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

Hung V Pham; David B. C Martin; Christopher D Vanderwal; K. N Houk

doi:10.1039/C2SC01072K

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

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

Hung V Pham, David B. C Martin, Christopher D Vanderwal and K. N Houk

Chemical science (Cambridge), Vol.2012(3), pp.1650-1655

2012

DOI: 10.1039/C2SC01072K

PMCID: PMC3354770

PMID: 22611483

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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.

Details

Title: Subtitle: The Intramolecular Diels–Alder Reaction of Tryptamine-Derived Zincke Aldehydes Is a Stepwise Process
Creators: Hung V Pham - Department of Chemistry and Biochemistry, University of California, Los Angeles, 607 Charles E. Young Drive, Los Angeles, California 90095-1569
David B. C Martin - 1102 Natural Sciences II, Department of Chemistry, University of California, Irvine, California 92697-2025
Christopher D Vanderwal - 1102 Natural Sciences II, Department of Chemistry, University of California, Irvine, California 92697-2025
K. N Houk - Department of Chemistry and Biochemistry, University of California, Los Angeles, 607 Charles E. Young Drive, Los Angeles, California 90095-1569
Resource Type: Journal article
Publication Details: Chemical science (Cambridge), Vol.2012(3), pp.1650-1655
DOI: 10.1039/C2SC01072K
PMID: 22611483
PMCID: PMC3354770
NLM abbreviation: Chem Sci
ISSN: 2041-6520
eISSN: 2041-6539
Grant note: R01 GM036700-27 || GM / National Institute of General Medical Sciences : NIGMS
Language: English
Date published: 2012
Academic Unit: Iowa Neuroscience Institute; Chemistry
Record Identifier: 9984065751502771

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