The Application of sSPhos as a Chiral Ligand in Palladium-Catalysed Reactions: Arylative Dearomatisations, and Heteroarylative Cyclisations with Alkenes
Pd(0)-catalysed arylative dearomatisation of phenols generates complex stereocentre-containing products from simple planar phenols. The first half of this thesis will summarise our efforts to develop general enantioselective variants of these methods. The second half of this thesis focuses on the development of enantioselective heteroarylative cyclisations with alkenes. Central to all our results is the use of a sulfonated chiral ligand, sSPhos. This ligand was first reported in 2005 by Anderson and Buchwald for performing cross-coupling reactions in water. It was repurposed by the Phipps group, first to control site-selectivity in cross-coupling reactions, and then to control enantioselectivity in atroposelective Suzuki-Miyaura couplings. The work described in this thesis extends its use as a chiral ligand to new reaction types. In all cases, enantioinduction is thought to arise from the involvement of the ligand sulfonate group in attractive substrate-ligand ionic interactions. The first results chapter will discuss the application of the Pd/sSPhos catalytic system in enantioselective intramolecular arylative dearomatisations of phenols. This work was conducted in collaboration with a former postdoc in the Phipps group, Dr David Whalley, and most of the results were published in 2023 (J. Am. Chem. Soc. 2023, 145, 47, 25553–25558). The second results chapter will present the extension of this concept to an intermolecular arylative dearomatisation reaction, with selected results published in 2024 (J. Am. Chem. Soc. 2024, 146, 34970-34978). The third chapter discusses unpublished results on the application of the same catalytic system to the cyclisation of 2-allylanilines and 2-allylphenols with aryl bromide electrophiles, for the synthesis of chiral indolines and 2,3-dihydrobenzofurans. This project is ongoing and being continued by Paul Jirsch, a visiting Master’s student in the Phipps group. The final chapter presents an enantioselective formal synthesis of a natural product, (–)-aflatoxin B2. The key step was a highly enantioselective carboetherification catalysed by Pd/sSPhos. Selected results were published earlier this year (Org. Lett. 2025, 27, 8344-8348).
palladium, catalysis, asymmetric, dearomatisation
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