I. Studies toward an enantioselective nucleophilic catalyst based on dimethylaminopyridine (DMAP). II. Kinetic study of nucleophilic acylation catalysts

The design of a novel bicyclic 4-dimethylaminopyridine (DMAP) structure, which has an extended network for resonance delocalization is presented. This planar bicyclic structure has been designed so that chiral ligands may be attached to it without resulting in steric deactivation of the nucleophilic pyridine ring nitrogen. Two classes of chiral acylation catalysts based on this core structure have been synthesized.; The first class has a group tethered in a position to act as a face blocking group. This catalyst displayed modest levels of selectivity in the kinetic resolution of aryl alkyl carbinols. The second class of catalysts contain potential face blocking as well as potential side blocking groups. Three variations of a structure which does not have these two groups tethered rigidly into a position to perform the desired blocking functions were synthesized. These catalysts also showed only modest levels of selectivity, however, both classes of catalyst are able to transmit the chiral information contained in the attached ligand to some extent.; An investigation into the kinetics of acylation reactions was undertaken. The activation parameters associated with reactions catalyzed by a representative 2-aryl-2-phosphabicyclo [3.3.0] octane (PBO) catalyst and by the new bicyclic DMAP-derivatives were determined. Based on selectivity data, the dissection of the activation parameters of the reactions into those for the pathways leading to the major and minor enantiomers was accomplished. It was found that the kinetics of these reactions are dominated by entropic factors, effecting both reaction rate and enantioselectivity. The extremely small activation enthalpy for the PBO catalyst (1–2 kcal/mol) results in a mere two fold change in rate over a 60°C temperature range.