Studies Toward The Use Of Non-conventional Hydrogen Bonding In Chiral Lewis Acid Catalyst Design ; Strained Silacycles In Organic Synthesis : Novel Reagents For The Asymetric Allylation Reaction

The first part of this thesis details our studies toward the use of the formyl hydrogen bond as an organizing element in the design of a chiral Lewis acid for carbonyl addition reactions. The assignment of a hydrogen bond interaction to the formyl hydrogen is still in contention, and some of the arguments are presented. However, there are ample evidences indicating that the formyl group participates in attractive interactions. A series of chiral pyridine-oxazoline ligands, bearing appropriately situated hydrogen bond acceptors for the aldehyde substrate, were treated with various metals to provide chiral metal complexes, which were screened for asymmetric, catalytic activity. The allylstannation reaction of benzaldehyde in the presence of a Fe(SbF6)2 complex proceeded in 13% ee. The hetero Diels-Alder reaction of benzaldehyde and Danishefsky's diene in the presence of a Cu(OTf)2 complex proceeded in 23% ee. Owing to the modest enantioselectivities exhibited by these complexes, we could not conclusively attribute the observed asymmetric induction to formyl hydrogen bond interactions.

The second part of this thesis presents the development of a novel class of strained silacycle reagents for the asymmetric allylation of aldehydes. Strain-release Lewis acidity was postulated as a factor in the reactivity of the chiral allylsilacyclopentane reagents, which has important implications for the application of the concept in synthetic chemistry. A stable allylsilane reagent, which used pseudoephedrine as a chiral controller, added to aliphatic aldehydes at -10°C to provide homoallylic alcohols in good yields (70--80%) and high enantioselectivity (87--96% ee). A stable crystalline diamine-modified allylsilane reagent was successful in the allylation of both aromatic and aliphatic aldehydes, providing good yields (61--90%) and excellent enantioselectivities (95--98% ee). These reagents, featuring high selectivity, a general substrate scope, procedural convenience, and low toxicity, are of good synthetic utility and represent a significant advancement in the development of the asymmetric allylation of aldehydes. Studies toward the asymmetric allylation of ketones and propargylation of aldehydes are also presented.