Base Effect on the Palladium Catalyzed α-Arylation of N-Benzyl-2-Piperidinones

Abstract

A very simple method for obtaining α-arylated N-benzyl-2-piperidinones in high yields is described. The use of s-BuLi as the base and Pd(dba)₂ as the catalyst are the key factors.

arylations - lactams - palladium - zinc - coupling

References

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Reaction Procedure for α-Arylation of N -Benzyl-2-Piperidinones: To a stirred solution of the N-benzyl-2-piperidone (1.1 mmol, 2.2 equiv) in THF (2 mL) at 0 °C was added a solution of s-BuLi (0.7 mL, 2.0 equiv). After 20 min, a solution of ZnCl₂ (0.150 g, 1.1 mmol, 2.2 equiv) in THF (1 mL) was added, and 20 min later the solution of zinc enolate was cannulated to a solution of 2-dicyclohexylphosphanyl-2′-(N,N-dimethylamino)biphenyl (L) (0.015 g, 37.5 µmol, 7.5 mol%), Pd(dba)₂ (0.014 g, 25.0 µmol, 5.0 mol%) and aryl bromide (0.5 mmol, 1.0 equiv) in THF (1 mL). The solution was then heated in an oil bath at 65 °C for 8 h, cooled to r.t., quenched with aq NH₄Cl and extracted with Et₂O. The organic phase was dried over MgSO₄, filtered and concentrated under reduced pressure. The residue was then purified by chromatography on silica gel using 80:20 or 70:30 cyclohexane-EtOAc.