Development of Functionalized Chiral Allylboranes via Allene Hydroboration and Applications in Natural Product Syntheses.

摘要

The asymmetric carbonyl allylation reaction is an important transformation in organic synthesis. Together with the asymmetric aldol reaction, it represents one of the most widely adopted methods for the syntheses of acyclic molecules with contiguous stereocenters. One disadvantage of the vast majority of prior allylation reagents is that homoallylic alcohols with terminal olefin are generated. Several step manipulations are often required for further carbon--carbon bond formation or extension of the vinyl group.;Asymmetric carbonyl allylation with bifunctional allylmetal reagents could provide a viable solution to this limitation. Allylation of aldehyde substrates with bifunctional allylmetal reagents could provide homoallylic alcohols with defined stereochemistry through proper selection of the chiral auxiliaries, ligands or catalysts associated with these reagents. More importantly, the olefin units in the homoallylic alcohols generated from these reactions are functionalized, and are poised for a variety of subsequent transformations. Compared to the conventional allylmetal chemistry, allylation reaction with bifunctional allylmetal reagents provides an unparalleled platform for late stage fragment assembly in complex molecule synthesis by taking advantage of the reactivity of the functionalized olefin unit. Adaptation and further exploration of the chemistry should lead to significant simplification of strategies used for the syntheses of polyketide natural products.;In the following chapters of the thesis, we describe our efforts toward the enantioselective syntheses of several bifunctional allylmetal reagents and applications of these reagents in polyketide natural product syntheses.