Process, continuous Claisen rearrangement

There has been a continuing effort to make the Baylis-Hillman reaction a catalytic asymmetric process. Scott Schnauss of Boston University recently reported (J. Am. Chem. Soc. 125 12094, 2003) an elegant solution to this problem, based on the use of Binol-derived Bronsted acids as catalysts. The product hydroxy enones such as 6 are interesting in themselves, and also as substrates for further transformation, for instance by Claisen rearrangement. 

From 1964 to 1990, the discovery of highly versatile stereoselective variants supported a period of impressive growth in the number of synthetic efforts which employ a Claisen rearrangement for a key carbon-carbon bond forming process (Table 1), This increase in experimental applicaticms was accompanied by a continuous interest in mechanistic analysis and theoretical understanding of the reaction. 

The ortho-ester Claisen rearrangement continues to provide a versatile method for the preparation of unsaturated esters. Reaction of trimethyl-methoxyorthoacetate with an allyl alcohol furnishes a-methoxy-Y,d-unsaturated esters in 22—55% yields. A stereospecific synthesis of both enantiomers of the insect pheromone methyl E-2,4,5-tetradecatrienoate involves the conversion of the R-acetylenic alcohol (65) (Scheme 53) into the R-allenic ester (66) as its key step. This process was repeated with the 5-alcohol to provide the enantiomer of (66). The optically active erythro-alcohol (67), readily available... 

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