One-Pot Synthesis of Diarylalkynes Using Palladium-Catalyzed Sonogashira Reaction and Decarboxylative Coupling of sp Carbon and sp2 Carbon

Reaction Scheme

Abstract

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.

Substrates

Procedure

SECONDARY AMINE ARYLATION: An oven-dried screw cap test tube was charged with a magnetic stir bar, RuPhos precatalyst 4 (2.3 mg, 0.005 mmol, 0.5 mol% or as indicated), RuPhos 2 (3.6 mg, 0.005 mmol, 0.5 mol% or as indicated), 1.0 mmol (if solid) aryl chloride (or, as indicated) and secondary amine (1.2 mmol) and Cs2CO3 (1.2 mmol or, as indicated). The tube was evacuated and refilled with argon (three times). Under a counterflow of argon, remaining liquid reagents were added, followed by 2 mL t-BuOH (or, as indiacted) by syringe. The tube was placed in a preheated oil bath at 85 �C (or, at indicated temperature) and the reaction mixture was stirred vigorously for 16 h (or, for indicated period of time). The reaction mixture was then cooled to room temperature, diluted with ethyl acetate, washed with water, dried over Na2SO4, concentrated in vacuo, and purified via the Biotage SP4 (silica- packed SNAP cartridge, KP-Sil, 10 g) using mixture of hexane and ethyl acetate.

Products

Materials

     
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