title: Ligand-Controlled Regioselective Copper-Catalyzed Trifluoromethylation To Generate (Trifluoromethyl)allenes.
abstract: "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.
authors.affiliation: Department of Medicinal Chemistry, The University of Kansas, Lawrence, Kansas 66045, United States.
authors.forename: Brett R
authors.initials: BR
authors.lastname: Ambler
authors.affiliation: Department of Medicinal Chemistry, The University of Kansas, Lawrence, Kansas 66045, United States.
authors.forename: Santosh
authors.initials: S
authors.lastname: Peddi
authors.affiliation: Department of Medicinal Chemistry, The University of Kansas, Lawrence, Kansas 66045, United States.
authors.forename: Ryan A
authors.initials: RA
authors.lastname: Altman
mesh_terms: D000466:Alkadienes / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D003300:Copper / Q000737:chemistry*; D006845:Hydrocarbons, Fluorinated / Q000138:chemical synthesis* / Q000737:chemistry; D008024:Ligands; D015394:Molecular Structure; D013237:Stereoisomerism
chemical_list: D000466:Alkadienes; D006845:Hydrocarbons, Fluorinated; D008024:Ligands; C025947:propadiene; D003300:Copper