title: A steric tethering approach enables palladium-catalysed C-H activation of primary amino alcohols.
abstract: Aliphatic primary amines are a class of chemical feedstock essential to the synthesis of higher-order nitrogen-containing molecules, commonly found in biologically active compounds and pharmaceutical agents. New methods for the construction of complex amines remain a continuous challenge to synthetic chemists. Here, we outline a general palladium-catalysed strategy for the functionalization of aliphatic C-H bonds within amino alcohols, an important class of small molecule. Central to this strategy is the temporary conversion of catalytically incompatible primary amino alcohols into hindered secondary amines that are capable of undergoing a sterically promoted palladium-catalysed C-H activation. Furthermore, a hydrogen bond between amine and catalyst intensifies interactions around the palladium and orients the aliphatic amine substituents in an ideal geometry for C-H activation. This catalytic method directly transforms simple, easily accessible amines into highly substituted, functionally concentrated and structurally diverse products, and can streamline the synthesis of biologically important amine-containing molecules.
authors.affiliation: Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK.
authors.forename: Jonas
authors.initials: J
authors.lastname: Calleja
authors.affiliation: Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK.
authors.forename: Daniel
authors.identifier: http://orcid.org/0000-0002-8703-8778
authors.initials: D
authors.lastname: Pla
authors.affiliation: Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK.
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Gorman
authors.affiliation: Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK.
authors.forename: Victoriano
authors.initials: V
authors.lastname: Domingo
authors.affiliation: Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Haffemayer
authors.affiliation: Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Gaunt
mesh_terms: D000588:Amines / Q000737:chemistry*; D000605:Amino Alcohols / Q000737:chemistry*; D002384:Catalysis; D008958:Models, Molecular; D015394:Molecular Structure; D010165:Palladium / Q000737:chemistry*
chemical_list: D000588:Amines; D000605:Amino Alcohols; D010165:Palladium