別紙41 (課程博士(英文))Date ofsublnission (month da,ear)

JUI B,2018

Department

Environmentaland Life

StudentlD Numbel

D159403

SciencesSupetvisors

Dr. shinichi Rsuno

Dr. Naoki Haraguchi
Mohammad shahidUⅡah

PP11Ca11t's name

Abstract (Doctor)
Iitle oflhesis

Synthesis ofcinchonaAlkaloids・dedved chiral squaramide polymers and TheirApplication
to Asylnmetdc catalysis

一ξ'气

Approx.80o words
Cinchona alkaloids・dedved sqU雛amide containing chiral main・chain polylners have been successfU11y
Synthesized and applied to asylnlnetlic catalysis. Quinine, quinidine, cinchonidine and cinchonine are theComlnon commercia11y available cinchona alkaloids. These are one ofthe popular s0山'ces for chitality inducers
in the field of asylnmetric catalysis. cinchona alkaloids have vadouS 61nctionalities including a quinuclidine
tediary nitrogen, a secondary alcoh01, a quinoline dng and a tennmal olefln m thelr structure. The chelnicalmodifications of the 丘lnctionalities enable us to desi即 new catalysts. Thus, severa11nodi丘Cations have been
already done by differentresearch goups and sy11thesis ofmany monolneric and dimedc organocatalysts havmg
Cinchona squaralnide moieties have also been reported. The acidic NH of the squaralnide can act as a H‑bonddonor, whereas the tediary nitrogen of the quinuclidine of cinchona alkaloids may acts as both a H・bondacceptor and a base.1hus the cinchona squaramide can act as a bi丘lnctional H・bonding organocatalyst in theasylnmetric transfonnations.

■一,︑

Cinchona derived squaralnides can act as the e缶Cient organocatalysts in dia'erent asymmetdc
transfonnations. Although several works have been reported with the low・molecular・weight squaralnide
Catalysts dedved 6'om cinchona alkaloids,1imited number of works have been canied out in tl]e sy11thesis andapplication of chlral polylnenc organocatalyst on the asymmetric transfonnation. cinchona alkaloids containing
Polystyrene・supported side・chain type polylnehc catalysts have been already synthesized and appHed on
asylnmetdc reactions.1n case ofpolylner‑suppoded catalysts, aexlble and stedca11y irregular stNctures are used.
On the other hand, the chiral main・chain polymedc organocatalysts contain the dgid and stedca11y regular
St川Ctures in their backbone. This approach is more suitable to lnaintain the catalytic environment of themonomeric catalysts into the polylnedc catalysts. The main・chain cinchona squaralnlde polylners can act as agood organocatalysts in asylnmetric reactions due to the creation of a suitable microenvlromnent by thePolymers which is very lmportant for the stereoselectivity of the catalysts. The modi6Cation of a
Inicroenvironlnent ofpolymers is very important and itis possible to controlthe microenvlronlnent precisely ln
the chiral main・chain polymedc catalysts. The enantioselectivity of low・1nolecular・weight monomedc catalysts
Can be maintained in the corresponding polylnedc catalysts due to the fonnation of hgid and steHcaⅡy regular
backbone in the polylners stNcture. cinchona squaranlide polylnedc catalysts can be prepared by theinc0印oration of low‑molecular‑weight dilneric squaralnide, using suitable polylnedzation technlques underOptimalreaction conditions.

Therefore, stNctural design and S沖thesis of main・chain chiral polylnedc organocatalysts are very lnuch
attractive 負eld ofresearch in asymlnetHC S沖thesis to obtain enantiopure organic compounds. To understand theeaect of main・chain chlral polymeric or8anocatalyst in asylnmeh'ic synthesis, we have S沖thesized several
Cinchona dedved squaralnide main・chain polylners using Nlizoroki・Heck and ADMET polymedzation n〕ethods
and succesS6、111y applied in the enantioselective Michael addition reactions.
In this thesis, chapter l presents the generalintroduction which includes the stmctural features of cinchona

alkaloids, chiral organocatalysts, polylnedc organocatalysts and the background ofthis thesis work. This chapter
also indudes the generalreviews aboutlow‑1nolecular‑weight cinchona alkaloids squaramide catalyzed di丘erent
asymmetdc reactions, including Michael addition reaction, Friedel・crafts reaction, strecker reaction, andMannich reaction.

Chapter 2 Presents the synthesis of novel chiral squaramide polylners by the reaction of cinchonadelived・squaramide and vaHous aromatic diiodo colnpounds using Nlizoroki・Heck polylnerization. TheMizoroki‑Heck reactions between the double bonds of the cinchona・based squaralnide and aromatic diiodides
Proceeded smoothly to give cinchona squaramide chiral polymers. The asylnlnetric Michael addition ofβ・ketoesters to nitroolefins was succesS丘1Ⅱy catalyzed by the squaramide polylners t0 部Ve the conesponding
Michael adducts in good yields and exce11ent enantioselectivities of up t0 97% ee. As the polylnehc catalysts、vere insoluble in colnmonly used organic solvents,these were recovered and reused without any loss ofcatalytic
actlvlty.

Chapter 3 describes the synthesis ofnovel chiral polymers ofdiamine connected cinchona squaramides using
Mizoroki・Heck poly111edzation as highly e伍Cient catalysts in the asy1111netric Michael addition reaction. we

designed novel cinchona squaralnide din〕ers that contain t、vo cinchona squm'alnide un北S connected by dialnines.
Ihe olefinic double bonds in this dilner 、vere used for Mizoroki‑Heck polylnedzation with arolnatic diiodides toglve the conesponding chiral polymers in good ylelds.圦le have suNeyed the effect of tl〕e chiral polylner
S{ructure on the catalytic activity and enantioselectivity of the asylnmetdc reaction. The novel squaralnides andalso polylners were appHed in asymmetdc Michael addition of β・ketoesters to nitroolenns to obtain 壮le adducts
︑{︑JJ<Jin good yields with exce11ent stereoselectivities.1n this case the polylneric catalysts were recovered and reused/for severaltlmes.

Chapter 4 describes the sy11thesis of cinchona alkaloid・dedved novel chiral squaralnide polylners by acyclic
diene metathesis (ADMET) polylnedzation and their application to asymlnetric catalysis. The tlrst S沖thesis ofhigh molecular weight cinchona alkaloid・dedved chiral squaramide polylners by ADMET polymehzation is
rep011ed, using the Hoveyda・GNbbS 2nd generation catalysts (HG2).叉Ne have synthesized novel chiralPolymedc catalysts containing cinchona squaramide moieties in the main chaln of the polymer by ADMETreaction. The ADMET polylnedzation reactions between the cinchona alkaloid・deHved squaralnide diene andHG2 Catalyst a丑'orded the chiral polymers. The chiral polylners were also used as catalysts in asylnmetricMichael addition reactions to give the products in good yields 、vith exce11ent stereoselectivities. They wereeasily recovered 丘'oln the reaction mixture and reused severaltimes.
Chapter 5 Presents the generalsumlnary ofthis whole thesis works.