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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.

SUBMITTER: Pham HV

PROVIDER: S-EPMC3354770 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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The Intramolecular Diels-Alder Reaction of Tryptamine-Derived Zincke Aldehydes Is a Stepwise Process.

Pham Hung V HV Martin David B C DB Vanderwal Christopher D CD Houk K N KN

Chemical science 20120202 3

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 importanc ...[more]

PMID: 22611483

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