title: Enantioselective copper-catalysed propargylic substitution: synthetic scope study and application in formal total syntheses of (+)-anisomycin and (-)-cytoxazone.
abstract: A copper catalyst with a chiral pyridine-2,6-bisoxazoline (pybox) ligand was used to convert a variety of propargylic esters with different side chains (R=Ar, Bn, alkyl) into their amine counterparts in very high yields and with good enantioselectivities (up to 90% enantiomeric excess (ee)). Different amine nucleophiles were applied in the reactions and the highest enantioselectivities were obtained for aniline and its analogues. Interestingly, some carbon nucleophiles could also be used and with indoles excellent ee values were obtained (up to 98% ee). The versatility of the propargylic amines obtained was demonstrated by their further elaboration to formal total syntheses of the antibiotic (+)-anisomycin and the cytokine modulator (-)-cytoxazone.
authors.affiliation: Biomolecular Synthesis Group, Van't Hoff Institute for Molecular Sciences, P.O. Box 94157, 1090GD Amsterdam, The Netherlands.
authors.forename: Remko J
authors.initials: RJ
authors.lastname: Detz
authors.forename: Zohar
authors.initials: Z
authors.lastname: Abiri
authors.forename: Remi
authors.initials: R
authors.lastname: le Griel
authors.forename: Henk
authors.initials: H
authors.lastname: Hiemstra
authors.forename: Jan H
authors.initials: JH
authors.lastname: van Maarseveen
mesh_terms: D000475:Alkenes / Q000737:chemistry*; D000588:Amines / Q000737:chemistry; D000841:Anisomycin / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D003300:Copper / Q000737:chemistry*; D008024:Ligands; D015394:Molecular Structure; D010080:Oxazoles / Q000138:chemical synthesis / Q000737:chemistry*; D011725:Pyridines / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D000475:Alkenes; D000588:Amines; D008024:Ligands; D010080:Oxazoles; D011725:Pyridines; C117832:cytoxazone; D000841:Anisomycin; D003300:Copper