Date of submission: septembel' 24,2019
DepaHmentof
Applied C11emistry

StudentlDand life science

Applicant's name

ASSOC. prof Dr. NaokiHal'aguchi

169402
NumberSupervis01'S

Prof. DI'. shinichi ltsuno

Prof. DI'. Hideto lsuji

MD.WAI,1U11AH

Abstract (Doctor)
Title oflhesis

Synt11esis offunctional c01'e・corona polymer Micl'osphere and lts Application toAsymmetric organocatalysis

Approx.80o words
Chil'al organocatalysts have been received considerable attention in asymmetric synthesis because of
their advantages ofbeing cost e仟ective, readily available, non‑toxic and envi】'onmental fl'iendly. Amonga val'iety of chⅡ'al 01'ganocatalysts, chlchona alkaloidS 引'e one of 小e ef6Cient m、ganocatalysts in theasymmetl'ic 01'ganocatalysis which are available m pseudoenantiome"c f01'ms, due to their commercial
availability at low prices, stability and easy handling in lab01'at01'y, as 、veⅡ as t11eil' colwenientmodi6Cations by simple l'eacti011S. chlch011α del、ived quatemal'y ammonium salts al'e one of the mostPopular organocatalysts in the field of asymmet"c catalysis especiaⅡy for tl〕e synthesis of 山lnatul'al
α・amino acids. chiralimidazolidin・4‑ones and 小eir salts,01'igina11y developed by MacMi11an andCO・workers, are also one ofthe most impoTtant classes ofchil'al oTganocatalysts
Immobilization of a chlral organocatalyst onto a heterogeneous supp01't l'epl'eS引〕ts an attl'active
appl'oach for catalytic asymlnetric reactions from a viewpoint of its sustainability. Altl〕ough the】'e 11ave
been n山1〕erous reports on covalendy bonded both polylner・i】nmobilized chiral quatel'n引、y ammoniumSalt and MacMi11an catalyst for asynU11etric alkylation and the Diels、Aldel'1'eaction, respectively, theseheterogeneous catalysts sometimes 0仟el'inh引、ent disadvantages, such as low selectivity and low catalytic
activity.1hese can be interpreted in ten)]s of direct covalent‑bonding of 01'ganocatalysts to the supp011
matenal, decl'easi】1g the intl'insic properties of stel'ic sensitivity of 01'ganocatalyst on asymmetric
Syn{hesis.

10 solve the above probleln, an altemative strategy involving the ionic hl〕mobilization of anOrganoca始lyst on a suppo】't uslng an ion・exchange l'eaction has bee11】'ep011ed、 1his method is a f会Cile andgeneraltechnique f01'the mUηobilization of ammoni山れ onto sulfonated polymers regal'dless of kinds ofammo】]ium and sulfonated polyme】', WI〕ich can be employed in mild conditions.11] some cases, theseionica11y immobilized 01'ganocatalysts also showed low catalytic activity、Neve】'theless of tl]e efficiency of polymel'1nicl'osphere as polymer support, t11el'e is n01'ep01't on theimmobilization of cl】il'al cinclwnidinium sak 01' MacMi11an catalyst onto polymel' micl'OSP11ere
Monodispel'se sulfonated c01'e‑C01'ona polymel' micl'osphe】'es seem to be suitable solid‑supports for theionic immobilization of chil'al organocatalysts because ofuleir hioh S山'face al'ea, facile dispel'sibility、 andhigh medlanical and themlal stability.1n addition, an advantage of polymel' microspheres is the ability toControl t11eir hydl'ophilic・hydrophobic bala】1Ce, which offers S山table microenvironments f01' catalytic
asylnmetl'ic reactions.1heref01'e, synthesis of weⅡ・defined c01'e・corona polyma' microsphere‑Suppolted

Chiral 01、gancatalyst is a new idea in asymmetrjc catalysis for obtainmg optica11y active compounds. TO
Investigate the e仟ect ofthese polymeric 01'ganocatalysts in asymlnet】'ic ca仏lysis,杁ノe have developed bothCore、corona polymer microsphere‑Suppolted chh'al cinchonidhlium salt and MacMiⅡan ca仏lyst andapplied them as heterogeneous catalysts in the asymmetric alkylation and the Diels、Alder reaction,
1'espective】yChaptel' 1 describes the gen引'ation introduction and background ofthis thesis work
Chapter 11 describes the synthesis of nalTO、vly dispel'se functional polymer micl'ospheres having
benzyl halide moiety by precipitation polymel'ization of various comonomel'S (styrene (st), methyl
metha引'ylate (MNIA), or 2‑1〕yd】'oxyethy1 1netha口'ylate (HEMA)), divinylbenzene (D＼/B) with
4・vinylbenzyl chloride (VBC). we have also successfuHy syn廿lesized low cross・1inked polymel'
micl'osphel'es using lo m01% of crosslinker (DVB a11d a divinyl cl'osslinke" by precipitationPolymerizauon and transf0帥ation Teaction. The nat山'e of comonomer and 小e molan'atio of monome】'Saffected d〕e yield and diamet引' ofpolymer pal'ticles
Chapter 111 PI'ovides a novel strategy f01' t11e synthesis of we11・de6ned ha11'y polyl】1el' or c01'e c01'ona
Polymel' microsphel'es by pl'ecipitation polymerization and surface‑1nitiated atom u'ansfer l'adical
Polyme血atio"(SI・AT即).1he u, of g】'a介ed polyme,' can be conれ'011ed up t0 15,ooo g mov byd松noing u】e Mn, and tl】e u゛/U,Ⅵ,as lower than l.30 、¥hen M/1 f 150,1n tl】is chapter, monodispel'seSulfonated c01'e‑corona polymer mjcrosphel、e、vasalso successfUⅡy synthesized 介'om the gl'a介

Copolymeriza{ion of an achil'al monome】' and phenyl p・styl'enesulfonate wjth polymel' m】CI'OSP11el'e1〕aving benzyl chlo】'ide moiety as a macl'oinitiator by sl・ATRP, f0ⅡOwed by the treatment NaoH.1hegl'a介 Copolyme】'ization of styl'ene and phenyl p‑styrenesulfonate pl'oceeded in a contl'0Ⅱed manner,a仟ording weⅡ・de6ned

Core‑corona

Polymer microsphere when poly(DVB・HEMA・VBC) orPoly(DVB・st・VBC) micl'osph引'e was used as a macl'oinitiator
Chapter lv descl'ibes t1祀 Synthesis of c01'e・C01'ona polymel' microsphel'e‑SUPP01'ted chiral
Cinchonidini山1〕 salt by t11e ion exchange l'eaction of sodi山1〕 sulfonate moiety at t11e side cl〕ajn of corona
With chil'al cinchonidini山11 Salt,、¥hich 、vas applied as dln'al hetel'oge】1eous 01'ganoca仏lyst in t11e
asymmetl'ic alkylation of a glycine del'ivative to give hjgh yields (up t0 99%) and ena爪ioselectivites (UPto >99ツ0 ee).1he effヒCt of nat山、e and size of c01'e,1]atul'e and length of c01'ona, gl'a丑ino density, as weⅡ
as the degl'ee of cl'osslinking on tl〕e catalytic Nactivity was invest喰ated in deねH in this chaptel'.1heCatalyst could be easily and quantitatively l'ecovered fl'om reaction mixt山'e and l'eused sevel'altimes
Without loss of dle enantioselectivity. To our knowledge, this is the first l'ep01't of c01'e、C01'ona polymer
micl'OSPI)引'e・SUPP011ed clnclwnidinium salt in the asymmetl'1C alkylation
Chapter Y descnbes the synthesis of c01'e・corona polymel' micl'osphel'e・SUPPO】'1ed MacMi11an
Caねlyst by t11e neutl'alization reaction of sulfonic acid moiety at t11e side chain of c01'ona with MacMi11an
Catalyst preC山'sor.工入le evaluated their catalyuc e価Ciency in t11e asymmetl'ic Diels‑Aldel'1'eaction andObtained the desired adducts in good yield (up t099ツ0) with exce11ent ee value (up t097% ee (e入'0) and>99% ee (endo)).11〕e c01'e and c01'ona (kinds of monomel', d稔meter, and length ofcor01〕a) significantly
affected on 小e catalytic activity. The catalyst could be l'eused several times without loss of t11e
enantioselectivity

Chapter vl describes the genel'al summary oft11is thesis work