This thesis is focused on the development of organic synthetic methodologies by exploiting Achmatowicz rearrangement, which convert biomass-derived furfuryl alcohols to synthetically useful pyranuloses. This thesis consists of three chapters; chapter one presenting the literature review on the transformations of Achmatowicz rearrangement products; chapter two describing the development of C-aryl glycosylation of Achmatowicz rearrangement products with aryl boronic acids through Tsuji-Trost type allyl-aryl coupling; chapter three detailing the development of intramolecular Prins and Friedel-Crafts cyclization of Achmatowicz rearrangement products with tethered alkene, alkyne or arene as π-nucleophile.

C-aryl glycopyranosides are very important structural motifs embedded in many...[ Read more ]

This thesis is focused on the development of organic synthetic methodologies by exploiting Achmatowicz rearrangement, which convert biomass-derived furfuryl alcohols to synthetically useful pyranuloses. This thesis consists of three chapters; chapter one presenting the literature review on the transformations of Achmatowicz rearrangement products; chapter two describing the development of C-aryl glycosylation of Achmatowicz rearrangement products with aryl boronic acids through Tsuji-Trost type allyl-aryl coupling; chapter three detailing the development of intramolecular Prins and Friedel-Crafts cyclization of Achmatowicz rearrangement products with tethered alkene, alkyne or arene as π-nucleophile.

C-aryl glycopyranosides are very important structural motifs embedded in many biologically active natural products and small molecule drugs such as antidiabetic sodium-dependent glucose transporters-2 inhibitors, glycogen phosphorylase inhibitors and protein tyrosine phosphatase inhibitors. In chapter two, we describe the development of a new method for the synthesis of C-aryl glycopyranosides, which features the union of Achmatowicz rearrangement and Tsuji-Trost type allylic arylation with arylboronic acids. We identified two complementary optimal conditions: Pd₂(dba)₃/K₂CO₃/THF and PdCl₂/KF/DCM, effective for allyl-arylation coupling of most electron-rich and electron-deficient arylboronic acids, respectively. It was found that the C4-keto group of Achmatowicz rearrangement products is critical to increase the reactivity of the Pd-π-allyl complex towards arylboronic acids and that phosphine-free palladium catalyst is a must. This new coupling method addresses the major limitations of previous Pd-catalyzed allyl-aryl couplings of 2,3-unsaturated glycosides with aryl Grignard or aryl zinc reagents. We believe this work will have a profound impact on the carbohydrate chemistry.

9-Oxabicyclo[3.3.1]nonane (9-OBN), an oxygen analogue of the widely used reagent 9- borabicyclo[3.3.1]nonane (9-BBN), is a privileged medicinal scaffold present in natural products and pharmaceutical agents. However, there are only few synthetic methods available in the literature. In chapter three, we present the development of a new method for the synthesis of 9-OBN, which characterizes the use of Achmatowicz rearrangement and intramolecular Prins cyclization. For the Prins cyclization, we identified FeCl₃ and FeBr₃ as Lewis acid to smoothly promote cyclization with tethered-alkenes and alkynes to afford 7-chloro- or 7-bromo-9-OBN. In addition, we also extended this method for the synthesis of arene-fused 9-OBNs and 10- oxabicyclo[3.4.1]decanes (10-OCDs) through a mechanistically related intramolecular Friedel- Crafts cyclization. The substrate scope and applications of these two new methods are under investigation in the laboratory and will be reported in due course.