Advances in Catalytic Enantioselective Fluorination, Mono-, Di-, and Trifluoromethylation, and Trifluoromethylthiolation Reactions

1. INTRODUCTION Despite being largely absent from natural products and biological processes, fluorine plays a conspicuous and increasingly important role within pharmaceuticals and agro-chemicals, as well as in materials science. 1a−c Indeed, as many as 35% of agrochemicals and 20% of pharmaceuticals on the market contain fluorine. 1d Fluorine is the most electronegative element in the periodic table, and the introduction of one or more fluorine atoms into a molecule can result in greatly perturbed properties. Fluorine substituents can potentially impact a number of variables, such as the acidity or basicity of neighboring groups, dipole moment, and properties such as lipophilicity, metabolic stability, and bioavailability. The multitude of effects that can arise from the introduction of fluorine in small molecules in the context of medicinal chemistry has been extensively discussed elsewhere.