Determination of the <i>pK</i> _<i>a</i> Value of a Brønsted Acid by ¹⁹ F NMR Spectroscopy

Brønsted acids, such as phosphoric acids derived from chiral 1,1'-bi-2-naphthol (BINOL), are important catalysts in the formation of carbon-carbon and carbon-heteroatom bonds, for example. The catalytic activity of these Brønsted acids is strongly linked to their acidity, and as such, the evaluation of compounds to determine pK_a values provides insight into their catalytic activity. Herein, a ¹⁹F{¹H} NMR methodology is detailed to determine the pK_a of a fluorinated binaphthyl-derived phosphinic acid, rac-1, in acetonitrile and in the presence of a fluorinated sulfonamide reference compound (2-4). The approach was tested initially using 2 and 3, with the ΔpK_a (0.08) in strong agreement with previously reported values (6.6 for 2 and 6.68/6.73 for 3). Sigmoidal curves of normalised chemical shift change (Δδ) against equivalents of the base phosphazene P₁-^tBu added overlapped for 2 and 3, but in the case of rac-1 and either 2, 3 or 4, there was significant separation. A variety of different approaches for determining the ΔpK_a were compared. Values of pK_a determined when the normalised Δδ was 90% were optimal for 2 and 3, whereas a normalised Δδ of 75% was optimal for 4, resulting in the pK_a of rac-1 being determined to be 8.47-8.71.