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α-Pyridinylation of Chiral Amines via Urea Coupling, Lithiation and Rearrangement: Synthesis of α-Arylated Nicotine Analogues

  • July 22, 2008

2-, 3- and 4-Bromopyridine, along with other brominated electron-deficient arenes, undergo palladium-catalyzed coupling with ureas of structure RNMeCONHMe. Where R is a chiral, α-substituted benzyl group, treatment with LDA leads to a benzylic organolithium which undergoes rearrangement with stereospecific and regiospecific transfer of the pyridyl group, generating a quaternary stereogenic center with high enantioselectivity. Alcoholysis of the urea under neutral conditions reveals the pyridyl amine.


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