THESIS
2020
xii, 143, 300 pages : illustrations ; 30 cm
Abstract
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...[
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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: Pd
2(dba)
3/K
2CO
3/THF and PdCl
2/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 FeCl
3 and FeBr
3 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.
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