The Development of Asymmetric Palladium-Catalysed Transformations Using Chiral Sulfonated Phosphine Ligands

This thesis describes efforts aimed at utilising non-covalent interactions to induce enantioselectivity in palladium-catalysed reactions using sulfonated phosphine ligands. Firstly, a library of achiral sulfonated phosphine ligands that are ion-paired with a chiral cation were synthesised. These ligands only had modest success in a selection of transition metal- catalysed processes evaluated, but encouraging results were obtained for the asymmetric palladium-catalysed allylic alkylation reaction. Next, the thesis details work towards controlling the regioselectivity of the palladium-catalysed π-allyl reactions, by harnessing the directing abilities of the ligand’s anionic sulfonate group. One of the ligands assessed was sSPhos, a commercially-available sulfonated variant of SPhos. Notably, sSPhos possesses axial chirality due to the desymmetrisation of the distal ring upon sulfonation. We were subsequently able to develop a high-yielding and facile procedure to access highly enantioenriched sSPhos via the recrystallisation of its salt with protonated quinidine. The second half of this thesis assesses the efficacy of enantiopure sSPhos in two asymmetric palladium-catalysed reactions: π-allyl nucleophilic additions and atroposelective Suzuki- Miyaura cross-couplings. For asymmetric palladium-catalysed allylic alkylations, high levels of enantioselectivity could be achieved with 1,3-diphenylallyl substrates and nucleophiles possessing one or more electron-withdrawing groups. A large ligand counter-cation was found to be a prerequisite for high levels of enantioselectivity, which was attributed to the cation’s role as a ‘steric shield’ in the enantiodetermining step. Enantiopure sSPhos was next applied in the enantioselective Suzuki-Miyaura cross-couplings to form atropisomeric biaryls with a range of coupling partners. Generally excellent levels of enantioselectivity were observed when both coupling partners contained hydroxy groups ortho to the newly formed biaryl bond, to form 2,2’-biphenols. This was later applied to the double Suzuki-Miyaura cross- coupling to form enantioenriched triphenolic compounds. These promising results demonstrate the considerable potential of chiral sulfonated phosphine ligands in asymmetric palladium-catalysed reactions.

Name dc:type.qualificationname

Doctor of Philosophy (PhD)

Level dc:type.qualificationlevel

Doctoral

Grantor dc:publisher.institution

University of Cambridge

Year dc:date.issued

2022

Author dc:creator

• Docherty, Phil

Advisor dc:contributor.advisor

• Phipps, Robert

• catalysis
• asymmetric
• synthesis
• enantiomers
• palladium
• ligand

Licence

• https://www.rioxx.net/licenses/all-rights-reserved/

Language dc:language

eng

DOI dc:identifier.doi

https://doi.org/10.17863/CAM.92115

OAI identifier oai:identifier

oai:www.repository.cam.ac.uk:1810/344692