Asymmetric addition reactions using chiral diamine derived catalysts

Davison, Christopher (2015) Asymmetric addition reactions using chiral diamine derived catalysts. PhD thesis, University of Nottingham.

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Abstract

This thesis details the use of chiral diamine derived catalysts in asymmetric addition reactions. Three separate projects are outlined within.

The first project involved the investigation of dibenz[c,e]azepinium salt 113 as a catalyst for the aldol reaction. The catalyst was synthesised in 4 steps from commercially available 1R,2R-diaminocyclohexane in 74% overall yield. It was found to be an efficient catalyst in the aldol reaction of cyclic ketones with a range of aromatic aldehydes, giving high yields, diastereo- and enantioselectivities. This catalyst was also found to be effective when acyclic ketones were used, in which case the major diastereoisomer produced was no longer an anti-aldol but a the syn-aldol. A catalytic cycle for these reactions is proposed, with the stereochemical outcome of these reactions being further investigated by computational calculations.

The second project investigated the use of chiral primary amine catalysts in the conjugate addition of N-heterocycles to α,β-unsaturated ketones. It was found that commercially available 1R,2R-diaminocyclohexane 114 was an efficient and enantioselective catalyst for the addition of pyrazoles to α,β-unsaturated ketones. Through comparison with the performance of related catalyst structures we propose a catalytic cycle in which 114 forms bonds with both the α,β-unsaturated ketone and the incoming pyrazole. Alternative chiral amines derived from camphor sulfonic acid were investigated as catalysts for the conjugate addition reaction; these proved to be relatively poor catalysts giving the product with a low enantiomeric excess.

Finally, an investigation into intramolecular N-conjugate additions was performed. We found that 9-epi-9-amino-9-deoxyquinine derived squaramide 355 was a highly enantioselective catalyst for the intramolecular cyclisation of sulfonamides to α,β-unsaturated ketones. Best results were seen with α,β-unsaturated ketones conjugated to an aryl group, however squaramide 355 also proved to be an enantioselective catalyst for the cyclisation of methyl ketone and ester conjugated alkenes. In the latter two cases higher temperatures and catalyst loadings were required. In conjunction with molecular modelling studies we propose a catalytic cycle that accounts for the observed stereochemistry.

Item Type: Thesis (University of Nottingham only) (PhD)
Supervisors: Lygo, B.
Denton, R.
Keywords: Asymmetric catalysis, enantioselective N-conjugate addition
Subjects: Q Science > QD Chemistry > QD241 Organic chemistry
Faculties/Schools: UK Campuses > Faculty of Science > School of Chemistry
Item ID: 28682
Depositing User: Davison, Christopher
Date Deposited: 11 Aug 2016 21:47
Last Modified: 13 Sep 2016 19:02
URI: http://eprints.nottingham.ac.uk/id/eprint/28682

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