Failures of the aqueous solvent methodology

A major difficulty with the use of water as a solvent for the Claisen rearrangement is the solubility of the substrate. Hydrocarbon-like materials are not easily water-soluble even with addition of cosolvent. Two examples by the Fukumoto group serve to illustrate the point  

The first is an attempted Claisen rearrangement of a vinyl ether to give a precursor to aphidicolin [28], and the second is an attempted Claisen rearrangement of a vinyl ether to give an intermediate in the synthesis of stemodin [29]. 

Another notable failure is the attempt by Keese to effect the Claisen rearrangement to give a trans-fased bicyclo[3.3.0]octenyl system [30]  

In this case hydrolysis of the vinyl ether occurred before the 3,3-sigmatropic shift. 

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