title: Efficient entry to the [2.2.2]-diazabicyclic ring system via diastereoselective domino reaction sequence.
abstract: A domino reaction sequence involving aldol condensation, alkene isomerization, and intramolecular hetero-Diels-Alder cycloaddition for the synthesis of [2.2.2]-diazabicyclic structures is reported. Excellent diastereofacial control during the cycloaddition is enforced with a removable chiral phenyl aminal diketopiperazine substituent. The reaction sequence rapidly generates molecular complexity and is competent with both enolizable and nonenolizable aldehyde substrates (nine examples total). Progress toward the synthesis of malbrancheamide B, a protypical member of the [2.2.2]-diazabicyclic natural product family, is also disclosed.
authors.affiliation: Department of Chemistry, The College of William & Mary , P.O. Box 8795, Williamsburg, Virginia 23187, United States.
authors.forename: Kaila A
authors.initials: KA
authors.lastname: Margrey
authors.forename: Alex J
authors.initials: AJ
authors.lastname: Chinn
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Laws
authors.forename: Robert D
authors.initials: RD
authors.lastname: Pike
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Scheerer
mesh_terms: D000447:Aldehydes / Q000737:chemistry; D000475:Alkenes / Q000737:chemistry*; D001688:Biological Products / Q000138:chemical synthesis* / Q000737:chemistry; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis / Q000737:chemistry*; D061565:Cycloaddition Reaction; D026121:Indole Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D013237:Stereoisomerism
chemical_list: D000447:Aldehydes; D000475:Alkenes; D001688:Biological Products; D019086:Bridged Bicyclo Compounds, Heterocyclic; D026121:Indole Alkaloids; C530842:malbrancheamide B; C116609:3-hydroxybutanal