title: Cascade cyclizations of acyclic and macrocyclic alkynones: studies toward the synthesis of phomactin A.
abstract: A study of the reactivity and diastereoselectivity of the Lewis acid promoted cascade cyclizations of both acyclic and macrocyclic alkynones is described. In these reactions, a β-iodoallenolate intermediate is generated via conjugate addition of iodide to an alkynone followed by an intramolecular aldol reaction with a tethered aldehyde to afford a cyclohexenyl alcohol. The Lewis acid magnesium iodide (MgI2) was found to promote irreversible ring closure, while cyclizations using BF3·OEt2 as promoter occurred reversibly. For both acyclic and macrocyclic alkynones, high diastereoselectivity was observed in the intramolecular aldol reaction. The MgI2 protocol for cyclization was applied to the synthesis of advanced intermediates relevant to the synthesis of phomactin natural products, during which a novel transannular cation-olefin cyclization was observed. DFT calculations were conducted to analyze the mechanism of this unusual MgI2-promoted process.
authors.affiliation: Department of Chemistry, University of Rochester , Rochester, New York 14627, United States.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Ciesielski
authors.forename: Vincent
authors.initials: V
authors.lastname: Gandon
authors.forename: Alison J
authors.initials: AJ
authors.lastname: Frontier
mesh_terms: D001688:Biological Products / Q000737:chemistry*; D003500:Cyclization; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis* / Q000737:chemistry; D007454:Iodides / Q000737:chemistry; D007659:Ketones / Q000737:chemistry*; D058116:Lewis Acids / Q000737:chemistry; D047028:Macrocyclic Compounds / Q000737:chemistry*; D017616:Magnesium Compounds / Q000737:chemistry; D015394:Molecular Structure; D013237:Stereoisomerism
chemical_list: D001688:Biological Products; D006576:Heterocyclic Compounds, 4 or More Rings; D007454:Iodides; D007659:Ketones; D058116:Lewis Acids; D047028:Macrocyclic Compounds; D017616:Magnesium Compounds; C413206:phomactin A; C510205:magnesium iodide