Tandem beta-alkylation-alpha-arylation of amines by carbolithiation and rearrangement of N-carbamoyl enamines (vinyl ureas).
Organolithiums add in an umpolung fashion to the beta-carbon of N-carbamoyl enamines (N-vinyl ureas). The reaction proceeds with syn diastereospecificity and provides urea-stabilized, configurationally defined organolithiums. Facilitated by coordinating solvents (THF or DMPU), these undergo intramolecular attack on an N'-aryl group, resulting in retentive arylation of the organolithium and hence overall addition of an alkyl or aryl group to both carbon atoms of the urea-substituted alkene. Facile deprotection in hot butanol permits the rapid, multicomponent construction of heavily substituted amines.
Clayden
Jonathan
J
School of Chemistry, University of Manchester, Oxford Road, Manchester M13 9PL, UK. clayden@man.ac.uk
Donnard
Morgan
M
Lefranc
Julien
J
Minassi
Alberto
A
Tetlow
Daniel J
DJ
D000478:Alkylation; D000588:Amines / Q000737:chemistry*; D008094:Lithium / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D013237:Stereoisomerism; D014508:Urea / Q000737:chemistry*
D000588:Amines; D014508:Urea; D008094:Lithium