I. Stereoelectronic factors in the stereoselective epoxidation of glycals and 4-deoxypentenosides II. Stereoselective glycosylations using glycosyl dithiocarbamates
Abstract
4-Deoxypentenosides (4-DPs) are unsaturated pyranoside derivatives bearing a strong resemblance to glycals, but possess heteroatomic substituents at the anomeric position rather than carbon. Fully substituted and cis -disubstituted dihydropyrans are subject to a "majority rule", in which the epoxidation is directed toward the face opposite to two of the three groups. Systematic removal of substituents at various positions enables us to address the relative impact of each on facioselectivity. We have consequently used a computational approach based on π-polarized frontier molecular orbital (PPFMO) theory, which can suggest an electronic polarization to one face of the enol ether based on the influence of local substituents. Our results to date confirm that the epoxidation results cannot be explained solely by a single structural or electronic factor, suggesting the participation of all groups on the net polarization in the sigma-bond reactivity of these enol ethers. We find that while the C3 allylic substituent has the strongest directional contribution, the remaining substituents can work in concert with each other to completely override the allylic stereodirecting effect maintaining the high facioselectivities. The results discussed in Chapter II demonstrate the efficiency of the copper mediated glycosylation using dithiocarbamate glycosides as donors towards the one-pot synthesis of α-linked oligosaccharides without anchimeric assistance. The yields are improved significantly over the ZnCl 2-mediated glucosylation of α-1,2-anhydrosugars. The mild reaction conditions enable coupling with acid-sensitive glycals as both donors and acceptors. The reaction conditions were optimized to compensate for the lower reactivity of the disaccharide DTC donors. The practicality of this strategy was demonstrated in the synthesis of Pregnane glycosides. The newly generated free C2 hydroxyl group can be immediately used as a point of branching, avoiding tedious protecting group manipulations.
Degree
Ph.D.
Advisors
Wei, Purdue University.
Subject Area
Organic chemistry
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