Visible Light-Mediated (Hetero)aryl Amination Using Ni(II) Salts and Photoredox Catalysis in Flow: A Synthesis of Tetracaine
Boyoung Y. Park, Michael T. Pirnot, Stephen L. Buchwald
Abstract
We report a visible light-mediated flow process for C-N cross-coupling of (hetero)aryl halides with a variety of amine coupling partners through the use of a photoredox/nickel dual catalyst system. Compared to the method in batch, this flow process enables a broader substrate scope, including less-activated (hetero)aryl bromides and electron-deficient (hetero)aryl chlorides, and significantly reduced reaction times (10 to 100 min). Furthermore, scale up of the reaction, demonstrated through the synthesis of tetracaine, is easily achieved, delivering the C-N cross-coupled products in consistently high yield of 84% on up to a 10 mmol scale.
Topics & Concepts
ChemistryArylAminationCatalysisYield (engineering)Substrate (aquarium)Amine gas treatingPhotoredox catalysisMicroreactorCombinatorial chemistryPhotochemistryCoupling reactionHalideOrganic chemistryPhotocatalysisGeologyOceanographyMaterials scienceMetallurgyAlkylRadical Photochemical ReactionsCatalytic Cross-Coupling ReactionsAdvanced Photocatalysis Techniques