The University of Southampton
University of Southampton Institutional Repository

Oxidative cyclisation of 1,5-dienes by matel oxo agents: synthetic and computational investigations

Oxidative cyclisation of 1,5-dienes by matel oxo agents: synthetic and computational investigations
Oxidative cyclisation of 1,5-dienes by matel oxo agents: synthetic and computational investigations
2,5-dihydroxyalkyl substituted tetrahydrofurans (THF-diols) are present in many natural and synthetic products. An efficient approach to THF-diols involves oxidative cyclisation of 1,5-dienes mediated by permanganate ion. The permanganate-promoted oxidative cyclisation of 2-methylenehex-5-enoic acid bearing different aromatic esters was investigated with chiral phase transfer catalyst (CPTC), realising excellent ee’s and yields for the first time as a direct approach. No asymmetric induction was obstained in the absence of aromatic ester group in substrates. Two functional groups, α-naphthyl and 2,3-dichlorophenyl, displayed ee’s in the range of 90%-97%, indicating that the high ee’s can be achieved through a combination of steric and electronic effects where the optimised aryl ester group may achieve a π-stacking interaction with the CPTC. Moderate ee’s were achieved for the majority of aromatic ester substitutions with electron-withdrawing or electron-donating groups, with the exception of the 2,3-dichlorophenyl ester. Enantioinduction was decreased when the electron-rich alkene was substituted with a trans-phenyl group. The CPTC oxidative cyclisation of a 1,5,9-trienoate containing the α-naphthyl group showed a moderate ee and yield.

The reaction mechanism of THF-diol formation from permanganate-mediated and osmium-promoted oxidative cyclisation of 1,5-dienes was studied using high-level DFT simulations ((SMD)-M062X/aug-cc-pVDZ/ECP), showing good agreement with experimental observations, and led to an understanding the key role of acid in promoting the cyclisation step. Ligand exchange with sigma donors such as water and NMO was shown for the FRS intermediate Os(VI) and Mn(V) glycolates. Cyclisation of the protonated Os(VI) dioxoglycolate and Mn(V) glycolate was found to be kinetically and thermodynamically favoured in comparison to other pathways such as reoxidation (Os(VI)Os(VIII) or Mn(V)→Mn(VI)). Although reoxidation of Mn(V)→Mn(VI) was calculated to be disfavoured, decomposition to carbonyl compounds and Mn(IV) was found to be the favoured pathway rather than cyclisation if reoxidation takes place. However, in the absence of acid,
reoxidation of Os(VI)→Os(VIII) was found to be favoured and stimulated a second cycle pathway over cyclisation, as observed experimentally.

Additional insight into the contributory factors was provided by FMO and distortion/interaction energy analysis, in which increasing electrophilicity of the protonated intermediates Os(VI) and Mn(V) glycolates leads to favorable TS interaction energy and attenuated distortion of the tetrahedral Os(VI) and Mn(V) glycolates to deliver the favoured TS’s. An asynchronous (3+2) addition of the O—M—O species, M = Os or Mn, across the alkene double bond with faster development of the C—O[M] bonds compared to C—O[THF] bonds, was obtained by molecular dynamics simulations performed on the SRS. Releasing THF-diol from Mn(III) THF-diolate was found to accessed via acidic disproportionation, whereas for the Os-catalysed reaction, reoxidation of Os(IV) THF-diolate was required to release THF-diol and an Os(VIII) species to complete the catalytic cycle.
Universty of Southampton
Hussein, Aqeel Alaa
c6645ce9-c288-4b21-8af4-6f481b600bf1
Hussein, Aqeel Alaa
c6645ce9-c288-4b21-8af4-6f481b600bf1
Brown, Richard C.D.
21ce697a-7c3a-480e-919f-429a3d8550f5

Hussein, Aqeel Alaa (2018) Oxidative cyclisation of 1,5-dienes by matel oxo agents: synthetic and computational investigations. University of Southampton, Doctoral Thesis, 441pp.

Record type: Thesis (Doctoral)

Abstract

2,5-dihydroxyalkyl substituted tetrahydrofurans (THF-diols) are present in many natural and synthetic products. An efficient approach to THF-diols involves oxidative cyclisation of 1,5-dienes mediated by permanganate ion. The permanganate-promoted oxidative cyclisation of 2-methylenehex-5-enoic acid bearing different aromatic esters was investigated with chiral phase transfer catalyst (CPTC), realising excellent ee’s and yields for the first time as a direct approach. No asymmetric induction was obstained in the absence of aromatic ester group in substrates. Two functional groups, α-naphthyl and 2,3-dichlorophenyl, displayed ee’s in the range of 90%-97%, indicating that the high ee’s can be achieved through a combination of steric and electronic effects where the optimised aryl ester group may achieve a π-stacking interaction with the CPTC. Moderate ee’s were achieved for the majority of aromatic ester substitutions with electron-withdrawing or electron-donating groups, with the exception of the 2,3-dichlorophenyl ester. Enantioinduction was decreased when the electron-rich alkene was substituted with a trans-phenyl group. The CPTC oxidative cyclisation of a 1,5,9-trienoate containing the α-naphthyl group showed a moderate ee and yield.

The reaction mechanism of THF-diol formation from permanganate-mediated and osmium-promoted oxidative cyclisation of 1,5-dienes was studied using high-level DFT simulations ((SMD)-M062X/aug-cc-pVDZ/ECP), showing good agreement with experimental observations, and led to an understanding the key role of acid in promoting the cyclisation step. Ligand exchange with sigma donors such as water and NMO was shown for the FRS intermediate Os(VI) and Mn(V) glycolates. Cyclisation of the protonated Os(VI) dioxoglycolate and Mn(V) glycolate was found to be kinetically and thermodynamically favoured in comparison to other pathways such as reoxidation (Os(VI)Os(VIII) or Mn(V)→Mn(VI)). Although reoxidation of Mn(V)→Mn(VI) was calculated to be disfavoured, decomposition to carbonyl compounds and Mn(IV) was found to be the favoured pathway rather than cyclisation if reoxidation takes place. However, in the absence of acid,
reoxidation of Os(VI)→Os(VIII) was found to be favoured and stimulated a second cycle pathway over cyclisation, as observed experimentally.

Additional insight into the contributory factors was provided by FMO and distortion/interaction energy analysis, in which increasing electrophilicity of the protonated intermediates Os(VI) and Mn(V) glycolates leads to favorable TS interaction energy and attenuated distortion of the tetrahedral Os(VI) and Mn(V) glycolates to deliver the favoured TS’s. An asynchronous (3+2) addition of the O—M—O species, M = Os or Mn, across the alkene double bond with faster development of the C—O[M] bonds compared to C—O[THF] bonds, was obtained by molecular dynamics simulations performed on the SRS. Releasing THF-diol from Mn(III) THF-diolate was found to accessed via acidic disproportionation, whereas for the Os-catalysed reaction, reoxidation of Os(IV) THF-diolate was required to release THF-diol and an Os(VIII) species to complete the catalytic cycle.

Text
Aqeel Alaa Hussein Thesis - Version of Record
Available under License University of Southampton Thesis Licence.
Download (16MB)

More information

Published date: December 2018

Identifiers

Local EPrints ID: 428051
URI: http://eprints.soton.ac.uk/id/eprint/428051
PURE UUID: 4c3006d4-6928-4ca9-842a-42309ed6d185
ORCID for Richard C.D. Brown: ORCID iD orcid.org/0000-0003-0156-7087

Catalogue record

Date deposited: 07 Feb 2019 17:30
Last modified: 31 Jan 2020 05:01

Export record

Contributors

Author: Aqeel Alaa Hussein
Thesis advisor: Richard C.D. Brown ORCID iD

University divisions

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

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×