称号及び氏名

博士（理学）

Cartier Alex

学位授与の日付 令和 2 年 3 月 31 日
論文

名

論文審査委員Visible-light photoredox catalyzed multicomponent carbonylation ofalkyl radical precursors via the action of carbon monoxide ascarbonylative agent
可視光レドックス触媒による一酸化炭素をカルボニル源としたラジカル前駆体の多成分カルボニル化反応
主査
副査
副査
副査

福山 髙英
豊田 真弘
神川 憲
大橋 理人

CARTIER Alex, PhD candidate
Fukuyama Laboratory, OPU
Doctoral Thesis Abstract

Visible-light photoredox catalyzed multicomponent carbonylationof alkyl radical precursors via the action of carbon monoxide ascarbonylative agent
This thesis describes the development of novel photoredox catalyzed alkyl radical
carbonylation of organosilicates to form unsymmetrical ketones and aliphatic amides.
1. General Introduction to Photocatalyzed Carbonylation
CO is an abundant gas and is already widely used as a carbonylative agent in organic
chemistry. Historically, transition-metal catalyzed carbonylation has been the most intensively
studied method of carbonylation. But more recently, it has been discovered that CO is also
effective as a donor/acceptor-type radical C1 synthon that can be involved in radical
carbonylation chemistry. Thus, it was intensively studied by Ryu and coworkers to form avariety of carbonyl compound.1 On the other hand, visible-light photoredox catalysis has
experienced a significant increase of popularity among organic chemists during the last decade,as it often require very mild reaction conditions under visible light as energy source whileproviding as good results as more classic organic chemistry. However, until this day,photoredox catalyzed carbonylation syntheses were not yet extensively investigated and only
three groups published a result of photoredox catalyzed carbonylation of aryl diazonium salt
under photoreductive conditions (Scheme 1).2

Scheme 1. Photoreductive catalyzed carbonylations using diazonium salt as an aryl radical precursor.2

Meanwhile, new class of radical precursors were also investigated and recently, Fensterbank,
Ollivier and Goddard elaborated a new type of organosilicates compounds that promote alkyl
radicals under photooxidative conditions, even unstabilized primary alkyl radical, due to their
low oxidation potential (<1 eV vs. SCE).3 They showed that in the presence of an activatediridium photocatalyst through the illumination by blue LED lamp, radicals can be formed from

Doctoral Thesis Abstract

1

alkyl bis(catecholato)silicates and then trapped by an activated unsaturated double bond toperform an intermolecular addition (scheme 2).3
During my Ph-D course, I dedicated my time to expand the scope of photoredox
photocatalyzed carbonylative protocols for alkyl substrates. To obtain ultimately
unsymmetrical aliphatic ketones and aliphatic amides in mild conditions under blue LED light,
using original organosilicate radical precursors.

Scheme 2. Photooxidative catalyzed radical addition of organosilicate to radical acceptors3

2. Synthesis of Unsymmetrical Ketones through Photooxidative Carbonylation
Ryu and co-workers already reported a 3-component formation of
unsymmetrical ketones from alkyl halides, CO, and alkenes in thepresence of radical mediators.4 Alkyl bis(catecholato)silicates wereconsidered as alkyl radical precursors, for their convenience forlaboratory work and to avoid the use of any radical mediators. The
reaction of cyclohexylsilicate, CO, dimethyl maleate and a weak acidwas studied as a model (Scheme 3, eq 1). Optimized conditions wereobtained with organic dye 1,2,3,5‐tetrakis(carbazol‐9‐yl)‐4,6‐
dicyanobenzene 4CzIPN as photocatalyst.

4CzIPNA large scope of primary, secondary and tertiary silicates was tested, then many unsaturated
alkenes to in fine synthesize 20 unsymmetrical ketones, from 34% to 89% yield (Scheme 3, eq1).

Scheme 3. Synthesis of asymmetrical ketones under photooxidative conditions.

Doctoral Thesis Abstract2

In addition, carbonylative radical allylation was also supported by various silicates, giving
the desired product in moderate to good yield (Scheme 4, eq 2). This was the first example ofmetal-free oxidative photoredox catalysis, combined with radical carbonylation chemistry as
discussed in the chapter entitled Synthesis of Unsymmetrical Ketones through Photooxidative
Carbonylation.

Scheme 4. Carbonylative allylation under photooxidative conditions.

3. Synthesis of aliphatic amides through photooxidative carbonylation
Another photooxidative carbonylation reaction to form aliphatic amides was developed using
alkyl bis(catecholato)organosilicates as radical precursors, as well as 4CzIPN as photocatalyst,
an amine, and carbon tetrachloride CCl4 as radical mediator (Scheme 4, eq. 1). Literaturedescribed carbonylative synthesis of aliphatic amide in a radical/ionic system, in which an alkyl
iodide led to the alkyl radical and then to an acyl iodide intermediate. In that case, CCl4 wasadded to the mixture as a chlorine donor to form an in situ acyl chloride.5 A large scope ofsilicates and primary and secondary amine were tested, and 20 amides were obtained, from 31%
to 89% yield (Scheme 5, eq 3).

Scheme 5. Synthesis of aliphatic amides under photooxidative conditions.

Moreover, when the silicate is bearing an amine function, the intramolecular reaction occurs
smoothly, even when in competition with another amine, leading to formation of only one
product (eq 4).

Doctoral Thesis Abstract3

Carbonylation reactions are routinely carried out in batch reactor such as a stainless steel
autoclave, but a flow apparatus can also be used instead. Flow carbonylation present several
advantages over classic batch methods: high mass and energy transfer, and high gas-liquidinterfacial area. Therefore, carbonylation reaction can be carried out with a significantly
shortened reaction time and reduced amount of toxic CO gas in flow reactor.6 Flow version ofthis reaction presented huge potential, as excellent yields were obtained in much less time, only
5 min the whole under atmospheric pressure of CO (Scheme 6).

Scheme 6. Photoredox carbonylation under flow conditions.

In conclusion, multicomponent carbonylation reactions using alkyl substrates can be runsmoothly under photooxidative conditions, through the action of an inexpensive organic dye as
photocatalyst, excited by blue LED lamp. Various asymmetrical ketones and aliphatic amides
were synthesized in mild and metal-free conditions.

References:1) I. Ryu in Radicals in Organic Synthesis Vol. 2, (Eds. P. Renaud, M. P. Sibi), 2001, 22-43.
2) a) W. Guo, L.-Q. Lu, Y. Wang, Y. R. Wang, J.-R. Chen, W.-J. Xiao, Angew. Chem. Int. Ed.,
2015, 54, 2270; b) M. Majek, J. von Wangelin, Angew. Chem. Int. Ed., 2015, 54, 2270; c) L.
Gu, C. Jin, J. Liu, Green Chem., 2015, 17, 3733-3736.
3) V. Corcé, L.-A. Chamoreau, E. Derat, J.-P. Goddard, C. Ollivier, L. Fensterbank, Angew.
Chem. Int. Ed., 2015, 54, 11414.
4) I. Ryu, K. Nagahara, N. Kambe, N. Sonoda, S. Kreimerman, M. Komatsu, Chem. Commun.,
1998, 1953-1954.
5) a) R. E. Fostser, A. W. Larchar, R. D. Lipscomb, B. C. McKusick, J. Am. Chem. Soc. 1956,78, 5606-5611; b) D. Ginsburg, J. Am. Chem. Soc. 1951, 73, 702-704; c) T. Suzuki, J. Tsuji, J.
Org. Chem. 1970, 35, 2982-2986.
6) Fukuyama, T., Totoki, T., Ryu, I., Green Chem., 2014, 16, 2042-2050.

Doctoral Thesis Abstract4

List of publications:
1) A. Cartier, E. Levernier, V. Corcé, A.-L. Dhimane, T. Fukuyama, C. Ollivier, I. Ryu, L.
Fensterbank, Angew. Chem. Int. Ed., 58, 1789-1793 (2019).
2) A. Cartier, E. Levernier, A.-L. Dhimane, M. Zhang, S. Ognier, M. Tatoulian, T. Fukuyama,
C. Ollivier, I. Ryu, L. Fensterbank, Submitted (2020).

Conference proceedings:
A. Cartier, E. Levernier, V. Corcé, A.-L. Dhimane, T. Fukuyama, C. Ollivier, I. Ryu, L.
Fensterbank, Carbonylation of Alkyl Radicals Derived from Organosilicates through VisibleLight Photoredox Catalysis. The 98th CSJ Annual Meeting, 2018, 7 min oral presentation.

Doctoral Thesis Abstract5

学位論文審査結果の要旨
近年、可視光を用いた光レドックス触媒を用いた分子変換反応の開発が多くの研究グループにより精力的になされている。一方、一酸化炭素は有用な C１ユニットであり、各種カルボニル化合物の合成に広く用いられてきたが、光レドックス触媒を用いたカルボニル化反応の開発はほとんど進んでおらず、これまでに数例が報告されているのみである。これらの報告例は、芳香族ジアゾニウム塩を基質とした基質への１電子還元を鍵とする反応であり、基質への１電子酸化を鍵とする光レドックス触媒によるカルボニル化はこれまでに報告例はない。本論文では、光レドックス触媒存在下、有機シリケートを基質として用いることにより１電子酸化を鍵としたカルボニル化反応について検討している。
論文の内容は以下の通りである。
(1) 有機シリケートを基質とし、一酸化炭素、電子欠損オレフィンとの３成分連結反応により非対称ケトンの合成を行っている。本反応では、光レドックス触媒として安価に調製可能な有機色素を用いることで遷移金属錯体非存在下でのカルボニル化を実現している。ラジカルアクセプターとして-不飽和カルボニル化合物を用いると非対称ジアルキルケトンが得られ、ラジカルアクセプターとしてアリルスルホンを用いると、ラジカルの付加脱離を経てアルキルアリルケトンが良好な収率で得られることを見出している。また、反応機構に関する検討も十分になされ、本反応が、励起された光触媒からの１電子酸化を鍵としていることを明らかとしている。１電子酸化を鍵とした光レドックス触媒によるカルボニル化は、本手法が初めての例である。
(2) 有機シリケートと一酸化炭素、アミンとの３成分反応によりアミドが良好な収率で得られることを見出している。本反応では四塩化炭素の添加が有効であるが、系中で生成したアシルラジカルの四塩化炭素からの塩素引き抜きにより酸塩化物が生成していることを提唱し、その生成を実験的に確認している。また、分子内にアミノ基を有するシリケートを用いると分子内環化が進行しラクタムが良好な収率で得られることも見出している。本反応は耐圧性のステンレス製反応容器内で実施されるが、８０気圧の一酸化炭素が必要であり、数十時間の反応時間を要した。これらの問題を解決するた
めに光照射効率に優れたフロー型反応装置を用いたフローカルボニル化を検討している。また、フロー系での気—液異相系は気液接触面積が増大することからも反応の効率化が期待できる。検討の結果、１気圧の一酸化炭素存在下、わずか 5 分で反応が完結することを見出し、反応効率を飛躍的に改善することに成功している。
以上のように本論文では、光レドックス触媒を用いた一電子酸化を鍵とする新規カルボニル化反応の開発に成功している。いずれの反応も合成化学的に有用である。本委員会は本論文の審査、最終試
験の結果に基づき、Alex Cartier 氏に博士（理学）の学位を授与することを適当と認める。
学位論文審査委員会

委員長

福山 高英
豊田 真弘
神川 憲
大橋 理人