Phosphinic acids: Synthesis, acidity measurements and their application in asymmetric catalysis

Griffiths, Emily Faye (2025) Phosphinic acids: Synthesis, acidity measurements and their application in asymmetric catalysis. Doctoral thesis (PhD), Manchester Metropolitan University.

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Abstract

Brønsted acids, such as phosphoric acids derived from chiral 1,1’-bi-2-naphthol (BINOL), are important catalysts, particularly in the formation of new carboncarbon bonds and chiral centres. The asymmetric catalytic capabilities of these Brønsted acids are closely related to their structure and acidity. The synthetic routes towards this class of organophosphorous catalysts consist of low-yielding excessive steps, often using reagents with negative environmental impacts. A novel route towards new BINOL-derived phosphorous Brønsted acids is reported, circumventing three steps with low atom economies and the use of restricted reagents. Brønsted phosphinic catalyst (R)-59 was synthesised in yields up to 78% over seven steps. A novel chiral fluorinated ester (R)-57 was synthesised in a yield of 78% over six steps. A 19F{1H} NMR titration experiment was and validated and tailored towards the determination of the pKa value of (rac)- 59, which was calculated to be in the range of 8.47-8.71. Three sulfonamide compounds were synthesised as references during the 19F{1H} NMR titration and novel crystallographic data of their coordinated sodium complexes are reported. A library of Brønsted acid catalysts, inclusive of the novel ester (R)-57, were screened in an asymmetric Friedel-Crafts reaction to enable direct comparisons of the effect of fluorinating BINOL-based phosphinic atropisomers at the α-position to the phosphorous atom on their catalytic ability.