Stereoselective synthesis of 2,6- cis -substituted tetrahydropyrans: Brønsted acid-catalyzed intramolecular oxa-conjugate cyclization of α,β-unsaturated ester surrogates

Haruhiko Fuwa, Naoki Ichinokawa, Kenkichi Noto, Makoto Sasaki

    Research output: Contribution to journalArticlepeer-review

    45 Citations (Scopus)

    Abstract

    Intramolecular oxa-conjugate cyclization (IOCC) of α,β- unsaturated carbonyl compounds, triggered by deprotonation with a base, represents a straightforward method for the synthesis of tetrahydropyrans. However, it has been known that stereochemical outcome of IOCC depends on the local structure of substrates and sometimes requires harsh reaction conditions and/or prolonged reaction times for selective formation of 2,6-cis-substituted tetrahydropyrans. These shortcomings limit the feasibility of IOCC in the context of complex natural product synthesis. In this paper, we describe Brønsted acid-catalyzed IOCC of α,β-unsaturated ester surrogates (e.g., α,β-unsaturated thioesters, oxazolidinone imides, and pyrrole amides) under mild reaction conditions, which affords a series of synthetically versatile 2,6-cis-substituted tetrahydropyran derivatives with good to excellent stereoselectivity (dr from 7:1 to >20:1). These α,β-unsaturated carbonyl compounds were found to be more reactive than the corresponding oxoesters that are generally unreactive toward Brønsted acid-catalyzed intramolecular oxa-conjugate additions. The product tetrahydropyrans could be transformed into various derivatives in an efficient manner, highlighting the usefulness of our methodology.

    Original languageEnglish
    Pages (from-to)2588-2607
    Number of pages20
    JournalJournal of Organic Chemistry
    Volume77
    Issue number6
    DOIs
    Publication statusPublished - 2012 Mar 16

    ASJC Scopus subject areas

    • Organic Chemistry

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