Synthesis of aromatic compounds containing a 1,1-dialkyl-2-trifluoromethyl group, a bioisostere of the tert-alkyl moiety

1,1-Dialkyl-2-perfluoroalkyl compounds, which are potential metabolically stable bioisosteres of the tert-alkyl moiety, have been synthesized from the corresponding tertiary alcohols using titanium (IV) chloride-dimethylzinc or trimethylaluminium as the source of the methyl group. The synthetic methods proved to be versatile for synthesizing 1,1-dimethyl-2,2,2-trifluoroethyl compounds and analogs, including compounds containing aromatic and heterocyclic rings.