title: Synthesis of ortho-haloaminoarenes by aryne insertion of nitrogen-halide bonds.
abstract: A rapid and general access to ortho-haloaminoarenes has been developed by aryne insertion into N-chloramine, N-bromoamine, and N-iodoamine bonds via two complementary protocols harnessing fluoride-promoted 1,2-elimination of ortho-trimethylsilyl aryltriflates. Typically, electron-deficient N-chloramines effectively react with aryne intermediates generated at elevated temperature with CsF, while less stable N-haloamines are found more efficient under milder, TBAF-mediated aryne formation at room temperature. Both protocols demonstrate a good level of regioselectivity and functional group tolerance. Efforts to elucidate the mechanism of N-X insertion are also discussed. The practical value of this transformation is highlighted by rapid synthesis of novel analogues of the antipsychotic cariprazine.
authors.affiliation: Department of Chemistry, Duke University , Durham, North Carolina 27708, United States.
authors.forename: Charles E
authors.initials: CE
authors.lastname: Hendrick
authors.forename: Qiu
authors.initials: Q
authors.lastname: Wang
mesh_terms: D000588:Amines / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D005459:Fluorides / Q000737:chemistry*; D006846:Hydrocarbons, Halogenated / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D009584:Nitrogen / Q000737:chemistry*; D010710:Phosphates / Q000737:chemistry*; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D000588:Amines; D006846:Hydrocarbons, Halogenated; D010710:Phosphates; D010879:Piperazines; C012980:fluorophosphate; C533287:cariprazine; D009584:Nitrogen; D005459:Fluorides