Attention:

Certain features of Sigma-Aldrich.com will be down for maintenance the evening of Friday August 18th starting at 8:00 pm CDT until Saturday August 19th at 12:01 pm CDT.   Please note that you still have telephone and email access to our local offices. We apologize for any inconvenience.

Pd-Catalyzed Alkynylation of 2-Chloroacetates and 2-Chloroacetamides with Potassium Alkynyltrifluoroborates

Reaction Scheme

Abstract

A practical method for palladium-catalyzed cyanation of aryl halides using Pd/C is described. The new method can be applied to a variety of aryl bromide and active aryl chloride substrates to effect efficient conversions. The process features many advantages over existing cyanation conditions and the practical utility of the process has been demonstrated on scale.

Substrates

Procedure

To a round- bottomed flask were added 5-bromo-1H-indole (3) (1.0 g, 5.1 mmol), zinc cyanide (0.36 g; 3.1 mmol; 0.6 equiv) (Caution: highly toxic), 10 wt % Pd/C20 (108 mg; 0.10 mmol; 2 mol %), 1,1-bis(diphenylphosphino)ferrocene (dppf) (111 mg; 0.20 mmol; 4 mol %), and DMAC (8.5 mL). The resulting slurry was sparged with subsurface nitrogen for 10 min, and zinc formate dihydrate (79 mg; 0.51 mmol; 10 mol %) was added to the reaction mixture. The reaction mixture was again sparged with subsurface nitrogen for 10 min and was heated under nitrogen to 110 _C. Reaction conversion was monitored by HPLC. Upon completion, the reaction mixture was cooled to rt and diluted with 10 mL of EtOAc. The resulting slurry was filtered and the cake was rinsed with EtOAc (2 mL). The product was isolated by washing the filtrate with water (2 10 mL) and 5% NH4OH (1 10 mL). The organic layer was dried with Na2SO4. The volatile was removed in vacuo to give a residue, which was further purified by silica gel chromatography (EtOAc/heptanes) to provide 4 as a white solid (653 mg; 4.6 mmol; 90% yield).

Products

Materials

     
Related Links