Concise, stereodivergent and highly stereoselective synthesis of cis- and trans-2-substituted 3-hydroxy-piperidines - development of a phosphite-driven cyclodehydration

Peter H. Huy, Julia C. Westphal, Ari M.P. Koskinen

    Research output: Contribution to journalArticleScientificpeer-review

    16 Citations (Scopus)
    172 Downloads (Pure)

    Abstract

    A concise (5 to 6 steps), stereodivergent, highly diastereoselective (dr up to >19:1 for both stereoisomers) and scalable synthesis (up to 14 g) of cis- and trans-2-substituted 3-piperidinols, a core motif in numerous bioactive compounds, is presented. This sequence allowed an efficient synthesis of the NK-1 inhibitor L-733,060 in 8 steps. Additionally, a cyclodehydration-realizing simple triethylphosphite as a substitute for triphenylphosphine is developed. Here the stoichiometric oxidized P(V)-byproduct (triethylphosphate) is easily removed during the work up through saponification overcoming separation difficulties usually associated to triphenylphosphine oxide.
    Original languageEnglish
    Pages (from-to)369-383
    JournalBeilstein Journal of Organic Chemistry
    Volume10
    Issue number10
    DOIs
    Publication statusPublished - 2014
    MoE publication typeA1 Journal article-refereed

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