The Synthesis and Application of a Chiral Sulfonated Phosphine Ligand to Asymmetric Transition-Metal Catalysis

This thesis describes the synthesis of a chiral sulfonated phosphine ligand, sSPhos, in its enantiopure form and its subsequent application in asymmetric transition-metal catalysis. sSPhos is a dialkylbiaryl phosphine ligand bearing a sulfonate group. This sulfonate group can engage in non-covalent interactions, allowing sSPhos to influence site- and enantioselectivity when employed as a ligand for transition-metal catalysis. The development of a linear chemical resolution route, using (R)-BINOL as a chiral auxiliary, is described. This route allows access to sSPhos in its enantiopure form. The enantiopure sSPhos was then investigated as a chiral ligand in the fields of palladium and gold chemistry. sSPhos was evaluated as a chiral ligand for the Pd-catalysed P-arylation of secondary phosphine oxides. Unfortunately, no enantioselectivity was observed. Furthermore, there were concerns that the secondary phosphine oxides (and their tertiary counterparts which are formed as the product of the reaction) were competitively binding to Pd and displacing sSPhos. sSPhos was then applied as a chiral ligand for a Pd-catalysed atroposelective Suzuki– Miyaura coupling. It was found to be an especially proficient ligand for the formation of 2,2’-biphenols. This is an important scaffold, found in many biologically active compounds and privileged catalyst structures. Excellent enantioselectivities were obtained for a wide range of coupling partners. Mechanistic experiments suggested that sSPhos’ sulfonate group engages in hydrogen bond interactions with the phenolic starting materials, allowing for the high levels of enantioinduction observed. sSPhos was finally tested as a ligand for Au(I) catalysis. Only preliminary studies were performed, but promising enantioselectivity was seen for the [2+2] cycloaddition of alkynes and alkenes. These results highlight sSPhos’ potential as a chiral ligand in the fields of both palladium and gold catalysis.

Name dc:type.qualificationname

Doctor of Philosophy (PhD)

Level dc:type.qualificationlevel

Doctoral

Grantor dc:publisher.institution

University of Cambridge

Year dc:date.issued

2023

Author dc:creator

• Hogenhout, Larissa

Advisor dc:contributor.advisor

• Phipps, Robert

• atroposelectivity
• catalysis
• chemistry
• enantioselectivity
• gold
• palladium
• sSPhos
• Suzuki– Miyaura

Licence

• https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/688d01ad-be70-44fa-a1f1-dc8c7e4ef0df/download
• https://www.rioxx.net/licenses/all-rights-reserved/

Language dc:language

eng

DOI dc:identifier.doi

https://doi.org/10.17863/CAM.111680

OAI identifier oai:identifier

oai:www.repository.cam.ac.uk:1810/373127