Issue 19, 2013

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.

Graphical abstract: Polyhydroxylated pyrrolizidine alkaloids from transannular iodoaminations: application to the asymmetric syntheses of (−)-hyacinthacine A1, (−)-7a-epi-hyacinthacine A1, (−)-hyacinthacine A2, and (−)-1-epi-alexine

Supplementary files

Article information

Article type
Paper
Submitted
30 1 2013
Accepted
14 3 2013
First published
14 3 2013

Org. Biomol. Chem., 2013,11, 3187-3202

Polyhydroxylated pyrrolizidine alkaloids from transannular iodoaminations: application to the asymmetric syntheses of (−)-hyacinthacine A1, (−)-7a-epi-hyacinthacine A1, (−)-hyacinthacine A2, and (−)-1-epi-alexine

E. A. Brock, S. G. Davies, J. A. Lee, P. M. Roberts and J. E. Thomson, Org. Biomol. Chem., 2013, 11, 3187 DOI: 10.1039/C3OB40205C

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