title: Copper-catalysed selective hydroamination reactions of alkynes.
abstract: The development of selective reactions that utilize easily available and abundant precursors for the efficient synthesis of amines is a long-standing goal of chemical research. Despite the centrality of amines in a number of important research areas, including medicinal chemistry, total synthesis and materials science, a general, selective and step-efficient synthesis of amines is still needed. Here, we describe a set of mild catalytic conditions utilizing a single copper-based catalyst that enables the direct preparation of three distinct and important amine classes (enamines, α-chiral branched alkylamines and linear alkylamines) from readily available alkyne starting materials with high levels of chemo-, regio- and stereoselectivity. This methodology was applied to the asymmetric synthesis of rivastigmine and the formal synthesis of several other pharmaceutical agents, including duloxetine, atomoxetine, fluoxetine and tolterodine.
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Shi-Liang
authors.initials: SL
authors.lastname: Shi
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: D000480:Alkynes / Q000737:chemistry*; D000586:Amination; D000588:Amines / Q000138:chemical synthesis*; D000069445:Atomoxetine Hydrochloride; D001559:Benzhydryl Compounds / Q000138:chemical synthesis; D002384:Catalysis; D003300:Copper / Q000737:chemistry*; D003408:Cresols / Q000138:chemical synthesis; D000068736:Duloxetine Hydrochloride; D005473:Fluoxetine / Q000138:chemical synthesis; D010665:Phenylpropanolamine / Q000138:chemical synthesis; D011437:Propylamines / Q000138:chemical synthesis; D013237:Stereoisomerism; D013876:Thiophenes / Q000138:chemical synthesis; D000068737:Tolterodine Tartrate
chemical_list: D000480:Alkynes; D000588:Amines; D001559:Benzhydryl Compounds; D003408:Cresols; D011437:Propylamines; D013876:Thiophenes; D005473:Fluoxetine; D010665:Phenylpropanolamine; D000069445:Atomoxetine Hydrochloride; D000068737:Tolterodine Tartrate; D003300:Copper; D000068736:Duloxetine Hydrochloride