Synthetic Utility of Fused-Cyclobutenes: Synthesis of Medium-Sized Cycloalkenes

therein.

(6)

(a) Clark, R. D.; Untch, K. G. J. Org. Chem. 1979, 44, 248. (b) Clark, R. D.; Untch, K.

G. J. Org. Chem. 1979, 44, 253. (c) Mislin, G.; Miesch, M. Eur. J. Org. Chem. 2001,

2001, 1753.

(7)

Ishihara, K.; Fushimi, M. J. Am. Chem. Soc. 2008, 130, 7532.

(8)

Kang, T.; Ge, S.; Lin, L. Lu, Y.; Feng, X. Angew. Chem. Int. Ed 2016, 55, 5541.

(9)

Schreyer, L.; Properzi, R.; List, B. IDPi Catalysis. Angew. Chem. Int. Ed. 2019, 58,

12761.

(10)

(a) Gatzenmeier, T.; Kaib, P. S. J.; Lingnau, J. B.; Goddard, R.; List, B. Angew. Chem.

Int. Ed. 2018, 57, 2464. (b) Gatzenmeier, T.; Turberg, M.; Yepes, D.; Xie, Y.; Neese, F.;

Bistoni, G.; List, B. J. Am. Chem. Soc. 2018, 140, 12671.

(11)

When the bulkier propiolate, i.e., ethyl propiolate 2b or isopropyl propiolate 2c, was

used to react with 3ca, the reaction became slower, resulting in lower yield than

propiolate 2a.

(12)

(a) Mayr, H.; Bug, T.; Gotta, M. F.; Hering, N.; Irrgang, B.; Janker, B.; Kempf, B.; Loos,

R.; Ofial, A. R.; Remennikov, G.; Schimmel, H. J. Am. Chem. Soc. 2001, 123, 9500. (b)

Mayr, H.; Kempf, B.; Ofial, A. R. Acc. Chem. Res. 2003, 36, 66.

(13)

(a) Inanaga, K.; Ogawa, Y.; Nagamoto, Y.; Daigaku, A.; Tokuyama, H.; Takemoto, Y.;

Takasu, K. Beilstein J. Org. Chem. 2012, 8, 658. (b) Kurahashi, K.; Yamaoka, Y.;

Takemoto, Y.; Takasu, K. React. Chem. Eng. 2018, 3, 626.

(14)

Bae, H. Y.; Höfler, D.; Kaib, P. S.; Kasaplar, P.; De, C. K.; Döhring, A.; Lee, S.;

Kaupmees, K.; Leito, I.; List, B. Nat. Chem. 2018, 10, 888.

99

(15)

Zhou, H.; Bae, H. Y.; Leutzsch, M.; Kennemur, J. L.; Bécart, D.; List, B. J. Am. Chem.

Soc. 2020, 142, 13695.

(16)

The author modified the BINOL

backbone of IDPi 1 to increase

acidity. However, the more electrondeficient BINOL dissociated from

imidodiphosphorimidate core even if

the desired catalyst was formed. In

terms

of

catalyst

stability,

the

modification of BINOL by the nitro group was successful; however, hardly soluble

properties and poor accessibility hampered further investigation.

(17)

Ito, T.; Takasu, K.; List. B. unpublished results. The representative result, see below.

The reaction conditions were carefully optimized using catalyst 13ub and ESE 17; the

yield and enantioselectivity eventually reached 90% and 78% ee, respectively. In recent

progress, newly designed catalysts with much higher acidity (not shown) have shown

better results, even with ESE 15g and 15h.

100

Publications

This study was published in or based on the following papers.

Related work

Synthesis of Dibenzoxazonines by Domino (2+2) Cycloaddition—4π Electrocyclic Ring

Opening Reaction of Cyclic Imines with Ynamides

Takasu, K.; Tsustumi, M.; Ito, T.; Takikawa, H.; Yamaoka, Y.

Heterocycles, 2020, 101, 423-428.

Chapter 1.

Synthesis of Functionalized Medium-Sized trans-Cycloalkenes by 4π Electrocyclic Ring

Opening–Alkylation Cascade

Ito, T.; Tsutsumi, M.; Yamada, K.; Takikawa, H.; Yamaoka, Y.; Takasu, K.

Angew. Chem. Int. Ed. 2019, 58, 11836-11840.

Chapter 2.

Synthesis of γ-Aryl Medium-sized Cyclic Enones by a domino 4π-Electrocyclic Reaction—

Heck–Matsuda Arylation Sequence at Ambient Temperature

Ito,T.; Takeuchi, N.; Yamaoka, Y.; Takikawa, H.; Takasu, K.

Synlett accepted manuscript

Chapter 3.

Ito, T.; Takasu, K.; List. B.

Unpublished results

101

Acknowledgements

First and foremost, the author is sincerely and extremely grateful to his supervisor,

Professor Kiyosei Takasu, for his invaluable advice, continuous encouragement, and patience

during his Ph.D. study. His unique ideas and ample experience have always inspired the author

during his academic research.

The author would like to express his sincere gratitude to Professor Ken-ichi Yamada

(Graduate School of Pharmaceutical Sciences, Tokushima University). His immense knowledge

and insatiable curiosity provided deep insights into the author's research.

The author would like to express his sincere and wholehearted appreciation to Dr. Hiroshi

Takikawa, and Dr. Yousuke Yamaoka (School of Pharmacy, Hyogo Medical University) for their

invaluable discussions, constructive advice, and constant encouragement throughout the author's

study.

The author is profoundly grateful to Professor Benjamin List (Max-Planck-Institut für

Kohlenforschung) for his professional guidance and constant encouragement, for allowing him

to study organocatalysis, and for giving the author a beautiful time at Mülheim an der Ruhr in

Germany. His passionate personality and attitude toward chemistry, both as a scientist and a

leader, profoundly influenced me.

The support and advice from Professor Yoshiji Takemoto (Graduate School of

Pharmaceutical Sciences, Kyoto University) and Professor Hirohisa Ohmiya (Graduate School

of Pharmaceutical Sciences, Kyoto University) are greatly appreciated.

The author also wishes to express his gratitude to all the colleagues and alums in the

Department of Synthetic Chemistry Laboratory (Graduate School of Pharmaceutical Sciences,

Kyoto University) for their valuable comments and for encouraging the author. The author

thanks Dr. Norihito Arichi (Graduate School of Pharmaceutical Sciences, Kyoto University) for

his pioneering work with cyclobutene chemistry in the author’s group and the first coaching.

The author would like to sincerely thank Dr. Yusuke Kuroda (Graduate School of

Pharmaceutical Sciences, Kyoto University), Dr. Bubwoong Kang (Graduate School of

Agricultural Science, Kobe University), and Dr. Shintaro Fujii for their coaching. The author is

grateful to Mr. Masaki Tsutsumi for his assistance with the experiments and to Dr. Kazuma

Shimoda and Dr. Naoki Ogawa for their invaluable discussion and encouragement in daily life.

The author would like to thank Dr. Keisuke Tomohara (Faculty of Arts and Science, Kyushu

University) for taking the author into academic life when the author was at the University of

Toyama as a graduate student. The author also thanks all the colleagues in the Department of

102

Hospital Pharmacy (University of Toyama), especially Dr. Takashi Ogihara and Dr. Kenta

Shinzawa for their encouragement in daily life.

The author would like to express his sincere gratitude to the secretaries in the Department of

Synthetic Chemistry Laboratory (Graduate School of Pharmaceutical Sciences, Kyoto

University) Rie Saruwatari and Mari Takada, and the secretaries in Max-Planck-Institut für

Kohlenforschung, Alexandra Kaltsidis, and all the staffs in the Elemental Analysis Center

(Kyoto University).

The author would like to thank all the colleagues at Max-Planck-Institut für

Kohlenforschung and Ono Pharmaceutical Co., Ltd..

The author would like to appreciate the financial support from the Japan Society for the

Promotion of Science (JSPS) and The Nagai Foundation Tokyo.

Lastly, the author is sincerely indebted to his parent, sister, and grandparents for

supporting and encouraging his academic research life for over nine years.

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