Selective Transformations of Unprotected Carbohydrates Using Organoboron Compounds to Modulate Hydroxyl Reactivity

摘要

Regioselective glycosylation of unprotected glycoside substrates has emerged as an attractive strategy for streamlining the synthesis of oligosaccharide targets. However, differentiation of multiple potentially reactive hydroxyl (OH) groups is not always straightforward. The use of small organic molecules to enforce regiocontrol in glycosylation reactions by enhancing the differences in reactivity of carbohydrate OH groups or by altering the innate regioselectivity of the substrate is a useful strategy. The work presented in this thesis describes how the interactions between carbohydrates and organoboron compounds can be used to promote selective transformations of unprotected glycosyl acceptors.;Chapter 1 describes how organoboron-promoted regioselective glycosylation reactions can be used to streamline the synthesis of oligosaccharide targets by minimizing protection/deprotection steps. An initial regioselective glycosylation allows differentiation of the remaining OH groups of the disaccharide-derived diols, enabling further selective transformations through substrate controlled processes.;Chapter 2 describes the development of a protocol for the regioselective protection of carbohydrate derivatives using boronic acids as temporary blocking groups which can be recovered/recycled. Boronic ester formation with carbohydrate-derived diols attenuates the nucleophilicity of the boron-bound alkoxides, permitting selective functionalization of free OH groups.;Chapter 3 describes a novel boronic acid-mediated sequential functionalization protocol. Exploitation of the complementary reactivity of tricoordinate (protecting group) and tetracoordinate (activating group) boronate complexes allows multiple bond-forming reactions to be carried out without the need to isolate intermediate compounds. This allows the production of highly functionalized glycoside products directly from unprotected starting materials.;In Chapter 4, strategies for the selective activation of 1,2- or 1,3-cis-diol groups are presented. The interaction between the glycosyl acceptor and the boronic- or borinic acid enables selective activation of one of the two diol groups. This chapter also describes how tuning the properties of a borinic acid catalyst can alter the regiochemical outcome of glycosylation reactions.