Rational and Predictable Chemoselective Synthesis of Oligoamines via Buchwald-Hartwig Amination of (Hetero)Aryl Chlorides Employing Mor-DalPhos

Reaction Scheme


We report our studies on the use of two catalyst systems, based on the ligands BrettPhos and RuPhos, which provide the widest scope for Pd-catalyzed C-N cross-coupling reactions to date. Often low catalyst loadings and short reaction times can be used with functionalized aryl and heteroaryl coupling partners. The reactions are highly robust and can be set up and performed without the use of a glovebox. These catalysts should find wide application in the synthesis of complex molecules including pharmaceuticals, natural products and functional materials.



PRIMARY AMINES - PROTIC SUBSTRATES: An oven-dried screw cap test tube was charged with a magnetic stir bar, BrettPhos precatalyst 3 (2 mg, 0.0025 mmol, 0.25 mol% or as indicated), BrettPhos 1 (1.3 mg, 0.0025 mmol, 0.25 mol% or as indicated), 1.0 mmol (if solid) aryl chloride (or, as indicated) and primary amine (1.2 mmol). The tube was evacuated and refilled with argon (three times). Under a counterflow of argon, remaining liquid reagents were added, followed by 2 mL (or, as indicated) 1,4-dioxane solution (or, as indicated) of LHMDS (2.4 mmol or, as indicated) by syringe. The tube was placed in a preheated oil bath at 100 �C (or, at indicated temperature) and the reaction mixture was stirred vigorously for 2 h (or, for indicated period of time). The reaction mixture was then cooled to room temperature, diluted with CH2Cl2, washed with water, dried over Na2SO2, concentrated in vacuo, and purified via the Biotage SP4 (silica- packed SNAP cartridge, KP-Sil, 10 g) eluting with a mixture of hexane and ethyl acetate.



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