title: Palladium-Catalyzed Arylation of Fluoroalkylamines.
abstract: We report the synthesis of fluorinated anilines by palladium-catalyzed coupling of fluoroalkylamines with aryl bromides and aryl chlorides. The products of these reactions are valuable because anilines typically require the presence of an electron-withdrawing substituent on nitrogen to suppress aerobic or metabolic oxidation, and the fluoroalkyl groups have steric properties and polarity distinct from those of more common electron-withdrawing amide and sulfonamide units. The fluoroalkylaniline products are unstable under typical conditions for C-N coupling reactions (heat and strong base). However, the reactions conducted with the weaker base KOPh, which has rarely been used in cross-coupling to form C-N bonds, occurred in high yield in the presence of a catalyst derived from commercially available AdBippyPhos and [Pd(allyl)Cl]2. Under these conditions, the reactions occur with low catalyst loadings (<0.50 mol % for most substrates) and tolerate the presence of various functional groups that react with the strong bases that are typically used in Pd-catalyzed C-N cross-coupling reactions of aryl halides. The resting state of the catalyst is the phenoxide complex, (BippyPhosPd(Ar)OPh); due to the electron-withdrawing property of the fluoroalkyl substituent, the turnover-limiting step of the reaction is reductive elimination to form the C-N bond.
authors.affiliation: Department of Chemistry, University of California, Berkeley, California 94720, United States.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Brusoe
authors.affiliation: Department of Chemistry, University of California, Berkeley, California 94720, United States.
authors.forename: John F
authors.initials: JF
authors.lastname: Hartwig
mesh_terms: D000577:Amides / Q000737:chemistry; D000588:Amines / Q000737:chemistry*; D000814:Aniline Compounds / Q000737:chemistry; D001965:Bromides / Q000737:chemistry; D002244:Carbon / Q000737:chemistry; D002384:Catalysis; D002625:Chemistry, Organic / Q000379:methods*; D002712:Chlorides / Q000737:chemistry; D004583:Electrons; D000077613:Etoricoxib; D005461:Fluorine / Q000737:chemistry*; D007700:Kinetics; D008968:Molecular Conformation; D015394:Molecular Structure; D009584:Nitrogen / Q000737:chemistry; D010165:Palladium / Q000737:chemistry*; D019800:Phenol / Q000737:chemistry; D011725:Pyridines / Q000737:chemistry; D013450:Sulfones / Q000737:chemistry
chemical_list: D000577:Amides; D000588:Amines; D000814:Aniline Compounds; D001965:Bromides; D002712:Chlorides; D011725:Pyridines; D013450:Sulfones; D005461:Fluorine; D019800:Phenol; D010165:Palladium; D002244:Carbon; D009584:Nitrogen; C023650:aniline; D000077613:Etoricoxib