Enantioenriched amino ketones are convenient building blocks for a variety of synthetic transformations as well as important structural features in a wide array of natural products. N-heterocyclic carbene (NHC) catalyzed benzoin reactions are of great strategic value for obtaining such motifs. Initial efforts focus on a chiral auxiliary approach towards the NHC-catalyzed aza-benzoin transformation. It was investigated whether enantio-enriched α-aminoketones could be obtained using t-butanesulfinimines under NHC-catalyzed reaction conditions. Moderate yields and diastereomeric ratios are obtained between furfural-derived aldehydes and aldimines using this method. The unsatisfactory results prompted further investigation into alternative synthetic methods towards enantioenriched amino ketones. The chemo- and enantioselectivity of cross-benzoin transformations has been the major focus of several recent studies. In contrast, the use of chiral aldehydes in diastereoselective cross- benzoin reactions has received scant attention. This may be explained by the poor reactivity of sterically hindered substrates and/or difficulties in controlling the chemoselectivity. N-Protected α-amino aldehydes, owing to a synergistic balance between their electronic and steric properties, were used to address the chemoselectivity issues associated with NHC-catalyzed cross-benzoin reactions. This thesis describes the first examples of NHC-catalyzed chemo- and diastereoselective cross-benzoin reactions between two aliphatic aldehydes. The optimized reaction conditions can deliver a variety of enantio-enriched α-hydroxy-β-amino ketones with excellent chemoselectivity and good to excellent diastereoselectivity. Having developed viable methodologies to access enantio-enriched amino diols, the application of these methods was investigated in the synthesis of two natural products: D-arabino-phytosphingosine and hyacinthacine A1. Progress towards completion of the synthesis as well as future directions are discussed. With an emphasis on expanding the scope of the application of α-amino aldehydes in NHC-catalyzed transformations, this thesis concludes with a general discussion and proposal for future directions.
cross-benzoin reactions, aza-benzoin reactions, N-heterocyclic carbenes, organocatalysis, D-arabino-phytosphingosine, hyacinthacine A1
Doctor of Philosophy (Ph.D.)