Axial chirality is a key feature of many important organic molecules, such as biologically active compounds, stereogenic ligands and optically pure materials. Significant efforts in the field of the atropisomeric synthesis of biaryls have hence been undertaken over the past decade. Several major improvements of the already known methods to build up such chiral backbones (e.g. oxidative couplings and stereoselective Suzuki–Miyaura arylations) have been achieved and, in parallel, novel concepts have emerged enabling unprecedented synthetic routes toward molecules of this kind. These outstanding steps further unlocked the door to the preparation of previously difficult-to-access precursors of privileged ligands like BINOL, BINAM, QUINAP and many other molecules of interest.

The ever-growing number of fluorinated compounds in medicinal and agrochemical applications has led to a remarkable positive emulation in research. The last few years have been the witness of several advances in the search of more effective and user-friendlier methods for the introduction of fluorine as substituent or of fluorinated groups on various structures. In particular, the synthesis of trifluoromethyl ethers and thioethers is receiving increasing attention due to the peculiar properties of the OCF₃ and SCF₃ groups. This review will cover the different methods for the preparation of trifluoromethyl ethers and thioethers, and will emphasize on the most recent developments, including the use of catalytic methods or of methodologies for trifluoromethylation or trifluoromethanesulfanylation.

Trifluoromethyl ethers – synthesis and properties of an unusual substituent

In the last few years, transition metal-mediated reactions have joined the toolbox of chemists working in the field of fluorination for Life-Science oriented research. The successful execution of transition metal-catalyzed carbon–fluorine bond formation has become a landmark achievement in fluorine chemistry. This rapidly growing research field has been the subject of some excellent reviews. Our approach focuses exclusively on transition metal-catalyzed reactions that allow the introduction of –CFH₂, –CF₂H, –C_nF_2n+1 and –SCF₃ groups onto sp² carbon atoms. Transformations are discussed according to the reaction-type and the metal employed. The review will not extend to conventional non-transition metal methods to these fluorinated groups.