Career-in-review Keiji Maruoka Reporter: Li Chen Supervisor: Prof. David Zhigang Wang

Introduction-Keiji Maruoka 2 Education B. S. Department of Industrial Chemistry, School of Engineering, Kyoto University 1976 Ph.D Department of Chemistry, University of Hawaii 1980 (with Prof. Hisashi Yamamoto) Professional Appointments Assistant Professor School of Engineering, Nagoya University Lecturer School of Engineering, Nagoya University Associate Professor School of Engineering, Nagoya University Professor Graduate School of Science, Hokkaido University Professor Graduate School of Science, Kyoto University and Hokkaido University 2001-present Professor Graduate School of Science, Kyoto University Prof. Keiji Maruoka

Research Career 3 Chiral Phase Transfer Catalysts Alkylations Enantioselective Synthesis of Amino Acids Other Alkylations N-Alkylations Asymmetric Conjugate Addition Asymmetric Amination Aldol Reaction Epoxidation Cyanation Chiral Organocatalysts Biaryl-Based Secondary Amine Catalysts Axially Chiral Dicarboxylic Acid Catalysts Bidentate Lewis Acid Catalysts

Research Career 4 Chiral Phase Transfer Catalysts Alkylations Enantioselective Synthesis of Amino Acids Other Alkylations N-Alkylations Asymmetric Conjugate Addition Asymmetric Amination Aldol Reaction Epoxidation Cyanation Chiral Organocatalysts Biaryl-Based Secondary Amine Catalysts Axially Chiral Dicarboxylic Acid Catalysts Bidentate Lewis Acid Catalysts

Chiral Phase Transfer Catalysts 5

General mechanism 6 T. Ooi, K. Maruoka, Angew. Chem. Int. Ed. 2007, 46, 4222.

Enantioselective Synthesis of α-Amino Acids 7 B. Lygo, P. G. Wainwright, Tetrahedron Lett. 1997, 38, 8595.

Enantioselective Synthesis of α-Amino Acids 8 T. Ooi, M. Kameda, K. Maruoka, J. Am. Chem. Soc. 1999, 121, 6519.

Enantioselective Synthesis of α-Amino Acids 9 T. Ooi, Y. Uematsu, M. Kameda, K. Maruoka, Angew. Chem. Int. Ed. 2002, 41, T. Ooi, Y. Uematsu, M. Kameda, K. Maruoka, Tetrahedron 2006, 62,

Enantioselective Synthesis of α-Amino Acids 10 M. Kitamura, Y. Arimura, S. Shirakawa, K. Maruoka, Tetrahedron Lett. 2008, 49, M. Kitamura, S. Shirakawa, Y. Arimura, X. Wang, K. Maruoka, Chem. Asian J. 2008, 3, 1702.

Enantioselective Synthesis of α-Amino Acids 11 M. Kitamura, Y. Arimura, S. Shirakawa, K. Maruoka, Tetrahedron Lett. 2008, 49, M. Kitamura, S. Shirakawa, Y. Arimura, X. Wang, K. Maruoka, Chem. Asian J. 2008, 3, 1702.

Asymmetric α,α-Dialkyl-α-Amino Acids Synthesis 12 T. Ooi, M. Takeuchi, M. Kameda, K. Maruoka, J. Am. Chem. Soc. 2000, 122, 5228.

Other Alkylations 13 T. Ooi, K. Fukumoto, K. Maruoka, Angew. Chem. Int. Ed. 2006, 45, 3839.

Other Alkylations 14 T. Hashimoto, K. Sakata, K. Maruoka, Angew. Chem. Int. Ed. 2009, 48, 5014.

N-Alkylations 15 S. Shirakawa, K. Liu, K. Maruoka, J. Am. Chem. Soc. 2012, 134, 916. >>

Asymmetric Conjugate Addition 16 R. He, C. Ding, K. Maruoka, Angew. Chem. Int. Ed. 2009, 48, 4559.

Asymmetric Conjugate Addition 17 R. He, S. Shirakawa, K. Maruoka, J. Am. Chem. Soc. 2009, 131,

Asymmetric Conjugate Addition 18 X.Wang,M. Kitamura, K. Maruoka, J. Am. Chem. Soc. 2007, 129, Q. Lan, X. Wang, K. Maruoka, Tetrahedron Lett. 2007, 48, 4675

Asymmetric Amination 19 R. He, X. Wang, T. Hashimoto, K. Maruoka, Angew. Chem. Int. Ed. 2008, 47, R.He, K. Maruoka, Synthesis 2009, 2289.

Asymmetric Amination 20 L. Wang, S. Shirakawa, K. Maruoka, Angew. Chem. Int. Ed. 2011, 50, 5327.

Aldol Reaction 21 T. Ooi, M. Taniguchi, M. Kameda, K. Maruoka, Angew. Chem. Int. Ed. 2002, 41, 4542.

Epoxidation 22 T. Ooi, M. Taniguchi, M. Kameda, K. Maruoka, Angew. Chem. Int. Ed. 2002, 41, T. Ooi, M. Kameda, M. Taniguchi, K. Maruoka, J. Am. Chem. Soc. 2004, 126, X-ray structure of 13-PF 6 (N, blue; O, red; PF 6, green)

Cyanation 23 T. Ooi, Y. Uematsu, K. Maruoka, J. Am. Chem. Soc. 2006, 128, T. Ooi, Y. Uematsu, J. Fujimoto, K. Fukumoto, K. Maruoka, Tetrahedron Lett. 2007, 48, 1337.

Research Career 24 Chiral Phase Transfer Catalysts Alkylations Enantioselective Synthesis of Amino Acids Other Alkylations N-Alkylations Asymmetric Conjugate Addition Asymmetric Amination Aldol Reaction Epoxidation Cyanation Chiral Organocatalysts Biaryl-Based Secondary Amine Catalysts Axially Chiral Dicarboxylic Acid Catalysts Bidentate Lewis Acid Catalysts

Chiral Secondary Amine Catalysts 25 T. Kano, K. Maruoka, Chem. Sci. 2013, 4, 907. Typical secondary amine catalysts derived from proline :

Biaryl-Based Secondary Amine Catalysts 26 T. Kano, K. Maruoka, Chem. Sci. 2013, 4, 907. Typical chiral biaryl-based secondary amine catalysts :

Aldol Reaction 27 T. Urushima, Y. Yasui, H. Ishikawa, Y. Hayashi, Org. Lett. 2010, 12, Anti-selective aldol reaction of glyoxylate :

Aldol Reaction 28 Anti-selective aldol reaction of glyoxylate : Syn-selective aldol reaction of glyoxylate and glyoxamide : T. Urushima, Y. Yasui, H. Ishikawa, Y. Hayashi, Org. Lett. 2010, 12, T. Kano, A. Noishiki, R. Sakamoto, K. Maruoka, Chem. Commun. 2011, 47,

Aldol Reaction 29 Anti-selective aldol reaction of glyoxylate : T. Urushima, Y. Yasui, H. Ishikawa, Y. Hayashi, Org. Lett. 2010, 12, T. Kano, A. Noishiki, R. Sakamoto, K. Maruoka, Chem. Commun. 2011, 47, Syn-selective aldol reaction of glyoxylate and glyoxamide :

Cross-Aldol Reaction 30 T. Kano, H. Sugimoto, K. Maruoka, J. Am. Chem. Soc. 2011, 133,

Mannich Reaction 31 J. W. Yang, C. Chandler, M. Stadler, D. Kampen, B. List, Nature, 2008, 452, 453. T. Kano, Y. Yamaguchi, K. Maruoka, Angew. Chem., Int. Ed., 2009, 48, Suppression of undesired aldol reactions :

Conjugate Addition 32 M. E. Kuehne, P. J. Reider, J. Org. Chem. 1985, 50, T. Kano, F. Shirozu, K. Tatsumi, Y. Kubota, K. Maruoka, Chem. Sci. 2011, 2, Suppression of catalyst consumption :

α-Hydroxyamination of Aldehydes 33 G. Zhong, Angew. Chem., Int. Ed. 2003, 42, T. Kano, M. Ueda, J. Takai, K. Maruoka, J. Am. Chem. Soc. 2006, 128, α-Hydroxyamination of aldehydes : α-Aminoxylation of aldehydes : Plausible transtion state models :

Research Career 34 Chiral Phase Transfer Catalysts Alkylations Enantioselective Synthesis of Amino Acids Other Alkylations N-Alkylations Asymmetric Conjugate Addition Asymmetric Amination Aldol Reaction Epoxidation Cyanation Chiral Organocatalysts Biaryl-Based Secondary Amine Catalysts Axially Chiral Dicarboxylic Acid Catalysts Bidentate Lewis Acid Catalysts

Axially Chiral Dicarboxylic Acid Catalysts 35 T. Hashimoto, K. Maruoka, J. Am. Chem. Soc. 2007, 129, Mannichi-type addition of diazo compounds : Locking the direction of the acidic OH group Establishing the efficient chiral environment

Axially Chiral Dicarboxylic Acid Catalysts 36 T. Hashimoto, N. Uchiyama, K. Maruoka, J. Am. Chem. Soc. 2008, 130, Trans-selective aziridination : Locking the direction of the acidic OH group Establishing the efficient chiral environment

Axially Chiral Dicarboxylic Acid Catalysts 37 T. Hashimoto, M. Hirose, K. Maruoka, J. Am. Chem. Soc. 2008, 130, Imino-azaenamine reaction : Locking the direction of the acidic OH group Establishing the efficient chiral environment

Research Career 38 Chiral Phase Transfer Catalysts Alkylations Enantioselective Synthesis of Amino Acids Other Alkylations N-Alkylations Asymmetric Conjugate Addition Asymmetric Amination Aldol Reaction Epoxidation Cyanation Chiral Organocatalysts Biaryl-Based Secondary Amine Catalysts Axially Chiral Dicarboxylic Acid Catalysts Bidentate Lewis Acid Catalysts

39 H. Hanawa, T. Hashimoto, K. Maruoka, J. Am. Chem. Soc. 2003, 125, Bis-Titanium Chiral Lewis Acid Catalyst :

Bidentate Lewis Acid Catalysts 40 H. Hanawa, T. Hashimoto, K. Maruoka, J. Am. Chem. Soc. 2003, 125, T. Kano, T. Hashimoto, K. Maruoka, J. Am. Chem. Soc. 2005, 127, Bis-Titanium Chiral Lewis Acid Catalyst :

Conclusion 41 By using "design of catalysts as artificial enzymes" and "environmentally-benign organic synthesis" as two important key-words, the synthetic organic chemistry laboratory focuses on the following topics: 1 Design of Chiral Phase Transfer Catalysts for Practical Amino Acid Synthesis 2 Design of Chiral Organocatalysts for Practical Asymmetric Synthesis 3 Development of Bidentate Lewis Acid Chemistry and Application to Selective Organic Synthesis

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