title: Polyhydroxylated pyrrolizidine alkaloids from transannular iodoaminations: application to the asymmetric syntheses of (-)-hyacinthacine A1, (-)-7a-epi-hyacinthacine A1, (-)-hyacinthacine A2, and (-)-1-epi-alexine.
abstract: The transannular iodoamination of substituted 1,2,3,4,7,8-hexahydroazocine scaffolds has been developed into a versatile, diastereodivergent route to enable the synthesis of a range of pyrrolizidine alkaloids, as demonstrated by the syntheses of (-)-hyacinthacine A1, (-)-7a-epi-hyacinthacine A1, (-)-hyacinthacine A2, and (-)-1-epi-alexine. The requisite 1,2,3,4,7,8-hexahydroazocines (bearing either an N-α-methyl-p-methoxybenzyl group or no N-substituent) were readily prepared via conjugate addition of lithium (R)-N-but-3-enyl-N-(α-methyl-p-methoxybenzyl)amide to either tert-butyl (4S,5R,E)-4,5-dihydroxy-4,5-O-isopropylidene-2,7-dienoate (derived from d-ribose) or tert-butyl (S,S,E)-4,5-dihydroxy-4,5-O-isopropylidene-2,7-dienoate (derived from l-tartaric acid) coupled with in situ enolate oxidation with (-)-camphorsulfonyloxaziridine, followed by ring-closing metathesis with Grubbs I catalyst. Subsequent reaction with I2 resulted in transannular iodoamination (accompanied by concomitant loss of the N-α-methyl-p-methoxybenzyl group for tertiary amine substrates) to give the corresponding pyrrolizidine scaffolds.
authors.affiliation: Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford OX1 3TA, UK.
authors.forename: E Anne
authors.initials: EA
authors.lastname: Brock
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Davies
authors.forename: James A
authors.initials: JA
authors.lastname: Lee
authors.forename: Paul M
authors.initials: PM
authors.lastname: Roberts
authors.forename: James E
authors.initials: JE
authors.lastname: Thomson
mesh_terms: D000586:Amination; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D008968:Molecular Conformation; D011763:Pyrrolizidine Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: C584192:1-epi-alexine; C584191:7a-epi-hyacinthacine A1; D011763:Pyrrolizidine Alkaloids; C508850:hyacinthacine A1; C500284:hyacinthacine A2