Ortho-Aminomethylphenylboronic acids and ortho-Iminophenylboronic acids : structural and optical studies and synthetic applications

The tools and principles of physical organic chemistry have spread far and wide to many subdisciplines of organic chemistry. Chapter 1 highlights examples of physical organic chemistry being applied to studies in other arenas and details its role in this dissertation. In 1994, Shinkai reported a saccharide sensor composed of a phenylboronic acid with a pendant anthracene. “Shinkai’s Host” becomes significantly more fluorescent in the presence of saccharides, but the mechanism for this turn-on has been debated. Previous work established how binding occurs, and Chapter 2 elucidates the mechanism of fluorescence turn-on. The experiments presented show that the fluorescence modulation is largely a function of disaggregation of the fluorophore, and that binding to a saccharide does not influence the intensity of fluorescence. In other words, binding and fluorescence turn-on both occur in the presence of saccharides, but these two phenomena are only correlated; there is no causal link between the two. Bull and James have developed a three-component assembly consisting of 2-formylphenylboronic acid, a diol, and a primary amine. The primary amine condenses onto the formyl group to form an imine, while the diol condenses onto the boronic acid to form a cyclic boronate ester. The nitrogen and boron atoms have several possibilities for interaction, depending on the solvent. In Chapter 3, structural studies are carried out on this three-component assembly in order to assign the type of N-B interaction in protic and aprotic solvent. Further, the complex equilibrium between the three components is investigated in detail, and individual binding constants are calculated. Chapter 4 explores the Bull-James assembly in two additional contexts. In the first, a procedure is developed for use in an undergraduate teaching laboratory. In the second, the assembly is used simultaneously as a chiral auxiliary and an in situ enantiomeric excess determination platform for the kinetic resolution of a chiral primary amine alkyne via a copper-catalyzed azide-alkyne cycloaddition (CuAAC). Chapter 5 details three mechanistic approaches to the reversibility of CuAAC. Though none of the approaches comes to fruition, this chapter brings the dissertation full circle, with much of the design of the experiments rooted in physical organic chemistry.