Conjugate Addition Reactions ofN-Carbamoyl-4-Pyridones with Organometallic Reagents

Abstract

N-carbamoyl-4-pyridones undergo conjugate addition reactions with organocuprates and organozincates to afford 2-substituted-2,3-dihydro-4-pyridones providing a direct synthetic approach to substituted piperidines and piperidones. Good to excellent yields of conjugate adducts are achieved with lithium dialkylcuprates, alkylcyanocuprates, RLi/CuCN (0.3 equiv), and trialkylzincates with copper catalysis. Copper catalysis in the conjugate addition of Grignard reagents affords modest yields of conjugate adducts. An enantioenriched phosphoramidite ligand promotes the copper catalyzed conjugate addition of Et(2)Zn to a N-carbamoyl-4-pyridone with an er of 91.5:8.5.