Stereoelectronic Effects in General Base Catalysis by Carboxylate. Theoretical Calculations and Studies in the Synthesis of New Intramolecular Models of Enzymatic Catalysis.
Date of Award
Doctor of Philosophy (PhD)
The hypothesis of the existence of stereoelectronic effects in the reactions in which carboxylate acts as a general base catalyst is further studied through the use of theoretical methods. Ab initio calculations on the structures and relative energies of the syn and anti conformations of formic acid at different degrees of solvation are described. These calculations indicate that the syn conformation is more stable in aqueous phase than the anti by 11.9 (at the STO-3G//STO-3G level), 6.9 (4-31G//4-31G), and 2.5 kcal/mol (6-31G(,**)//4-31G). This last number, though, comes from single point calculations at the 6-31G(,**) level on the 4-31G optimized structure and is not consistent with the trends observed with other basis sets. The greater stability of the syn conformation of carboxylic acids in aqueous solution should cause the higher basicity of carboxylate ion when acting as a base in the syn orientation. In order to experimentally test this hypothesis, an intramolecular model of ester hydrolysis reactions with a syn-oriented carboxylate is designed and progress towards its synthesis is described. To test the more critical reactions in the synthetic scheme, a series of stilbene-containing cyclic ethers is synthesized through the use of a novel etherification procedure in mixed solvents in very high yields, followed by a low-valent titanium induced coupling of bis(carbonyl) compounds. Overall yields of 61 to 74% for the two-step conversions are obtained. The crystal structures by X-ray diffraction of some of these new compounds are determined and described. To extend the synthetic sequence described above to functionalized stilbenes, a large number of 2,6-disubstituted benzaldehydes with various protecting groups are prepared and their selective deprotections investigated. Several bis(aryl) ethers are prepared using the etherification reaction used for the cyclic stilbenes and transformed into bis(benzaldehyde) compounds containing protected functional groups by dilithiation, followed by reaction with N,N-dimethylformamide. All attempts to form stilbenes from these compounds by reaction with low-valent titanium result in decomposition. Alternative preparations, both short and highly probable, of the desired models from the intermediates already synthesized are suggested.
Tirado-rives, Julian, "Stereoelectronic Effects in General Base Catalysis by Carboxylate. Theoretical Calculations and Studies in the Synthesis of New Intramolecular Models of Enzymatic Catalysis." (1984). LSU Historical Dissertations and Theses. 4032.