Chiral Proton Catalysis: pK_a Determination for a BAM-HX Brønsted Acid

Abstract

Perrin’s NMR titration procedure has been used to measure the pK_a values for several Brønsted acids. These measurements allow a preliminary determination of the absolute pKa for these chiral acids.

Key words

chiral proton catalysis - pK_a determination - Brønsted acid - NMR titration

References and Notes

• 1 Nugent BM. Yoder RA. Johnston JN. J. Am. Chem. Soc.  2004,  126:  3418 
• 2 Alder RW. Bowman PS. Steele WRS. Winterman DR. J. Chem. Soc., Chem. Commun.  1968,  723 
• 4 Perrin CL. Fabian MA. Anal. Chem.  1996,  68:  2127 
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• 8 Um I.-H. Lee E.-J. Jeon S.-E. J. Phys. Org. Chem.  2002,  15:  561 
• 10 The absolute pK_a measured for pyridinium and picolinium ion are to a single decimal place. The pK_a for pyridinium was determined electrochemically using the perchlorate salt in DMSO. Details for the pK_a measurement for picolinium remain unavailable: Bordwell FG. Acc. Chem. Res.  1988,  21:  456 
• 11 In H₂O, pyridinium (pK_a = 5.23) is less acidic than quinolinium (pK_a = 4.90): Alber A. Goldacre R. Phillips J. J. Chem. Soc.  1948,  2240 
• 12 Charmant JPH. Lloyd-Jones GC. Peakman TM. Woodward RL. Tetrahedron Lett.  1998,  39:  4733 

3

Johnston, J. N.; Yoder, R. A. unpublished work.

9

The level of uncertainty in this value is greater than the others since it requires an estimation of the chemical shift that correlates to 2. In a chart of the movement of ligand chemical shift as a function of titer, there is a clear inflection point at one equivalent of acid relative to the ligand. This strongly suggests that the monosalt can be identified spectroscopically as a single entity, and the calculated differences in pK_a between 2 and 10 is consistent with a >100:1 equilibrium favoring 2. The existence of an inflection point is common in all titrations we have performed to-date in which one would be anticipated.