title: Total synthesis of (±)-rocaglamide via oxidation-initiated Nazarov cyclization.
abstract: This article describes the evolution of a Nazarov cyclization-based synthetic strategy targeting the anticancer, antiinflammatory, and insecticidal natural product (±)-rocaglamide. Initial pursuit of a polarized heteroaromatic Nazarov cyclization to construct the congested cyclopentane core revealed an unanticipated electronic bias in the pentadienyl cation. This reactivity was harnessed in a successful second-generation approach using an oxidation-initiated Nazarov cyclization of a heteroaryl alkoxyallene. Full details of these two approaches are given, as well as the characterization of undesired reaction pathways available to the Nazarov cyclization product. A sequence of experiments that led to an understanding of the unexpected reactivity of this key intermediate is described, which culminated in the successful total synthesis of (+)-rocaglamide.
authors.affiliation: Department of Chemistry, University of Rochester, Rochester, New York 14627, USA.
authors.forename: John A
authors.initials: JA
authors.lastname: Malona
authors.forename: Kevin
authors.initials: K
authors.lastname: Cariou
authors.forename: William T
authors.initials: WT
authors.lastname: Spencer
authors.forename: Alison J
authors.initials: AJ
authors.lastname: Frontier
mesh_terms: D000466:Alkadienes / Q000737:chemistry*; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis; D001572:Benzofurans / Q000138:chemical synthesis* / Q000737:chemistry; D003500:Cyclization; D003517:Cyclopentanes / Q000737:chemistry*; D007306:Insecticides / Q000138:chemical synthesis; D007659:Ketones / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010084:Oxidation-Reduction; D013237:Stereoisomerism
chemical_list: D000466:Alkadienes; D000893:Anti-Inflammatory Agents; D000972:Antineoplastic Agents, Phytogenic; D001572:Benzofurans; D003517:Cyclopentanes; D007306:Insecticides; D007659:Ketones; C107772:rocaglamide