There is a coherence that connects the diverse topics that we have worked on, in that one project led logically to another. Thus our early studies on mechanisms of H exchange in amides (1) led to H exchange in amidines, to the stereochemistry of imidate anions (2), to the role of hydrogen-bonding, and to NMR methods for chemical kinetics, including 2D-EXSY spectroscopy. Another connection was an OH–-catalyzed NH exchange in amines (3), which had been proposed to support the hypothesis of stereoelectronic control. We therefore questioned that hypothesis and analyzed it critically, tested it, and found counterexamples and an alternative hypothesis. The thermodynamic counterpart to stereoelectronic control is the anomeric effect, so we next addressed the lower one-bond NMR coupling constants in ethers ("Perlin effect") and also the reverse anomeric effect (4), which we could reject. The latter studies required development of a highly accurate NMR titration method that we could use to measure the additional steric bulk resulting from protonation of a substituent, and we could document an unusually strong dependence of conformation on solvent (5). The NMR titration method is also applicable to measuring secondary isotope effects on acidity, and we could demonstrate (6) that they arise from n-σ* delocalization and changes of zero-point energy, not from an inductive effect. These results are supported by DFT calculations that demonstrate the stereoelectronic nature of the interaction. Other studies of isotope effects included the kinetic isotope effect for both dissociation and H exchange of aqueous NH4+ and for C-N rotation in amides (7). The role of hydrogen-bonding in proton exchange led us to study the rotation of NH4+ within its solvent cage and then to the question of the symmetry of hydrogen bonds in solution (8 vs 9). All of these projects, as well as other unrelated ones involving malonic anhydride or nucleophilic addition to p-benzyne diradicals or hydronation of a naked aryl anion, have raised and answered fundamental questions that have been enjoyable to address.

Award Address (James Flack Norris Award in Physical Organic Chemistry sponsored by the ACS Northeastern Section). Logic behind a physical-organic chemist's research topics

249th National Meeting (2015)

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