Enantiopure quaternary alpha-trifluoromethyl-alpha-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 alpha-trifluoromethylated alpha-alkoxyaldehydes. This procedure was applied to the preparation of a series of enantiopure aryl, heteroaryl, and alkyl alpha-trifluoromethyl-alpha-alkoxyaldehydes.