title: The asymmetric syntheses of pyrrolizidines, indolizidines and quinolizidines via two sequential tandem ring-closure/N-debenzylation processes.
abstract: Concise asymmetric syntheses of (-)-lupinine, (+)-isoretronecanol, (+)-5-epi-tashiromine and (R,R)-1-(hydroxymethyl)octahydroindolizine (the azabicyclic core within stellettamides A-C) have been achieved in 8 steps or fewer from commercially available starting materials. The key steps in these syntheses involved the preparation of enantiopure β-amino esters, upon conjugate addition of lithium (R)-N-(p-methoxybenzyl)-N-(α-methyl-p-methoxybenzyl)amide to either ζ-chloro or ζ-hydroxy substituted tert-butyl (E)-hept-2-enoate, or ε-chloro or ε-hydroxy substituted tert-butyl (E)-hex-2-enoate. Activation of the ω-substituent as a leaving group led to SN2-type ring-closure, which occurred with concomitant N-debenzylation via an E1-type deprotection step, to give the corresponding pyrrolidine or piperidine in good yield. Subsequent alkylation of these enantiopure azacycles, followed by a second ring-closure/concomitant N-debenzylation step formed the pyrrolizidine, indolizidine or quinolizidine motif, and reduction with LiAlH4 gave the target compounds in diastereoisomerically and enantiomerically pure form.
authors.affiliation: Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford, OX1 3TA, UK. steve.davies@chem.ox.ac.uk.
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Davies
authors.forename: Ai M
authors.initials: AM
authors.lastname: Fletcher
authors.forename: Emma M
authors.initials: EM
authors.lastname: Foster
authors.forename: Ian T T
authors.initials: IT
authors.lastname: Houlsby
authors.forename: Paul M
authors.initials: PM
authors.lastname: Roberts
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Schofield
authors.forename: James E
authors.initials: JE
authors.lastname: Thomson