title: Concise, stereodivergent and highly stereoselective synthesis of cis- and trans-2-substituted 3-hydroxypiperidines - development of a phosphite-driven cyclodehydration.
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.
authors.affiliation: Aalto University, School of Chemical Technology, Laboratory of Organic Chemistry, Kemistintie 1, 02015 Espoo, Finland.
authors.forename: Peter H
authors.initials: PH
authors.lastname: Huy
authors.affiliation: University of Cologne, Department of Chemistry, Organic Chemistry, Greinstrasse 4, 50939 Cologne, Germany.
authors.forename: Julia C
authors.initials: JC
authors.lastname: Westphal
authors.affiliation: Aalto University, School of Chemical Technology, Laboratory of Organic Chemistry, Kemistintie 1, 02015 Espoo, Finland.
authors.forename: Ari M P
authors.initials: AM
authors.lastname: Koskinen
keywords: amino acids; asymmetric synthesis; cyclodehydration; hydroxypiperidines; natural products; one-pot