別紙41 (課程博士(英文))Date of submission (month day, year)
Deparlmenl

Of

Dr. NaokiHaraguchi

Applied chemistry

Studen11D Number

and Life science

PP11Cant"s name

フ/5/2021

Dr. Kazutaka shibatomi

D 189403
Supervisors

SadiaAfrin chhanda

Abstract (Doctor)
Title ofThesis

Desi牙n and synthesis ofchiral hyperbranched polymers ofcinchona squaramides
and their application to asymmetric catalysis

Approx.80o words
The main objective of this tesearch is to study the in丑Uence of synthetic chiral polymers
in asymmetric feaction processes. chiral hyperbranched polymers (HBPS) of cinchona
Squaramides was synthesized for evaluatin牙 their catalytic performance in asymmetricSynthesis. For obtaining chiral hyperbranched polymers and linear polymers, the use ofCinchona alkaloids derivatives involves with the design sta晉e. Then, Mizor01くi・Heck (MH)Couplin曾 reaction and Yamamoto couplin号 reaction were used as synthetic method010gy to
Obtain the ch辻al hyperbranched polyme玲 and chⅡ'a11inear polymers respectively and finaⅡy,
the catalytic activity of chⅡ'al polymeric catalysts was assessed in asymmetric Michael
addition reactions. cinchona alkaloids and their derivatives have been widely employed as chiralOr套anocatalysts in diverse asyn〕n〕etric synthesis, because oftheir outstanding catalytic activity for
Several asymmetrlc reactions. Qulnlne, qulnldlne, clnchonldine and cinchonine are the major
Cinchona alkaloids which al'e comlnonly commerciaⅡy available. cinchona alkaloids are usefulfor
Suitable modifications to versatile catalysts il〕 asymmetric reactions due to their several
functionalities such as secondary alcoh01, quinoline ring, quinuclidine and viny1 牙1'OUP. Nthoughnumbers ofcinchona a11くaloid derivatives have been found in chiralorganocatalysts, their polymers
have not been synthesized. The polymeric catalyst design is an essentialtool to understand theefficient catalytic process in asymmetric transformations. several modifications have been alreadydone by different research groups and synthesis of many monomeric and dinleric organocatalysts
having cinchona squaramide moieties have also been Teported. The acidic NH ofthe squaramide
Can act as a H'bond donor, whereas the tertiary nitrogen of the quinuclidine ofcinchona alkaloids
may acts as both a H、bond acceptor and a base. SO, cinchona squaramide can act as a bifunctional
H、bonding or宮anocatalyst in the asymmetric synthesis. Thus, cinchona derived squaramides wereUsed for the desi牙n ofchiralpolymeric organocatalysts in this worlくCinchona derived squaramides have been proven as efficient or号anocatalysts in differentasymmetric transformations. Nthough several works have been reported with the10W'nlolecular'wei套ht squaramide catalysts derived from cinchona alkaloids,1ilnited number ofWorks have been carried out in the synthesis and application ofchiral polymeric organocatalyst on
the asymmetric transformation. cinchona squaramide polymeric catalysts can be prepared by theincorporation of low molecular wei曾ht dimeric squaramide, usin晉 Suitable polymerization

techniques under optimal reaction conditions.1n our previous reports, we have established MHPolymerization reaction which was a reliable c・c bond formin宮 reaction to synthesize chira11inear

Polym田.s from cinchona alkaloid derivatives.1n this work, we chose to synthesize chiral HBPS. wenoticed that this (MH) method010曾y is applicable toward the synthesis of chiral HBps fromCinchona a11くaloid derivatives. chiral HBps are highly branched tree・1ike three、dimensional
StructureS 訊7hich have drawn a lot of attention in various applications. chiral HBps containin牙Chiral catalytic moieties are potential polymer catalysts in asymmetrlc catalysis. cinchona、based
Chiral HBps have not been repoTted to date.1n this work, we designed and synthesized
Cinchona・based chiral HBps containing squaramide moiety by MH polym田'ization and anothernew coupling reaction which is caⅡed Yamamoto coupling and obtained polymers W田'e successfU11yapplied in the enantioselective Michael addition reactions.
The novel chiral cinchona squaramide HBps wa'e synthesized first by the reaction ofCinchona squaramide dimer and tri or tetrasubstituted arのれatic iodide via a MH polycondensation
reaction. The MH reactions occurred smoothly between the double bonds of the cinchona

Squaramide and aromatic tri・ 01' tetraiodides t0 曾ive chiral hyperbranched polymers. chiral HBPS
Were then applied in the asymmetric Michael addition reaction and exceⅡent enantioselectivity(>99% ee) was observed W北h 牙ood yield in the Michael addition reaction of β・ketoesters totra12gβ'nitrostyrene. Because ofinsolubility ofpolymeric catalysts in common or牙anic solvents, theHBps can be easily separated and reused up to six times W北houtlosing their catalytic activity andenantioselectivity. This is the first example of chiral HBp organocatalyst successfU11y applied tothe asymmetric Michael addition reaction.

Then the novel chiral HBps from cinchona squaramide containin牙 both vil〕yl (A) andiodophenyl(B)曾roups in AB2 and A9B type monome玲 Was designed and synthesized. These wereSuccessfuHy polymerized by the MH coupling reaction between the vlnyl and iodophenyl
functionaHtiesto give chiralHBPS. The chiralHBps prepared by one step MH polymerization were
Used as catalysts in asymmetric Michael reactions.1n case of the reaction between methyl
2'O×ocyclopentanecarbo>牙,1ate and h凌ns'β'nitrostyrene, the HBp catalysts showed high catalytic
activity with exceⅡent diastereoselectivity and enantioselectiV北y. Reactions between some other
Substrate combinations also occurred smoothly with the HBp catalysts.1nterestin容ly, the HBP
CatalystS 曾ave hi客her diastereoselectivity compared to that obtained with the low molecular weight
Catalyst. somewhat hi今her catalytic activity was also observed with HBp catalyst. precise contr01

Of the catalyst conformation may be possible in case of polymer catalyst. These results show thatthe design of chiral HBp catalyst may lead the development of M窒h・performance polymeric
Catalyst. The HBp catalysts were easily recovered from the reaction mixture and reused several
times without any decrease in catalytic activity and stereoselectivity.
After that the synthesis of cinchona squaramide'based chiral polyma's via the Yamamoto
Coupling reaction was described. Yamamoto couplin牙 reaction occurs between aromatic ha.1ides.
This couplin旦 reaction is nickel、catalyzed reaction of or牙anic halides in the presence of neutral
Iigands. Yamamoto couplin牙 reaction is advant且牙eous because only a single, hal0牙en・functionalized
monomer can be used to form polymer. X邸ith homopolymers, three copolymers were also
Synthesized from low molecular weight cinchona squaramide with achiral diiodo or dibromoaromatic compounds. chiral polymers were applied to the asymmetric Michael addition reactions
and afforded 牙ood to exceⅡent enantioselectiV北ies. The polymeric catalysts were recovered n.om
the reaction mixture and reused severaltimes without any decTease in catalytic activity.