Alpha-pyridylation of chiral amines via urea coupling, lithiation and rearrangement.
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, alpha-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.
Clayden
Jonathan
J
School of Chemistry, Univesity of Manchester, Oxford Road, Manchester M13 9PL, United Kingdom. clayden@man.ac.uk
Hennecke
Ulrich
U
D000588:Amines / Q000737:chemistry*; D002384:Catalysis; D008094:Lithium / Q000737:chemistry*; D008968:Molecular Conformation; D010165:Palladium / Q000737:chemistry; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D014508:Urea / Q000138:chemical synthesis / Q000737:chemistry*
D000588:Amines; D011725:Pyridines; D010165:Palladium; D014508:Urea; D008094:Lithium