title: Alkyne haloallylation [with Pd(II)] as a core strategy for macrocycle synthesis: a total synthesis of (-)-haterumalide NA/(-)-oocydin A.
abstract: The rarely used haloallylation reaction, first described by Kaneda and Teranishi in 1974, employs a Pd(II) catalyst to join an alkyne with an allylic halide to produce a 1-halo-1,4-diene subunit. It is shown here that functionalized and tertiary allylic chlorides perform well as substrates in this reaction under the action of PdCl2(PhCN)2 in THF solution. When the alkyne is added slowly to the reaction mixture, the two reactants can be used in a nearly equimolar ratio. This fact means (i) that reasonably complex pairs of alkyne and allylic halide substrates are tolerated and, therefore, (ii) that an intramolecular version of the reaction is suitable as a core strategy for complex molecule construction. The latter is demonstrated in the macrocyclization of 2b to 17b, which is the central step in the total synthesis of (-)-haterumalide NA/(-)-oocydin A (1) that is reported. The final key to the completion of the synthesis was the choice of the acid-labile PMB ester of 1 as the penultimate intermediate.
authors.affiliation: Department of Chemistry, University of Minnesota, Minneapolis, MN 55455, USA. hoye@chem.umn.edu
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Hoye
authors.forename: Jizhou
authors.initials: J
authors.lastname: Wang
mesh_terms: D000480:Alkynes / Q000737:chemistry*; D000498:Allyl Compounds / Q000737:chemistry*; D006846:Hydrocarbons, Halogenated / Q000737:chemistry; D007783:Lactones / Q000138:chemical synthesis*; D047028:Macrocyclic Compounds / Q000138:chemical synthesis*; D008968:Molecular Conformation; D009942:Organometallic Compounds / Q000737:chemistry; D010165:Palladium / Q000737:chemistry
chemical_list: D000480:Alkynes; D000498:Allyl Compounds; D006846:Hydrocarbons, Halogenated; D007783:Lactones; D047028:Macrocyclic Compounds; D009942:Organometallic Compounds; C403892:oocydin A; D010165:Palladium