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

Beilstein Journal of Organic Chemistry

Peter H. Huy¹  Ari M. P. Koskinen¹  Julia C. Westphal² 

[1] Aalto University, School of Chemical Technology, Laboratory of Organic Chemistry, Kemistintie 1, 02015 Espoo, Finland;University of Cologne, Department of Chemistry, Organic Chemistry, Greinstrasse 4, 50939 Cologne, Germany;

关键词: amino acids;    asymmetric synthesis;    cyclodehydration;    hydroxypiperidines;    natural products;    one-pot;   

DOI  :  10.3762/bjoc.10.35

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown