Enantiopure Quaternary α-Trifluoromethyl-α-alkoxyaldehydes from l-Tartaric Acid Derived Ketoamides

The diastereoselective nucleophilic trifluoromethylation of a range of ketoamides derived from l-tartaric acid has been studied. TMSCF3 in the presence of a catalytic amount of K2CO3 in DMF has been identified as the conditions leading to the highest diastereoselectivities. A sequential one-pot reaction trifluoromethylation−etherification of the trifluoromethylcarbinol has been developed. Only one further one-pot reaction, ketal hydrolysis−oxidative cleavage, led to the final α-trifluoromethylated α-alkoxyaldehydes. This procedure was applied to the preparation of a series of enantiopure aryl, heteroaryl, and alkyl α-trifluoromethyl-α-alkoxyaldehydes