. For example, alcohol 11 obtained in >50 1 diastereoselectivity from the reaction of crotonaldehyde and 2-methyl-2-trimethylsilyloxy-3-pentanone (9) via 10 was subjected to the Meerwein-Eschenmoser variant to give a 9 1 mixture of amides 12 and 13384. 

The Claisen rearrangement of bis-allyl vinyl ethers and related systems has been studied by several groups [98]. Modest to high levels of regioselectivity were obtained in the parent Claisen as well as Johnson, Eschenmoser and Ireland variants of the reaction. Parker and Farmar applied the ester enolate variant of the Ireland-Claisen rearrangement of a bis-aUylic ester to the synthesis of biflora-4,10(19),15-triene, using the rearrangement to install the 1,3-diene component for a subsequent intramolecular Diels-Alder reaction [99]. 

From a retrosynthetic point of view, the Meerwein-Eschenmoser-Claisen rearrangement shares the basic Claisen retron, a y,<5-unsaturated carbonyl compound, with other variants of the reaction. More specifically, its retron consists of a two-carbon chain branching off an allyhc stereocenter and terminating in an amide or a functional group derived thereof Such a motif can be readily identified in numerous natural products and other synthetic targets. 

Several variants of the Meerwein-Eschenmoser-Claisen rearrangement have been reported, which mostly differ in the way the ketene N,0-acetal intermediate is formed. Following a review of this aspect, the regjo- and stereoselectivity of the reaction is discussed. Finally, the usefulness of the reaction in the synthesis of complex target molecules is highlighted using selected examples, mostly from natural product syntheses. 

The Meerwein-Eschenmoser Claisen rearrangement is a variant of the Claisen process which is described by the thermal rearrangement of ketene... 

GradI, S. N., Kennedy-Smith, J. J., Kim, J., Trauner, D. A practical variant of the Claisen-Eschenmoser rearrangement synthesis of unsaturated morpholine amides. Syn/ett 2002, 411-414. 

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