別紙4 (課程博士)
Date of submission

平成Departmcnt
StudentlD Numbel

年

7月日

14

第 D149402号

Environmental andLife sciences !学専1女
Pplicant's name

氏名29

Hamada shehataAwadMandour

Prof. Dr. seijilwasa
Supervjsors

ASSOC. prof. Dr

指導教員

Kazutaka shibatomi

Abstract

論文内容の要旨(博士)Iitle ofThesis

博士学位論文名

Novel catalytic Asymmetric carbene lransfer Reactions ofFunctionalized Diazo
Compoundswith olenns(官能基化ジアゾ化合物とオレフィンとの新規触媒的不斉カルベン移動反応)(Apptox.80o words)(要旨 1,200字程度)

Keywords: asymmetric synthesis, cyclopropanation, heterogeneous catalysis, water・solubleCatalysts.

Carbenes are very reactive species. The reactivity of a particular carbene depends on
the substituent groups. Their reactiV北y can be affected by metals. some of the reactions
Carbenes can do are insertions into c、H bonds, skeletal rearran曾ements, and additions todouble bonds through cyclopropanation reactions. chiral cyclopropane derivatives

areValuable structural motifs found in numerous natural products with diverse bi010牙icalactivities. Thus, during the past two decades, the development of synthetic method010gies
toward chiral cyclopropane compounds has attracted much attention and thetransition、metal、catalyzed asymmetric cyclopropanation of olefins W北h dia20acetates is

Widely rec0曾nlzed as one of the more powerful methods in terms of hi晉hly stereoselective
Synthesis.1n contrast to the exce11ent resU此S obtained with diazoacetates, diazoacetamides
are rarely used as a carbene source because of the low electrophilicity and steric hindrance ofthe resultin曾 metal、carbene intermediate. This prompted us to explore the asymmetric
Cyclopropanation of olefins with various diazoacetamides, namely, diazo X入7einreb amides,
because the resultin晉 Cyclopropanes are potentia11y useful synthetic intermediates that canbe easily converted to the correspondin套 aldehydes, ketones, and alchohols、

Chapter l Describes the importance of the carbene transfer reactions, especiaⅡy, theCyclopropanation reactions and the different strategies and types of catalysts have been also
i11Ustrated in this chapter.1n addition, a briefsummary of the most successful applications of
the or晉anometaⅡic catalysts over the past ten years was provided.

Chapter 2 ＼入le successfU11y developed of the first highly stereoselective cyclopropanation ofdiazo wienreb amides with olefins
Uslng
Chiral Ruql)・pheox'type catalysts.

Ruql)、Amm'pheox complex featurin牙 an internal quaternary ammonium unit exhibited
Obviously hi套her activity and enantioselectivity as compared W北h previously described

RU(11)、pheox complexs, to afford the corresponding chiralcyclopropylX入leinreb amides in hi曾hyields (up t099%) with exce11ent diastereoselectivities (up t099:1 dr) and enantioselectivities

(up t0 96% ee).1n addition, the use of acetoxy'functionalized diazoacetamide as a carbene
Source was found to be crucial for the high h'ans、selectivity of the cyclopropanation reaction
Moreover, the obtained chiral、入leinreb amides were readily converted to various useful
Synthetic intermediates, such as alcohols, ketones, and aldehydes, in one step and without
any loss of enantioselectivity.
Chapter 3 1n this chapter, we developed of the first highly stereoselective intramolecular
Cyclopropanation of h,ans・a11ylic diazo wienreb amides. After the investi牙ation ofmany chiral

Catalysts, Ruql)'Amm・pheox catalyst was proved to be the crucial catalyst for the highenantioselectivity for the cyclopropanation reaction. Moreover, the obtained chiral bicyclic
Compounds were readily converted to the corresponding ketone in one step and without any
10ss of enantioselectivity

Cbapter 4 Presents a water'soluble chiral RU(11)'Amm'pheox complex as a reusable andhighly enantioselective catalyst in intramolecular cyclopropanation of tl'ans、a11ylic diazo

Weinreb amides in a water/ether biphasic medium. X入le found that the RU(11)、Amm、pheox
Catalyst completely dissolved in water and completely undissolved in ether、 The reaction
Occurred at the interface snice the products mi曾rate to the ether、phase and the catalyst
return back to react with another molecule of tra刀S、a11ylic diazo weinreb amide. A variety ofRuqD・pheox catalysts with different functiona1 牙roups were screened and found that thefunctionality of the ruthenium catalyst with ammonium 宮roup is important to furnish theCyclopropanation product in hi套h yield. Different types of h'a刀S・a11ylic diazo weinreb amide
Were investi曾ated and afforded exce11ent reactivities up t099% yield and enantioselectivities
Up t0 99% ee. The easily separation of the ether・phase, which contains the cyclopropane
Product, a110ws the simple reuse of the catalyst in the water'phase at least six times withSli牙htly decrease in reactivity or enantioselectivity、

Chapter 5 Provides the experimental and analytical data for chapters from 2 t04

In summary, we have successfUⅡy designed and synthesized novel Ruql)、pheox type
Catalyst、 Th catalyst showed exce11ent reactivities and selectivities in carbene transfer
reactions. The catalyst had ability to be reused severaltimes and stored after reused without
10ss of its catalytic activity or selectivity.1n addition, no si曾nificant leaching of the catalysts
訊7asdetected. The Ruql)・Amln・pheox catalysts is expected to provide many further

Opportunities in asymmetric catalysis