Catalytic Asymmetric Synthesis of alpha-Trifluoromethylated Carbinols: A Case Study of Tertiary Propargylic Alcohols

Enantioenriched CF3-substituted tertiary alcohols have been applied in a broad range of chemical disciplines, including medicinal chemistry and agrochemistry. The widely prescribed anti-HIV pharmaceutical efavirenz is one particular example of the application of these chiral building blocks. Because the typical synthetic route to this small drug molecule involves the stoichiometric use of a chiral promoter, significant effort has been devoted to the development of catalytic alternatives for accessing this building block. In this Focus Review, we summarize the catalytic asymmetric synthesis of CF3-substituted tertiary propargylic alcohols based on three retrosynthetic approaches, namely one trifluoromethylation approach and two building-block strategies. The general challenges that are involved in the construction of a CF3-substituted tetrasubstituted stereogenic carbon species are highlighted and possible future directions in the field are discussed.