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A new bench-stable trifluoromethylation reagent, phenyl bromodifluoroacetate, converts readily available alcohols to trifluoromethanes in a Cu-catalyzed deoxytrifluoromethylation reaction. This reaction streamlines access to target biologically active molecules, and should be useful for a variety of medicinal, agricultural, and materials chemists.

Trifluoroethylarenes are found in a variety of biologically active molecules, and strategies for accessing this substructure are important for developing therapeutic candidates and biological probes. Trifluoroethylarenes can be directly accessed via nucleophilic trifluoromethylation of benzylic electrophiles; however, current catalytic methods do not effectively transform electron-deficient substrates and heterocycles. To address this gap, we report a Cu-catalyzed decarboxylative trifluoromethylation of benzylic bromodifluoroacetates. To account for the tolerance of sensitive functional groups, we propose an inner-sphere mechanism of decarboxylation.

"Cu-CF3" species have been used historically for a broad spectrum of nucleophilic trifluoromethylation reactions. Although recent advancements have employed ligands to stabilize and harness the reactivity of this key organometallic intermediate, the ability of a ligand to differentiate a regiochemical outcome of a Cu-CF3-mediated or -catalyzed reaction has not been previously reported. Herein, we report the first example of a Cu-catalyzed trifluoromethylation reaction in which a ligand controls the regiochemical outcome. More specifically, we demonstrate the ability of bipyridyl-derived ligands to control the regioselectivity of the Cu-catalyzed nucleophilic trifluoromethylation reactions of propargyl electrophiles to generate (trifluoromethyl)allenes. This method provides a variety of di-, tri-, and tetrasubstituted (trifluoromethyl)allenes, which can be further modified to generate complex fluorinated substructures.

The development of new synthetic fluorination reactions has important implications in medicinal, agricultural, and materials chemistries. Given the prevalence and accessibility of alcohols, methods to convert alcohols to trifluoromethanes are desirable. However, this transformation typically requires four-step processes, specialty chemicals, and/or stoichiometric metals to access the trifluoromethyl-containing product. A two-step copper-catalyzed decarboxylative protocol for converting allylic alcohols to trifluoromethanes is reported. Preliminary mechanistic studies distinguish this reaction from previously reported Cu-mediated reactions.

Metal-catalyzed decarboxylative fluoroalkylation reactions enable the conversion of simple O-based substrates into biologically relevant fluorinated analogues. Herein, we present decarboxylative methods that facilitate the synthesis of trifluoromethyl- and difluoroketonecontaining products. We highlight key mechanistic aspects that are critical for efficient catalysis, and that inspired our thinking while developing the reactions. 1 Introduction 2 Copper-Catalyzed Decarboxylative Trifluoromethylation Reactions 2.1 Net Trifluoromethylation of Alcohols 2.2 Mechanism of Decarboxylation Impacts Functional-Group Tolerance 2.3 Allylic Trifluoromethylation Enabled by Activation Protocol 2.4 Generation of Iodide Intermediate Required for Benzylic Trifluoromethylation 2.5 Ligand-Controlled Regiodivergent Trifluoromethylation of Propargylic Electrophiles 2.6 Summary 3 Palladium-Catalyzed Decarboxylative Alkylation of α,α-Difluoroketone Enolates 3.1 Convergent Routes towards α,α-Difluoroketones 3.2 Palladium-Catalyzed Decarboxylative Benzylation of α,α-Difluoroketone Enolates 3.3 Palladium-Catalyzed Decarboxylative Allylation of α,α-Difluoroketone Enolates 3.4 Summary. [ABSTRACT FROM AUTHOR]

The development of efficient methods for accessing fluorinated functional groups is desirable. Herein, we report a twostep method that utilizes catalytic copper for the decarboxylative trifluoromethylation of propargyl bromodifluoroacetates is described. This protocol affords a mixture of propargyl trifluoromethanes and trifluoromethyl allenes. [ABSTRACT FROM AUTHOR]