Date of submission uanuary 7,2022)

Depa111nenι

Of

Applied clwmistry

StudentlD Number

18叫02

PI'of. Dr. Naoki Haraguchi

and Life science

Supe1刃isor
Pplicant'S

Prof. Dr. Hideto Tsuji

MITHUNKU八仏RDEBNATH

nalT】eAbstract (Docto"
Title ofThesis

Development ofpolymer Microsphere・immobilized chiral pyrrolidine catalyst
and lts Application to Multistep one・pot Asymmetric synthesis

Approx.80O W01'ds

Transformation reaction 、 ,ith chiral catalyst is of increasing importance in 御'ocess chemistry inOrganic synthesis、 The most crucial cha11enge is developing a suitable synt11esis procedure, that canPr0小Ice the desired optica11y active compounds with lo、N enviromれe川alimpact, high economic
feasibiⅡty, and high efficiency.1f multiple transf0Πηation reactions using chiral catalysts can beC01栂ecutively carried out in a one l'eaction vessel, in that case, a highly e価Cient organic synthetic
Process can be realized. unfortunately, one ofthe Ⅱmitations is that multゆle catalysts 、¥ith contral'y
Propel'ties (e.g., acidic, and basic, oxidative, and reductive) cannot be used simultaneously"site isolation" is an elfective way to a110、v multiple catalysts to operate independently. several
Site isolating materials al'e available, but their synthesis methods are comPⅡCated. Therefore,
developing a general method that can smoothly perfonれ one・pot catalytic reactions based on site
isolation is strongly desired.

Polymer microspheres can be one of the promising candidates as the site isolating m飢erial
They possess exciting features such as large specific surface area, high meC1徐nical strength, highdispersib畄ty, insolubiⅡty, a simple separation process, 10、 ' S、Ne1Ⅱng tendency, and easy
Preparation. hl this research, we have tried is to establish a one・pot reaction system based on site
isolation using crosslinked polymer microsphere as a new site isolating matel'ial,、Nhich leads to ahighly e舗Cient one・pot organic synthetic process

Chapter l describes the σeneralintroduction and backgrolmd ofthe thesis
Chapter 11 describes the synthesis of crosslinlくed polymer microsphere・immobilized chiral
Pyrrolidine catalysts and t11eir application to asymmetric Michael addition reactions. The polymer
microsphere、immobiⅡZed chiral pyrrolidine catalysts have been prepared via the precipitatlon
Polymerization using divinylbenzene, a comonomer, and a methacrylate monomer bearing a chiral

N、Boc pyrr0Ⅱdine moiety, f0110、ved by the removal of the N・Boc group. The resulting polymericCatalystS Ⅵ,ere characterized by scanning electron microscopy, Fourier transfonη infrared
Spectroscopy, and elemental analysis. AR引'the successful preparation ofthe polymeric catalyst, theCatalytic pelfon11ances of the polyme"c catalysts 、Nere evaluated by carrying out asymmetricMichael addition reactions between aldehydes and alkyl vinyl ketones. The reaction proceeded、¥川l exce11ent yield and enantioselectivity when the polymeric catalysts were hydrophobic because
the hydrophobic nature of the catalysts provided the suitable microenvironment for the reaction toOccur. The effect ofthe molar ratios 、Nithin the catalyst, catalyst loading, temperature, solvent, andSubstrate on the reaction yield and enantioselectivity 、vere investigated in detaⅡ. polar andnon、polar organic solvents significantly a仟ected the reaction yield and enantioselectivity.1n thePresence of polar solvents, the yield of the Michael adduct de引'eased signiacantly due to therestricted dlspersion of hydl'ophobic polymeric catalysts in t11e reaction medium. on the other
hand, the presence of non・polar organic solvents the yield ofthe reaction slightly increased but not
Satisfact01'ily due to the insolubility of the cocatalyst in non・polar solvents. The solvent・freeCondition 、Nas best suited for this reaction system. The recovel'y and reuse of a polymer

microsphere、immobilized catalyst W引'e performed, and the catalysts retained its original catalytic
activity up to nve cycles

Chapter 111 describes the development ofone・pot asymmetric two steps reaction system based
On site isolation using crosslinked polymer micl'osphel'e as the site isolating pl'ecursor. The site
isolation potential of the crosslinked polym引' microspheres 、vas demonstrated by cal'1'ying out aOne、pot t、vo steps deacetalization・asymmetric Michael addition reaction using crosslinked polymer
microsphere、immobilized sulfonic acid and chiral pylT0Ⅱdine catalysts. The first step of lhe
One、pot reaction sequence is the deacetalization of propionalde11yde diethyl acetal catalyzed by theacid catalyst to produce the intermediate compound propionaldehyde. The second step is theasymmetric Michael addition between the produced intermediate compo{md propionaldehyde andmethyl vinyl ketone using chiral basic pyrrolidine catalyst. The pair of lo、V・molecular・、和eight acidand base catalysts cannot catalyze the reaction due to the neutl'alization reaction among them. The行nal product 、vas obtained 、vith good yield and enantioselectivity when the acid and baseOrganocatalysts are cl'osslinked polymer microsphere・immobilized. This result indicating that using
Crosslinked polymer microspheres site isolation can be achieved. The best catalytic activity wasfolmd for the hydrophobic chil'al pyrr0Ⅱdine catalyst and polymer microsphere・immobHized
Sulfonic acid catalysts pair 、V川〕 a good yield (829"0) and enantioselectivity (91%). The recovery and1'eusability ofthe best catalysts pail' wel'e also performed, and tlwy retained their original catalytic
activity in the next cycles

Chapter lv describes development of one・pot three steps asymmetric reaction based on site
isolation using heterogeneous acid and base catalysts. The first step of the reaction, i.e., theasymmetric Michael addition reaction between the lert‑butyl acetoacetate andira"S、cinnamaldehyde 、Nas catalyzed by the chiral pyrrolidine catalyst. Then, the acid catalyst
Sequentia11y catalyzed the r引ηaining two steps, i.e., hydrolysis and decarboxylation reactions. The10、¥、molecular、、和eight acid and base catalysts pair even lineal' polymer・immobilized acid and base
Catalyst cannot a仟ord the fina1 御'oduct due to the deactivation of the catalytic sites byneutralization reaction. using the polymer microsP11ere・immobilized chiral pyrrolidine catalyst andSⅡica gelimmobilized acid catalyst pair, good yield and exce11ent enantioselectivity 、Nere obtained
Using the combination of polymer microsphere and silica gel, site isolation was achieved due tothe insolubility and the 3・dimensional structure of the crosslinked polymer mlcl'osphere and SⅡica
gel microsphere. The active sites of acid and base cannot diffuse into each other and thus site
isolation accomPⅡShed

Chapter v describes the generalsummary ofthe thesis 、Nork.