title: A Two-Component Alkyne Metathesis Catalyst System with an Improved Substrate Scope and Functional Group Tolerance: Development and Applications to Natural Product Synthesis.
abstract: Although molybdenum alkylidyne complexes such as 1 endowed with triarylsilanolate ligands are excellent catalysts for alkyne metathesis, they can encounter limitations when (multiple) protic sites are present in a given substrate and/or when forcing conditions are necessary. In such cases, a catalyst formed in situ upon mixing of the trisamidomolybenum alkylidyne complex 3 and the readily available trisilanol derivatives 8 or 11 shows significantly better performance. This two-component system worked well for a series of model compounds comprising primary, secondary or phenolic -OH groups, as well as for a set of challenging (bis)propargylic substrates. Its remarkable efficiency is also evident from applications to the total syntheses of manshurolide, a highly strained sesquiterpene lactone with kinase inhibitory activity, and the structurally demanding immunosuppressive cyclodiyne ivorenolide A; in either case, the standard catalyst 1 largely failed to effect the critical macrocyclization, whereas the two-component system was fully operative. A study directed toward the quinolizidine alkaloid lythrancepine I features yet another instructive example, in that a triyne substrate was metathesized with the help of 3/11 such that two of the triple bonds participated in ring closure, while the third one passed uncompromised. As a spin-off of this project, a much improved ruthenium catalyst for the redox isomerization of propargyl alcohols to the corresponding enones was developed.
authors.affiliation: Max-Planck-Institut für Kohlenforschung, 45470, Mülheim/Ruhr, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Schaubach
authors.affiliation: Max-Planck-Institut für Kohlenforschung, 45470, Mülheim/Ruhr, Germany.
authors.forename: Konrad
authors.initials: K
authors.lastname: Gebauer
authors.affiliation: Max-Planck-Institut für Kohlenforschung, 45470, Mülheim/Ruhr, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Ungeheuer
authors.affiliation: Max-Planck-Institut für Kohlenforschung, 45470, Mülheim/Ruhr, Germany.
authors.forename: Laura
authors.initials: L
authors.lastname: Hoffmeister
authors.affiliation: Max-Planck-Institut für Kohlenforschung, 45470, Mülheim/Ruhr, Germany.
authors.forename: Marina K
authors.initials: MK
authors.lastname: Ilg
authors.affiliation: Max-Planck-Institut für Kohlenforschung, 45470, Mülheim/Ruhr, Germany.
authors.forename: Conny
authors.initials: C
authors.lastname: Wirtz
authors.affiliation: Max-Planck-Institut für Kohlenforschung, 45470, Mülheim/Ruhr, Germany. fuerstner@kofo.mpg.de.
authors.forename: Alois
authors.initials: A
authors.lastname: Fürstner
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis / Q000737:chemistry; D000480:Alkynes / Q000737:chemistry*; D001688:Biological Products / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry; D018360:Crystallography, X-Ray; D018942:Macrolides / Q000138:chemical synthesis / Q000737:chemistry; D008968:Molecular Conformation; D008982:Molybdenum / Q000737:chemistry*
chemical_list: D000470:Alkaloids; D000480:Alkynes; D001688:Biological Products; D056831:Coordination Complexes; D018942:Macrolides; C581291:ivorenolide A; C032336:lythranidine; D008982:Molybdenum
keywords: alkyne metathesis; molybdenum; natural products; propargyl alcohols; redox isomerization