title: A direct approach to amines with remote stereocentres by enantioselective CuH-catalysed reductive relay hydroamination.
abstract: Amines with remote stereocentres (stereocentres that are three or more bonds away from the C-N bond) are important structural elements in many pharmaceutical agents and natural products. However, previously reported methods to prepare these compounds in an enantioselective manner are indirect and require multistep synthesis. Here, we report a copper-hydride-catalysed, enantioselective synthesis of γ- or δ-chiral amines from readily available allylic alcohols, esters and ethers using a reductive relay hydroamination strategy (a net reductive process in which an amino group is installed at a site remote from the original carbon-carbon double bond). The protocol was suitable for substrates containing a wide range of functional groups and provided remote chiral amine products with high levels of regio- and enantioselectivity. Sequential amination of substrates containing several carbon-carbon double bonds could be achieved, demonstrating the high chemoselectivity of this process.
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Shaolin
authors.initials: S
authors.lastname: Zhu
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Nootaree
authors.initials: N
authors.lastname: Niljianskul
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Buchwald
mesh_terms: D000586:Amination / Q000502:physiology*; D000588:Amines / Q000737:chemistry*; D002384:Catalysis; D003300:Copper / Q000737:chemistry; D015394:Molecular Structure; D013237:Stereoisomerism
chemical_list: D000588:Amines; D003300:Copper