title: The Intramolecular Diels-Alder Reaction of Tryptamine-Derived Zincke Aldehydes Is a Stepwise Process.
abstract: Computational studies show that the base-mediated intramolecular Diels-Alder of tryptamine-derived Zincke aldehydes, used as a key step in the synthesis of the Strychnos alkaloids norfluorocurarine and strychnine, proceeds via a stepwise pathway. The experimentally determined importance of a potassium counterion in the base is explained by its ability to preorganize the Zincke aldehyde diene in an s-cis conformation suitable to bicyclization. Computation also supports the thermodynamic importance of the generation of a stable enolate in the final reaction step. The thermal cycloreversion reaction of the Diels-Alder products is also found to proceed in a stepwise manner.
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Los Angeles, 607 Charles E. Young Drive, Los Angeles, California 90095-1569.
authors.forename: Hung V
authors.initials: HV
authors.lastname: Pham
authors.forename: David B C
authors.initials: DB
authors.lastname: Martin
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Vanderwal
authors.forename: K N
authors.initials: KN
authors.lastname: Houk