| The main focus of this dissertation was to describe the discovery, development and scope of the hydrogen bonding catalyzed asymmetric Hetero-Diels-Alder (HDA) reaction between 1-amino-3-siloxybutadienes and unactivated aldehydes. The alpha,alpha,alpha',alpha'-tetraaryl-2,2-dimethyl-1,3-dioxolan-4,5-dimethanol (TADDOL) series of diols proved to be highly successful hydrogen bonding catalysts for this reaction. Several variables in the reaction were investigated to maximize the yield and enantioselectivity of the desired dihydropyranones. The TADDOL catalyzed HDA reaction proved to be very effective with a wide range of aldehydes, where the reaction with aromatic aldehydes gave good yields and excellent enantioselectivities, while with aliphatic aldehydes, the yields and ee's were just slightly lower. Interestingly, for both aromatic and aliphatic aldehydes it appeared that larger aldehydes provided the desired products in higher yields and ee's compared to the products obtained from the smaller aldehydes. These results illustrated the first highly enantioselective cycloaddition reaction catalyzed through hydrogen bonding, achieving levels of enantioselectivities seen only in metal-based Lewis acid catalysis.; A brief investigation into the mechanism of this reaction addressed several important questions. It was shown that the TADDOL catalyst required both hydroxyl groups to maintain optimal reactivity and selectivity. Based on Non-Linear Effect and preliminary kinetics experiments it appears that the active catalyst is a monomeric species, and that the accumulating adduct does not influence the stereodifferentiating step of the reaction. A crystal structure of the catalyst and an aldehyde supported a single point binding mode of activation for this reaction.; An efficient synthesis was developed to access a series of axially chiral diols that had not been used in a chemical transformation prior to this work. Careful optimization of the 1,1'-biaryl-2,2' -bis(diarylhydroxymethyl) (BAMOL) catalysts resulted in a new class of hydrogen bonding catalysts. The yields of the desired products were significantly higher than obtained from the respective TADDOL catalyzed reactions. The reactivity profile of the catalyst showed that smaller aldehydes gave products with better enantioselectivities than the larger aldehydes. Lastly, several crystal structures of the free catalyst and the catalyst substrate inclusion complex were solved, and supported a single point binding mode of activation. |
