Carbodiimides react effectively with beta-aryl/alkyl-beta-hydroxy-alpha,alpha-difluorocarboxylic acids to afford a vast array of fully substituted gem-difluorodihydrouracils through a two step reaction sequence. In the first step, condensation between the two reactants leads in most cases to the formation of a mixture of the desired dihydrouracils and N-acylurea co-products. However, the latter could be easily recovered and efficiently converted into the target compounds. The sequence works well in very mild conditions (CH2Cl2, 20 degrees C) and the reaction resulted to be completely regioselective when asymmetric carbodiimides were used. When the N-acylurea derivatives are not sufficiently stable for isolation, the process could be done in a one-pot fashion leading to the direct formation of the desired dihydrouracils, although in lower yields.
- domino reaction
- alpha,beta-unsaturated carboxylic-acids
- pot sequential synthesis
- acyl migration
- peptide synthesis