Investigations into the synthesis and desymmetrisation of "pseudo"-C2-symmetric compounds
Investigations into the synthesis and desymmetrisation of "pseudo"-C2-symmetric compounds
The synthesis of the ‘pseudo’-C2-symmetric scaffold (3R,4R)-hexahydrofuro[2,3-b]-furan-3,4-diol from L-arabitol is described. The construction of this enantiopure bicycle was achieved via a ‘bufurcating bicyclisation’ of a ‘pseudo’-C2-symmetric acyclic substrate with complete stereocontrol. Two routes were developed, the first utilised a Pd(II) catalysed intramolecular acetalisation while the second an acid catalysed bicyclic acetal formation to achieve the bicyclisation. (3R,4R)-hexahydrofuro[2,3-b]furan-3,4-diol was successfully desymmetrised via selective acylation or silylation of the exo-hydroxyl group using the reagents PivCl, TBDPSCl and TIPSCl. Such desymmetrised compounds would be potential P2 ligands suitable for incorporation into HIV-1 protease inhibitors. During this work, a rare example of a diastereoselective tandem hydroboration/acetal cleavage was encountered, which results in the desymmetrisation of a C2-symmetric alkene. A full discussion and a proposed mechanism are presented.
An attempted formal synthesis of the bis-THF moiety of (+)-Asteltoxin is also described. Although ultimately unsuccessful, this work produced a reliable method for the oxidation of 1,3-diols to 1,3-dialdehydes using the oxidising reagent 2-iodoxybenzoic acid (IBX); a transformation for which few literature precedents exist. Studies into the allylation and α-hydroxyallylation of monoaldehydes and dialdehydes using the reagents of Brown and Roush are also discussed.
Finally, an enantiopure, two-directional approach towards the synthesis of pyrrolizidine bicycles is presented. The synthesis of key 1,3-bis-epoxide intermediate (2R,4R)-3-azido-1,2:4,5-diepoxypentane is described as well as its application to constructing ‘pseudo’-C2-symmetric acyclic molecules via two-directional homologation.
University of Southampton
Jeffery, Martin James
ae2a56e4-7efb-4f3d-b210-c941a815a28b
2005
Jeffery, Martin James
ae2a56e4-7efb-4f3d-b210-c941a815a28b
Jeffery, Martin James
(2005)
Investigations into the synthesis and desymmetrisation of "pseudo"-C2-symmetric compounds.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
The synthesis of the ‘pseudo’-C2-symmetric scaffold (3R,4R)-hexahydrofuro[2,3-b]-furan-3,4-diol from L-arabitol is described. The construction of this enantiopure bicycle was achieved via a ‘bufurcating bicyclisation’ of a ‘pseudo’-C2-symmetric acyclic substrate with complete stereocontrol. Two routes were developed, the first utilised a Pd(II) catalysed intramolecular acetalisation while the second an acid catalysed bicyclic acetal formation to achieve the bicyclisation. (3R,4R)-hexahydrofuro[2,3-b]furan-3,4-diol was successfully desymmetrised via selective acylation or silylation of the exo-hydroxyl group using the reagents PivCl, TBDPSCl and TIPSCl. Such desymmetrised compounds would be potential P2 ligands suitable for incorporation into HIV-1 protease inhibitors. During this work, a rare example of a diastereoselective tandem hydroboration/acetal cleavage was encountered, which results in the desymmetrisation of a C2-symmetric alkene. A full discussion and a proposed mechanism are presented.
An attempted formal synthesis of the bis-THF moiety of (+)-Asteltoxin is also described. Although ultimately unsuccessful, this work produced a reliable method for the oxidation of 1,3-diols to 1,3-dialdehydes using the oxidising reagent 2-iodoxybenzoic acid (IBX); a transformation for which few literature precedents exist. Studies into the allylation and α-hydroxyallylation of monoaldehydes and dialdehydes using the reagents of Brown and Roush are also discussed.
Finally, an enantiopure, two-directional approach towards the synthesis of pyrrolizidine bicycles is presented. The synthesis of key 1,3-bis-epoxide intermediate (2R,4R)-3-azido-1,2:4,5-diepoxypentane is described as well as its application to constructing ‘pseudo’-C2-symmetric acyclic molecules via two-directional homologation.
This record has no associated files available for download.
More information
Published date: 2005
Identifiers
Local EPrints ID: 465679
URI: http://eprints.soton.ac.uk/id/eprint/465679
PURE UUID: 11129c27-739f-4e64-8a53-2ceef3cd3442
Catalogue record
Date deposited: 05 Jul 2022 02:32
Last modified: 23 Jul 2022 02:16
Export record
Contributors
Author:
Martin James Jeffery
Download statistics
Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.
View more statistics