Development of transition metal catalyzed C-C and C-P bond forming reactions for efficient synthesis of biologically active compounds생리활성 물질 합성을 위한 전이금속 촉매를 이용한 탄소-탄소와 탄소-인 결합형성에 관한 연구

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Chromenone derivatives have been extensively investigated in the area of medicinal chemistry, material chemistry and biochemistry. Although many strategies for the synthesis of the chromenone derivatives have been established, the scope of reactions has been somewhat limited due to the harsh conditions, prefunction-alization, poor substituent tolerance, or low chemical yield. In this context, developing efficient methods for the synthesis of this derivatives via C-H activation is highly desirable in terms of efficiency and practicality. Inspired by the recent advances in this area, we have developed the general and atom-economical synthesis of chromenone derivatives for the efficient identification of biologically active compounds. Part 1. Development of Palladium Catalyzed C-C Bond Forming Reactions for the Synthesis of Fluorescent Coumarin Derivatives Coumarins constitute a major class of naturally occurring compounds and privileged medicinal scaffolds that exhibit a broad range of biological and pharmaceutical properties, including anti-HIV, anti-tumor, anti-hypertension, anti-arrhythmia, anti-inflammatory, anti-osteoporosis, anti-septic, analgesic and anti-coagulant activities. Coumarins are also most important class of fluorophores, and they have been extensive-ly investigated as powerful tools for biological applications, especially for live cell imaging. Although many strategies for the synthesis of the coumarin derivatives have been developed, the scope of such condensation reactions has been somewhat limited due to the harsh conditions, multistep synthesis, poor substituent tolerance, or low chemical yield, and therefore, the synthesis of some derivatives continues to pose a challenge. In this regard, developing alternative efficient methods for the construction of this struc-tural motif is a topic of immense importance. The direct functionalization of C-H bond is an exceedingly valuable process in the context of contemporary organic synthesis. In particular, direct (hetero)arylation and alkenylation of heteroarenes using transition-metal catalysts has found widespread use in synthesis for the construction of complex frameworks. Inspired by the recent advances in this area, we have developed the general and atom-economical synthesis of fluorescent coumarin derivatives for the efficient identification of biologically active compounds. Part 2. Development of Transition Metal Catalyzed C-C Bond Forming Reactions for the Synthesis of Flavones Flavones, known as 2-phenylchromones, are abundant in numerous naturally occurring products and have been shown to display a variety of biological activities. As a consequence, synthetic approaches to flavone skeletons through efficient bond formation have been extensively investigated, and a number of classical synthetic approaches to this family of compounds have been developed. Despite these advances, most methods suffer from the drawbacks of multiple steps, harsh reaction conditions or toxic CO gas. In view of high synthetic utility, the most straightforward method for synthesizing flavones or 2-arylchromone deriva-tives would involve the oxidative cross-coupling of chromones with simple arenes via a double C-H bond functionalization. we have developed the first example of a C2-regiocontrolled C-H functionalization of chromones that enables facile oxidative cross-coupling reactions with unactivated arene components. Addi-tionally, we also developed the Ru(II) catalyzed alkenylation of flavone by utilizing the carbonyl moiety as directing group for further functionalization of these derivatives. Part 3. Development of Rhodium(III)-Catalyzed Direct C-H Phosphorylation of Arenes Arylphosphonates and their derivatives have been extensively investigated in the area of medicinal chemis-try, material chemistry, catalysis and ligand. Despite the importance of this derivatives, direct C-P bonds for-mation via directed C-H activation is quite challenging because of the strong coordination ability of phos-phrous reagent to transition metals. Although, several groups improved the efficiency in direct C-H phos-phorylation, these methods still suffered from limited substrate scope and functional group tolerance. In this regard, further development of efficient C-H phosphorylation reactions using other transition metal catalysis is highly desirable to expand the scope and utility of this synthetically valuable transformations. In this con-text, we were particularly interested in the use of Cp*Rh(III) catalysts for directed phosphorylation of aro-matic C-H bonds due to its high activity, selectivity, broad substrate scope, mild reaction conditions and functional group tolerance. We developed the first example of Cp*Rh(III)-catalyzed C-P bond formation reaction with α-hydroxylalkylphosphonate. Significantly, many different directing groups (oxime, pyridine, anilide, amide, imine) can be applied in this new C-H phosphorylation reaction, and the C-H phosphorylation is suitable for functionalization of bioactive complex molecules that would be challenging with other transi-tion metal catalysts.
Advisors
Hong, Sungwooresearcher홍승우researcher
Description
한국과학기술원 :화학과,
Publisher
한국과학기술원
Issue Date
2016
Identifier
325007
Language
eng
Description

학위논문(박사) - 한국과학기술원 : 화학과, 2016.2 ,[v, 78 p. :]

Keywords

Transition Metal; Cross-Coupling Reaction; Alkenylation; Arylation; Phosphorylation; 전이금속; 교차 짝지음 반응; 이중결합 도입; 아릴그룹 도입; 인그룹 도입

URI
http://hdl.handle.net/10203/222503
Link
http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=648314&flag=dissertation
Appears in Collection
CH-Theses_Ph.D.(박사논문)
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