Development of novel strategies based on Lewis acid and transition metal mediated stereoselective c-glycosylation

Abstract

The significance of C-glycosides has stimulated a wide interest in the development of C-glycosylation methods. Among them, Lewis acid and transition metal mediated direct attachment of carbon nucleophiles to sugar anomeric carbon center to produce 2,3-unsaturated glycosides and saturated, fully oxygenated glycosides are probably the most widely used methods. This thesis work focuses on the development of new methodologies in Lewis acid and transition metal mediated stereoselective C-glycosylation and application of these methodologies to natural product synthesis.

In the first part, a new method towards 1,2-cis and 1,2-trans C-mannosylation based on BF3•OEt2 promoted directed coupling of organotrifluoroborate reagents with mannosyl fluorides is demonstrated. This methodology was also applied into the α-C-glycosylation for D-glucopyranose, D-galactopyranose, D-mannofuranose and D-arabinofuranose. In the second part, a highly β-selective C-glycosylation via palladium-catalyzed decarboxylative allylation is introduced. The reaction mechanism was further studied by experimental and DFT calculations. It was found that the reaction proceeded through an ionization-allylation-decarboxylation sequence via an outer-sphere mechanism. In addition, the methodology was also applied in normal pyran systems to generate cis-2,6-disubstituted tetrahydropyrans in high yields and exclusive selectivity, providing a new facile mode of access to naturally occurring cis-2,6-tetrahydropyrans. Furthermore, the applicability of these methodologies was examined by the total synthesis of (+)-varitriol, (±)-centrolobine, decytospolide A, B and aspergillide A