Synthesis of enantiopure trifluoromethyl building blocks via a highly chemo- and diastereoselective nucleophilic trifluoromethylation of tartaric acid-derived diketones.

A highly diastereoselective nucleophilic mono(trifluoromethylation) of a tartaric acid-based diketone, using trifluoromethyl(trimethyl)silane, afforded the corresponding gamma-keto trifluoromethylcarbinol. The scope and limitation of this reaction was studied. The acidic removal of the acetonide moiety protecting the two hydroxyl groups of the adducts was unsuccessful. Bis(O-methylation) of the aromatic derivatives under basic conditions, followed by acidic hydrolysis and oxidative cleavage, led to two different enantiopure products: an alpha-aryl-alpha-methoxy-alpha-trifluoromethyl ethanal and an alpha-aryl-alpha-methoxycarboxylic acid. The overall process is eventually an interesting way to convert one natural chiral raw material into two functionalized enantiopure building blocks including a trifluoromethyl one.