THESIS
2020
xix, 148 pages : illustrations (some color) ; 30 cm
Abstract
Chromanones are an important subgroup of bioactive flavonoids which are widely distributed
in natural products, pharmaceutical molecules and biologically active compounds. Morita-Baylis-Hillman (MBH) carbonates could not only serve as a three-membered synthon when
phosphine catalysts are used, but also a frequently used allylation reagent. Nucleophilic
phosphine-catalyzed reactions of MBH carbonates with chromones could be an appealing
strategy to synthesize chromanone derivatives with two or more chiral centers under mild
conditions. Thiochromanones, the sulfur counterparts of chromanones, also have various
biological activities. Nevertheless, development of asymmetric synthesis of substituted
thiochromanones is greatly inadequate, which may be attributed to the affinity of sulf...[
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Chromanones are an important subgroup of bioactive flavonoids which are widely distributed
in natural products, pharmaceutical molecules and biologically active compounds. Morita-Baylis-Hillman (MBH) carbonates could not only serve as a three-membered synthon when
phosphine catalysts are used, but also a frequently used allylation reagent. Nucleophilic
phosphine-catalyzed reactions of MBH carbonates with chromones could be an appealing
strategy to synthesize chromanone derivatives with two or more chiral centers under mild
conditions. Thiochromanones, the sulfur counterparts of chromanones, also have various
biological activities. Nevertheless, development of asymmetric synthesis of substituted
thiochromanones is greatly inadequate, which may be attributed to the affinity of sulfur with
transition metals, thereby the relevant catalytic reaction might become complicated. Thus, it is
challenging to synthesize enantio-enriched thiochromanones under mild condition.
Chapter 1 gives a short introduction of flavonoids and thioflavonoids. The synthetic approaches
toward the synthesis of substituted (thio)chromanones which serve as a major group among
(thio)flavonoids are also presented.
Chapter 2 introduces a bifunctional phosphine-catalyzed enantioselective [3+2]-cycloaddition
of 3-cyanochromones with MBH carbonates under mild condition. A wide range of special
cyclopentene-fused chromanones can be generated in good to high yield with high
diastereoselectivity and stereoselectivity. DFT calculations have been carried out to investigate
the mechanism, regio- and diastereo-selectivity of the reaction.
Chapter 3 describes a metal free phosphine-catalyzed alkoxy allylation of 3-cyanochromones
with unsubstituted MBH carbonates. The reaction provides a facile method to various 3-allyl-2-alkoxychromanones in high yield with excellent diastereoselectivity. Control experiments
reveal that the nucleophilic addition of chromanone-based intermediate to phosphonium species
take places via an SN2′ pathway.
In Chapter 4, a copper catalyzed asymmetric formal conjugate addition of thiochromones with
terminal alkynes is delineated. The reaction exhibits a good tolerance on functional groups with
different steric and electronic properties. Control experiments show that the counter ion from
silane is crucial for the reaction. Derivatizations of some products have also been carried out to
demonstrate that the process enables efficient access to diverse thiochromanone derivatives.
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