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

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A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä
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Date
2014
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Language
en
Pages
369-383
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BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY, Volume 10, issue 10
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.
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Huy , P H , Westphal , J C & Koskinen , A M P 2014 , ' Concise, stereodivergent and highly stereoselective synthesis of cis- and trans-2-substituted 3-hydroxy-piperidines - development of a phosphite-driven cyclodehydration ' , Beilstein Journal of Organic Chemistry , vol. 10 , no. 10 , pp. 369-383 . https://doi.org/10.3762/bjoc.10.35