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Chiral metal complexes catalyze enantioselective carbonyl propargylation via reductive coupling or as hydrogen auto‐transfer processes, in which reactant alcohols serve dually as reductant and carbonyl proelectrophile. Unlike classical propargylation protocols, which rely on allenylmetal reagents or metallic reductants (e. g. NHK reactions), reductive protocols for carbonyl propargylation can occur in the absence of stoichiometric metals, precluding generation of metallic byproducts. Propargylations of this type exploit both enyne and propargyl halide pronucleophiles. Dual function alcohols: Chiral metal complexes catalyze enantioselective carbonyl propargylation via reductive coupling or as hydrogen auto‐transfer processes, in which reactant alcohols serve dually as reductant and carbonyl proelectrophile. Unlike classical propargylation protocols, which rely on allenylmetal reagents or metallic reductants (e. g. NHK reactions), reductive protocols for carbonyl propargylation can occur in the absence of stoichiometric metals, precluding generation of metallic byproducts. Propargylations of this type exploit both enyne and propargyl halide pronucleophiles. [ABSTRACT FROM AUTHOR]

Heme-based tryptophan dioxygenases are established immunosuppressive metalloproteins with significant biomedical interest. Here, we synthesized two mechanistic probes to specifically test if the a-amino group of the substrate directly participates in a critical step of the O atom transfer during catalysis in human tryptophan 2,3-dioxygenase (TDO). Substitution of the nitrogen atom of the substrate to a carbon (probe 1) or oxygen (probe 2) slowed the catalytic step following the first O atom transfer such that transferring the second O atom becomes less likely to occur, although the dioxygenated products were observed with both probes. A monooxygenated product was also produced from probe 2 in a significant quantity. Analysis of this new product by HPLC coupled UV-vis spectroscopy, high-resolution mass spectrometry, ¹H NMR, 13C NMR, HSQC, HMBC, and infrared (IR) spectroscopies concluded that this monooxygenated product is a furoindoline compound derived from an unstable epoxyindole intermediate. These results prove that small molecules can manipulate the stepwise O atom transfer reaction of TDO and provide a showcase for a tunable mechanism by synthetic compounds. The product analysis results corroborate the presence of a substrate-based epoxyindole intermediate during catalysis and provide the first substantial experimental evidence for the involvement of the substrate a-amino group in the epoxide ring-opening step during catalysis. This combined synthetic, biochemical, and biophysical study establishes the catalytic role of the a-amino group of the substrate during the O atom transfer reactions and thus represents a substantial advance to the mechanistic comprehension of the heme-based tryptophan dioxygenases. [ABSTRACT FROM AUTHOR]

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]

The reaction can be scaled up. [ABSTRACT FROM AUTHOR]

Fluorinated organic compounds have a long history in medicinal chemistry, and synthetic methods to access target fluorinated compounds are undergoing a revolution. One powerful strategy for the installation of fluorinecontaining functional groups includes decarboxylative reactions. Benefits of decarboxylative approaches potentially include: 1) readily available substrates or reagents 2) mild reaction conditions; 3) simplified purification. This focus review highlights the applications of decarboxylation strategies for fluorination reactions to access compounds with biomedical potential. The manuscript highlights on two general strategies, fluorination by decarboxylative reagents and by decarboxylation of substrates. Where relevant, examples of medicinally useful compounds that can be accessed using these strategies are highlighted.