title: The palladium-catalyzed trifluoromethylation of aryl chlorides.
abstract: The trifluoromethyl group can dramatically influence the properties of organic molecules, thereby increasing their applicability as pharmaceuticals, agrochemicals, or building blocks for organic materials. Despite the importance of this substituent, no general method exists for its installment onto functionalized aromatic substrates. Current methods either require the use of harsh reaction conditions or suffer from a limited substrate scope. Here we report the palladium-catalyzed trifluoromethylation of aryl chlorides under mild conditions, allowing the transformation of a wide range of substrates, including heterocycles, in excellent yields. The process tolerates functional groups such as esters, amides, ethers, acetals, nitriles, and tertiary amines and, therefore, should be applicable to late-stage modifications of advanced intermediates. We have also prepared all the putative intermediates in the catalytic cycle and demonstrated their viability in the process.
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA.
authors.forename: Eun Jin
authors.initials: EJ
authors.lastname: Cho
authors.forename: Todd D
authors.initials: TD
authors.lastname: Senecal
authors.forename: Tom
authors.initials: T
authors.lastname: Kinzel
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Donald A
authors.initials: DA
authors.lastname: Watson
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Buchwald
mesh_terms: D002384:Catalysis; D005464:Fluorobenzenes / Q000737:chemistry; D006843:Hydrocarbons, Chlorinated / Q000737:chemistry*; D006845:Hydrocarbons, Fluorinated / Q000138:chemical synthesis* / Q000737:chemistry*; D008024:Ligands; D008745:Methylation; D015394:Molecular Structure; D010084:Oxidation-Reduction; D010165:Palladium / Q000737:chemistry*
chemical_list: D005464:Fluorobenzenes; D006843:Hydrocarbons, Chlorinated; D006845:Hydrocarbons, Fluorinated; D008024:Ligands; C044697:benzotrifluoride; D010165:Palladium