McGuire Ryan T, Yadav Arun A, Stradiotto Mark
Department of Chemistry, Dalhousie University, Halifax, Nova Scotia, B3H 4R2, Canada.
Paraza Pharma, Inc., 2525 Avenue Marie-Curie, Montreal, Quebec, H4S 2E1, Canada.
Angew Chem Int Ed Engl. 2021 Feb 19;60(8):4080-4084. doi: 10.1002/anie.202014340. Epub 2020 Dec 23.
The Ni-catalyzed N-arylation of β-fluoroalkylamines with broad scope is reported for the first time. Use of the air-stable pre-catalyst (PAd2-DalPhos)Ni(o-tol)Cl allows for reactions to be conducted at room temperature (25 °C, NaOtBu), or by use of a commercially available dual-base system (100 °C, DBU/NaOTf), to circumvent decomposition of the N-(β-fluoroalkyl)aniline product. The mild protocols disclosed herein feature broad (hetero)aryl (pseudo)halide scope (X=Cl, Br, I, and for the first time phenol-derived electrophiles), encompassing base-sensitive substrates and enantioretentive transformations, in a manner that is unmatched by any previously reported catalyst system.
首次报道了镍催化的β-氟烷基胺的N-芳基化反应，该反应具有广泛的底物范围。使用空气稳定的预催化剂（PAd2-DalPhos）Ni（邻甲苯）Cl，反应可以在室温下（25°C，NaOtBu）进行，或者使用市售的双碱体系（100°C，DBU/NaOTf）进行，以避免N-（β-氟烷基）苯胺产物的分解。本文公开的温和反应方案具有广泛的（杂）芳基（拟）卤化物范围（X = Cl、Br、I，并且首次包括酚衍生的亲电试剂），涵盖了对碱敏感的底物和对映体保留转化，这是任何先前报道的催化体系都无法比拟的。
