Tandem catalysis in domino olefin cross-metathesis/intramolecular oxa-conjugate cyclization: Concise synthesis of 2,6-cis-substituted tetrahydropyran derivatives

Haruhiko Fuwa, Takuma Noguchi, Kenkichi Noto, Makoto Sasaki

    Research output: Contribution to journalArticlepeer-review

    31 Citations (Scopus)

    Abstract

    Herein, we describe the concise synthesis of 2,6-cis-substituted tetrahydropyran derivatives based on a domino olefin cross-metathesis/ intramolecular oxa-conjugate cyclization (CM/IOCC) reaction. We have found that the domino CM/IOCC of δ-hydroxy olefins with α,β-unsaturated carbonyl compounds (e.g., trans-crotonaldehyde or N-acryloyl-2,5- dimethylpyrrole) could be efficiently achieved in the presence of the second-generation Hoveyda-Grubbs catalyst under elevated temperature conditions, directly affording 2,6-cis-substituted tetrahydropyrans in excellent yields with synthetically useful diastereoselectivity ("auto-tandem catalysis"). In addition, we have found that the domino CM/IOCC of δ-hydroxy olefins with α,β-unsaturated carbonyl compounds could be achieved simply by performing CM in the presence of a Bronsted acid in CH2Cl2 at 25-35 °C, which delivered 2,6-cis-substituted tetrahydropyrans in good yields with excellent diastereoselectivity ("orthogonal-tandem catalysis"). To understand the mechanism of auto-tandem catalysis in the domino CM/IOCC reaction, we have investigated the role of ruthenium hydride complexes in the IOCC of a ζ-hydroxy α,β-unsaturated ketone as a model case.

    Original languageEnglish
    Pages (from-to)8108-8112
    Number of pages5
    JournalOrganic and Biomolecular Chemistry
    Volume10
    Issue number40
    DOIs
    Publication statusPublished - 2012 Oct 28

    ASJC Scopus subject areas

    • Biochemistry
    • Physical and Theoretical Chemistry
    • Organic Chemistry

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