title: Total synthesis of the congested propellane alkaloid (-)-acutumine.
abstract: The enantioselective total synthesis of (-)-acutumine is described. The synthetic strategy was inspired by the premise that the cyclohexenone ring could be derived from an aromatic precursor. After successful construction of a propellane model system, an initial attempt to prepare the spirocyclic subunit was thwarted by incorrect regioselectivity in a radical cyclization. A second-generation approach involving a radical-polar crossover reaction was successful, and the chemistry developed in the aforementioned model system was then applied to synthesize the natural product. Key reactions included a phenolic oxidation, a diastereoselective ketone allylation utilizing Nakamura's chiral allylzinc reagent, an anionic oxy-Cope rearrangement, an acid-promoted cyclization of a secondary amine onto an α,β-unsaturated ketal, and a regioselective methyl enol etherification of a 1,3-diketone.
authors.affiliation: Department of Chemistry and Biochemistry, Brigham Young University, Provo, Utah, 84602, USA. scastle@chem.byu.edu.
authors.forename: Steven L
authors.initials: SL
authors.lastname: Castle
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D000498:Allyl Compounds / Q000737:chemistry; D001688:Biological Products / Q000138:chemical synthesis* / Q000737:chemistry; D003500:Cyclization; D007659:Ketones / Q000737:chemistry; D032841:Sinomenium / Q000737:chemistry*; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D000470:Alkaloids; D000498:Allyl Compounds; D001688:Biological Products; D007659:Ketones; D013141:Spiro Compounds; C442344:acutumine
keywords: anionic oxy-Cope rearrangements; asymmetric ketone allylations; natural products; radical-polar crossover reactions; total synthesis