別紙41 信果程博士(英文))Date ofsubmission (month da,ear)ν 10/ 2019

Department
SHINICHnTSUNO
Environmental and Life

SludennD Number

DB5119NAOKIHARAGUCHISciencesSupervisors
へPP11Cant's name

KUMPUGABAHATITHOM

Abstract (Doctor)
Synulesis ofchiral polymeric organocatalysts ofcindlonaAlkaloid De"vatives for
Title ofThesis

小eirApplication in Asymmetric catalysis(シンコナアルカロイド誘導体を用いるキラル高分子有機触媒の合成と不斉反応への応用)

Approx.80o words
The use of chiral polymer catalysts has become one of t11e essential techniques in organicSyntl)esis. Due to the fact ulat, dley can be easily separated froln the reaction mixture andreused for many times.1t is even possible to apply dle polylneric catalysts to a continuous

ao、N system. From the point of vie、N of green chelnistl'y, tl〕e chiral polymeric organocatalysis
method provides a clean and safe altenlative to conventional mea〕ods of asymmetric processes.
Not only t11e practical aspect of the polymeric catalyst but also the particular micro envil'0・
nment dley create in a polymer net圦/ork, that make theln attractive for utilization in organicNactions especia11y in stereoselective synthesis. Design of chiral polymers and t11eir catalytic
Use is no、v extr引nely required in organic synthesis of fine chelnicals.
Cinchona alkaloids are solne of tl〕e lnost ilnportant sources of various kinds of efficient
C11iral organocatalysts、 Each of tl〕e cinchona alkaloids, namely, quinine, cincl〕onidine, quinidine,and cinchonine, contain several functionalities such as secondary alcoh01, quinuclidine, andquinoline rings in addition to tl)e vinyl group. cinchona alkaloids and their derivatives are
Classified as privileged organic chirality inducers, efnciently catalyzing many classes of ω'oanic
reactions in a hig111y enantioselective fashion. As a unique class of bifunctional cinchona
Organocatalysts, cupreines and cupreidines have also been proved as po、verful chiral catalysts
for a 圦lide ω'ray of asylnlnetric transformations. compal'ed to traditional cincl】ona catalysts, one
Of the most noticeable feat1Ⅱ'es of cupreines and cupreidines is that they bear a phenolic oHgroup at d】e C6' position and a free hydroxyl moiety at C9 Position that could be utilized totlme ale steric confon11ation by further functionalization to achieve higher efficiency in asyln・met"c reaction. HO、vever, 10w molecular 、Neights chiral organocatalysts in asymmetric synthesis
Processes are 11indered by mainly t、vo factors; unable to be recycled and low catalyst loading.
Xvith the advancement made in chiral polymeric organocatalysis, cinchona alkaloids as a
Privileged class of chirality inducers have found part in chiral polymeric organocatalysts
design. Even though polymeric organocatalysts in asymmetric syntl)esis, sometimes exhibit poor
reactiV北y by virtual of tl]eir hetel'ogeneity, in some cases, a weⅡ・designed polymeric chiral
Organocatalyst may leads to higher selectivity 、Nith sufficient reactivity in asymmetric
1'eactions. Therefore, CI)iral polymer design, synthesis and their catalytic use; has became an
important tool for understanding the polymeric catalytic efficiency in asy111metnc syntl〕esis forfine chelnicals production.
In this 、vork, we focused on the design and synthesis of chiral polymeric organocatalysts
derived 介oln cinchona alkaloids and, evaluate their catalytic perfonηance in asymmetricMichael addition reactions.

Chapter l shows the generalidea of chiral organocatalysis based on literature revie、V, it
describes tl〕e generation, advantages and applicability of chiral organocatalysts. The whole idea

is categorized into t、vo concepts; 10、v molecular 、veight chiral organocatalysts and polymeric
Chiral organocatalysts for t11eir application in asymmetric synthesis. The importance of thisresearch 、vork is also explained.

Chapter 2 Presents about the cinchona alkaloids and their derivatives as an important toolin
asymmetric catalysis.1n this chapter, the general structure of cinchona alkaloids and t11eir
Catalytic sites have been presented and identified. The application of cinchona alkaloids
del・ivatives in asymmetric synthesis have been summarized. Examples on cinchona alkaloids
derivatives in monomeric, dimeric as we11 as polymeric form of chiral 01'ganocatalysts in diff・
引'ent asymmetric reactions have been explained.1n addition, general synt11etic metl]od010gies
applied in this 、Nork have been brieny explained.

C11apter 3 and 4 describes the development of main・chain C11iral polymeric m'ganocatalysts ofCinchona alkaloids. The repetitive Mizoroki・Heck coupling reaction as catalyzed by pa11adium
Was employed as synthetic method. The C6'・OMe and C6'・OH free containing main・chain
Chil'al polymeric catalysts were synthesized and evahlated in asymmetric Michael addition
reactions. Higher enantioselectivities (up t0 9フツ0 ee) and catalytic activities (up t0 9フツ0 yield)
Wel'e achieved.

In chapter 5, synthesis of cross、1inked chil'al polysiloxanes of cinchona alkaloid derivativeand tl〕eir application to asymmetric catalysis is presented. The platnum catalyzed hydro・Silylation reaction 、Nas used for synthesis of cross・1inked chiral polysiloxanes. The design,Synthesis and catalytic pel'fonnance evaluations in asylnmetric Michael addition reactions havebeen summarized. Higher enantioselectivities (11P t0 99ツ'o ee) and sufficient catalytic activities
Were aC11ieved.

Chapter 6 includes t11e general conclusion on t11e chiral polymers of cinchona alkaloids
estabHshed in tl〕is 、Ⅳork. Their catalytic pelfonnance evaluation based on u〕e factors affecting
their applicability in asylnlnetric synthesis are summarized.1n addition, altenlative synt11etic
approach of obtaining the colnparable main・chain chiral polymers of cinchona alkaloid
derivatives have been shortly explained.

List of publications and experhnental results supporting infomlations of each chapter are
included in the appendices.