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Diastereo- and chemoselective oxidative monocyclisations of trienes: application of permanganate mediated oxidative cyclisation to the synthesis of Eurylene

Diastereo- and chemoselective oxidative monocyclisations of trienes: application of permanganate mediated oxidative cyclisation to the synthesis of Eurylene
Diastereo- and chemoselective oxidative monocyclisations of trienes: application of permanganate mediated oxidative cyclisation to the synthesis of Eurylene
A formal synthesis of eurylene (1.1) has been achieved where both trans- and cis-THF fragments were synthesised using diastereo- and chemoselective oxidative monocyclisations of triene systems. Synthesis of the trans-THF aldehyde fragment 1.50 of eurylene was accomplished starting from nerol, using (+)-trans tritylcyclohexanol (TTC) as a chiral auxiliary to direct the stereosfacial selectivity during the oxidative cyclisation of 1,5,9-triene 1.185 by sodium permanganate. The oxidative cyclisation used the new chiral auxiliary (TTC) as a highly effective chiral controller for the formation of the 2,5-substituted THF diol product with high diastereoselectivity (dr ?13:1). Synthesis of cis-THF right hand fragment 1.189 was also achieved using permanganate mediated oxidative cyclisation of a 1,5,9-triene 1.60. The diastereoselectivity of the oxidation was controlled by using (2S)-10,2 camphorsultam as a chiral auxiliary. Consequently, seven, out of eight, stereogenic centres of eurylene were established by stereoselective permanganate oxidative cyclisations of 1,5,9-trienes. Towards the completion of the total synthesis of eurylene a chiral sulfoxide strategy was investigated to establish the eighth stereogenic centre and couple the two fragments. In addition a hydroxylsulfone dianion coupling strategy was also investigated. The stereochemical correlation for oxidative cyclisation products from trans-cumylcyclohexanol (TCC) and trans-tritylcyclohexanol (TTC) diene and triene esters was achieved. The oxidative cyclisation products were converted to a common intermediate and analysed by chiral HPLC to confirm absolute configuration. NOESY and NOE NMR studies were applied to some of 2 substituted cyclohexyl dienoates and an oxidative cyclisation product to study their conformation in solution.
Mohammed, Azzam
c0348c6f-0911-457b-8a04-ff568591941e
Mohammed, Azzam
c0348c6f-0911-457b-8a04-ff568591941e
Brown, Richard
21ce697a-7c3a-480e-919f-429a3d8550f5

(2015) Diastereo- and chemoselective oxidative monocyclisations of trienes: application of permanganate mediated oxidative cyclisation to the synthesis of Eurylene. University of Southampton, Chemistry, Doctoral Thesis, 181pp.

Record type: Thesis (Doctoral)

Abstract

A formal synthesis of eurylene (1.1) has been achieved where both trans- and cis-THF fragments were synthesised using diastereo- and chemoselective oxidative monocyclisations of triene systems. Synthesis of the trans-THF aldehyde fragment 1.50 of eurylene was accomplished starting from nerol, using (+)-trans tritylcyclohexanol (TTC) as a chiral auxiliary to direct the stereosfacial selectivity during the oxidative cyclisation of 1,5,9-triene 1.185 by sodium permanganate. The oxidative cyclisation used the new chiral auxiliary (TTC) as a highly effective chiral controller for the formation of the 2,5-substituted THF diol product with high diastereoselectivity (dr ?13:1). Synthesis of cis-THF right hand fragment 1.189 was also achieved using permanganate mediated oxidative cyclisation of a 1,5,9-triene 1.60. The diastereoselectivity of the oxidation was controlled by using (2S)-10,2 camphorsultam as a chiral auxiliary. Consequently, seven, out of eight, stereogenic centres of eurylene were established by stereoselective permanganate oxidative cyclisations of 1,5,9-trienes. Towards the completion of the total synthesis of eurylene a chiral sulfoxide strategy was investigated to establish the eighth stereogenic centre and couple the two fragments. In addition a hydroxylsulfone dianion coupling strategy was also investigated. The stereochemical correlation for oxidative cyclisation products from trans-cumylcyclohexanol (TCC) and trans-tritylcyclohexanol (TTC) diene and triene esters was achieved. The oxidative cyclisation products were converted to a common intermediate and analysed by chiral HPLC to confirm absolute configuration. NOESY and NOE NMR studies were applied to some of 2 substituted cyclohexyl dienoates and an oxidative cyclisation product to study their conformation in solution.

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Published date: 19 October 2015
Organisations: University of Southampton, Chemistry

Identifiers

Local EPrints ID: 384993
URI: http://eprints.soton.ac.uk/id/eprint/384993
PURE UUID: 3e73c883-2203-4b01-ae63-ad9878b11483
ORCID for Richard Brown: ORCID iD orcid.org/0000-0003-0156-7087

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Date deposited: 18 Dec 2015 14:04
Last modified: 19 Oct 2018 04:01

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