別紙41 (課程博士(英文))Date ofsubmission (month daDepadmentear)0ν 08 / 2019

SEU11WASA

Environmental and Life

StudenuD Number

159402

SciencesSupervisors

KAZUTAKASHIBATOMILETHILOANCHI

Pplicant's name

Abstract (Doctor)
Catalytic Asymmetric cyclopropanations ofDiazo phosphonates and Designed Diazo
Ketones
Iitle ofThesis(ジアゾリン酸エステルとデザインジアゾケトンの触媒的不斉シクロプロパン化反応)

Approx.80o words
The cyclopropane subunit is present in many bi010gica11y impodant compounds induding terpenes,
Pheromones, fatty acid metabolites, and unusual amino acids, and it sho、Ns a large spectrum of bi010gical
Properties, including en勾,me inhibition and insecticidal, antifungal, herbicidal, antimicrobial, antibiotic,antibacterial, antitumor, and antiviral activities. This fact has inspired chemists to and novel and diverse
approaches to their synthesis, and thousands ofcyclopropane compounds have been prepared.1n particular,
natura11y occurring cyclopropanes bearing simple or complex functionalities are chiral compounds; thus,
the cyclopropane motif has long been established as a valuable platform for the development of new
asymmetric techn010gies. Asymmetric synthesis constitutes the main strategy to gain access toenantioenriched compounds, involving the use of either chiral auxiliaries or catalysts that in tum can be
metal‑centered, smaⅡ organic asymmetric molecules or enzymes. New and more ef5Cient methods
employing a11 these method010gies to gain enarltiomerica11y enriched cyclopropanes are sti11 evolving.
Transition metal‑catalyzed cyclopropanation involving carbene intermediate is powerful and useful
methods for constructing important substruC加res of targeted molecules, and therefore they have been
extensively studied for the past couple ofdecades.
Although Ruthenium complex is newcomer in the field ofcatalytic cyclopropanation,it has emerged as
the third important catalyst metal for the C雛benoid chemistry of diazo compounds, besides copper andrhodium. Therefore, future developments should try to find catalysts that give ruthenium carbene
intermediates electrophilic enough to react with a wide range of oleanic substrates and that at the sametime give high levels of dia・ and enantioselectivity. This prompted us to explore the asymmetric
Cyclopropanation of various diazo compounds 、Nhich are potentia11y building blocks and expectant to beapplied in pharmaceutical and medicinal aelds.

Chapter l. Describes the history of the carbene transfer reactions. A brief review of the mostSuccessful metal carbene inte姉ediates in asymmetric cyclopropanations over the past ten years areProvided. Furthermore, the application of metal carbene complexes in the synthesis of bi010gica11y・active

Or natural product・1ike compounds are also mentioned.
Chapter 2. Recendy, our research group reported thatthe complex, RUσ1)・pheox, has been completely
efacient in carbene transfer reactions, particularly the cyclopropanation of diethyl

diazomethylphosphonates with various electron・deacient olefins such as a,β・unsaturated carbonylCompounds or vinyl carbamates in exce11ent yields and 、Nith high enantioselectiviw. Thus, here in, novel
Catalysis involving phosphonomethylation of N・methylaniline and asymmetric cydopropyゆhosphonation
reactions of NN・diethylaniline derivatives 、Nith diazomethylphosphonates are reported. optica11y active
Cyclopropyゆhosphonate derivatives^ere

directly synthesized from diazomethyゆhosphonates andNN・diethylaniline derivatives catalyzed by a 3,4,5 methoxy・RU(1D・pheox complex in one step in goodyields and high diastereoselectivities (up to trans/cis => 99:1<) and enantioselectivities (up t099% ee). D
Iabeling mechanistic studies of phosphonomethylation and cyclopropyゆhosphonation suggested that an
enamine or iminium intermediate 、Nas generated in the reaction process.

Chapter 3. continuously, the 3,4,5 methoxy・RU(11)・pheox・catalyzed cyclopropanation ofstyrene with
diacceptor diazo compound is initiaⅡy repoHed in 加e corresponding cyclopropylphosphonate product in
exce11ent yield (up t0999'、0) and good enantioselectivity (up t068% ee).

Chapter 4. FUHhermore, finding catalysts 、Nhich can cyclopropanate with various diazo compounds toenrich stereoselectivity also have been developed during the last decades.1n our previous researches,
RU(1D‑pheox‑catalyzed asymmetric cyclopropanation ofsuccinimidyl diazoacetate with olefins and a11enes
resulted in high yields and exce11ent enantioselectivities and of a,β・unsaturated carbonyl compounds withacetonyl diazoacetate in much higher stereoselectivities (diastereoselectivity >99:1 and enantioselectivity
Up t099%). consequently, herein, The diazo derivative ofacetonyl acetate is a useful basic skeleton for theSynthesis of cyclopropyl ketones.1he intermolecular cyclopropanations of diazo acetoxy acetone with
Olefins are accomplished by using a novelp・nitro・RU(11)‑dゆhenyl・pheox catalystto give the corresponding
Optica11y active cyclopropane derivatives in good yields (up t0 95%)、Nith exce11ent diastereoselectivities(up t099:1) and enantioselectivities (up t098% ee).
Chapter 5. Fina11y, aⅡ the experimental and a11alytical data as the evidence for chapter 2 t0 4 aredescribed.

In summary, the RU(1D‑pheox catalyzed asymmetric cyclopropanation reaction proved to be anefficient and straighげorward method for the preparation of chiral cydopropylphosphonation, diaceptor
Cyclopropylphosphonates, ketone cyclopropanes,、Nhich are important intermediates in the synthesis ofmany bi010gica11y active compounds.、Ne believe that RUσD‑pheoxderivatives wiⅡ Contribute to theProgress ofnot only asymmetric cyclopropanation but also other asymmetric carbene transferreactions.
List ofpublications and experimentalsuppoding information are induded in the appendices.