RESEARCH ACTIVITIESDesign and Synthesis of Chiral Organic
Molecules for Asymmetric Synthesis
Department of Life and Coordination-Complex Molecular Science
Division of Complex Catalysis
Education2000 B.S. Nagoya University
2005 Ph.D. The University of Chicago
Professional Employment
2005 Postdoctoral Fellow, Harvard University
2006 Assistant Professor, Tohoku University
2014 Associate Professor, Institute for Molecular Science
Associate Professor, The Graduate University for Advanced
Studies

MOMIYAMA, Norie
Associate Professor[momiyama@ims.ac.jp]

KeywordsAwards
2003 The Elizabeth R. Norton Prize for Excellence in Research in
Chemistry, University of Chicago
2004 Abbott Laboratories Graduate Fellowship2005 Damon Runyon Cancer Research Foundation Post Doctoral
Research Fellowship2008 Thieme Chemistry Journals Award
2014 The 17th Morita Science Research Award
Central Glass Co., Ltd. Award in Organic Chemistry, Japan

MemberAssistant Professor
OHTSUKA, Naoya
Graduate Student
HORI, Tatsuaki
OISHI, Shunya
KATO, Masayuki
Technical Fellow
NISHIOKA, Yukina
HARADA, Kuniko
KAKINUMA, Shuya
Secretary
USHIDA, Hinano

Synthetic Chemistry, Molecular Catalyst, Non-Covalent Interaction

The field of molecular catalysis has been an attractive areaof research to realize efficient and new transformations in thesynthesis of functional molecules. The design of ligands andchiral molecular catalysts has been recognized as one of themost valuable strategies; therefore, a great deal of effort has
been dedicated to the developments. In general, “metal” hasbeen frequently used as the activation center, and conformationally rigid catalyst framework has been preferably components for the catalyst design. To develop new type of molecular catalysis, we have focused on the use of hydrogen andhalogen atom as activation unit, and have utilized non-covalentinteractions as organizing forces of catalyst framework in themolecular design of catalyst, which had not received muchattention until recently. We hope that our approach will open
the new frontier in chiral organic molecules from chiral molecular chemistry to chiral molecular science.

Figure 1. Hydrogen bonding network in chiral bis-phosphoric acidcatalyst derived from (R)-3,3’-di(2-hydroxy-3 -arylphenyl)binaphthol.
Hydrogen bond acts as activation unit for the substrate in asymmetric
reaction space and controls atropisomeric behavior in naphthyl–phenyl axis.

Selected Publications• T. P. Yoon and E. N. Jacobsen, Science 299, 1691–1693 (2003).
• N. Momiyama and H. Yamamoto, “Brønsted Acid Catalysis ofAchiral Enamine for Regio- and Enantioselective Nitroso AldolSynthesis,” J. Am. Chem. Soc. 127, 1080–1081 (2005).
• N. Momiyama, H. Tabuse and M. Terada, “Chiral Phosphoric AcidGoverned Anti-Diastereoselective and Enantioselective HeteroDiels–Alder Reaction of Glyoxylate,” J. Am. Chem. Soc. 131,12882–12883 (2009).
• N. Momiyama, T. Konno, Y. Furiya, T. Iwamoto and M. Terada,“Design of Chiral Bis-Phosphoric Acid Catalyst Derived from(R)-3,3’-Di(2-hydroxy-3-arylphenyl)binaphthol: Catalytic Enantio-66

selective Diels–Alder Reaction of α,β-Unsaturated Aldehydes withAmidodienes,” J. Am. Chem. Soc. 133, 19294–19297 (2011).
• N. Momiyama, H. Tabuse, H. Noda, M. Yamanaka, T. Fujinami, K.
Yamanishi, A. Izumiseki, K. Funayama, F. Egawa, S. Okada, H.
Adachi and M. Terada, “Molecular Design of a Chiral Brønsted
Acid with Two Different Acidic Sites: Regio-, Diastereo-, andEnantioselective Hetero-Diels–Alder Reaction of Azopyridinecarboxylate with Amidodienes Catalyzed by Chiral Carboxylic
Acid–Monophosphoric Acid,” J. Am. Chem. Soc. 138, 11353–11359 (2016).

Annual Review 2022

1. Design of Hydrogen Bond-Based
Molecular Catalysts
Allylation of imines with allylic metal reagents has been
one of the most valuable tools to synthesize enantioenrichedhomoallylic amines. Due to the inherent nature of allylic metal
reagent, however, regioselectivity has been a long-standing
subject in this area. To develop the synthetic reaction forenantioenriched linear homoallylic amines, we discoveredchirality transferred formal 1,3-rearrangement of ene-aldiminesin the presence of Brønsted acid, and developed it as synthetic
method for variety of enantioenriched linear homo allylicamines.1) Furthermore, we studied details of reaction mechanism and succeeded catalytic asymmetric version of thisrearrangement.2) On the basis of our discovery, catalytic asymmetric version of this reaction was developed.3) To the best
our knowledge, our discovery is the first example of catalytic
asymmetric methylene migration.

that strong halogen bonds are realized when “R” is highlyelectronegative substituents such as perfluorinated alkyl oraryl substituents. On the basis of electrophilic feature for
halogen atom, we have examined it to develop catalysis withhalogen bond for carbon–carbon bond forming reactions.9,10)
We found that perfluorinated iodoaryls are able to catalyze
the allylation reaction to N-activated heteroaromatics. On thebasis of this discovery, a quantitative approach was studied
using 4-substituted perfluorinated iodobenzene.11) Examination of the electrostatic potential surfaces showed that
substituent R groups significantly affected the charge densityof iodine, fluorine, and carbon on the benzene ring. 19F NMR
titrations were used to determine the binding constants K forchloride, and their catalytic activities were evaluated in theallylation reaction. We revealed that the log K and productyields were linearly correlated, and that they were dependent
on the Hammett substituent parameter, σ meta. This linear
correlation provided a quantitative predictive model for boththe binding constant and the reaction yield. Concomitantly,
this efficiently permitted the development of a highly active
anion-binding catalyst, namely 4-CNC6F 4I. The catalytic
activity of 4-CNC6F4I was established in the allylation andcrotylation of silatrane reagents to N-activated isoquinolines.

Figure 2. Asymmetric counteranion-directed catalysis via OH···O,CH···O, CH···π, π···π interactions.

Perfluorinated aryls have emerged as an exquisite class ofmotifs in the design of molecular catalysts, and their electronicand steric alterations lead to notable changes in the chemicalyields and the stereoselectivities. We developed the perfluoaryls-incorporated chiral mono-phosphoric acids as chiral
Brønsted acid catalysts that can deliver high yields and stereoselectivities in the reactions of imines with unactivated alkenes.
We have described the first example of a diastereo- andenantioselective [4+2] cycloaddition reaction of N-benzoyl
imines, as well as the enantioselective three-component imino–
ene reaction using aldehydes and FmocNH2.4)
We have developed (R)-3,3’-di(2-hydroxy- 3-arylphenyl)
binaphthol derived chiral bis-phosphoric acid which efficiently
catalyzed enantioselective Diels–Alder reaction of acroleins
with amidodienes.5,6) We demonstrated that two phosphoricacid groups with individually different acidities can play
distinct roles in catalyst behavior through hydrogen bonding
interactions. Therefore, we developed a Brønsted acid withtwo different acidic sites, aryl phosphinic acid-phosphoricacid.7) Furthermore, molecular design of a chiral Brønstedacid with two different acidic sites, chiral carboxylic acid–cyclic mono-phosphoric acid, was identified as a new andeffective concept in asymmetric hetero-Diels–Alder reactionof 2-azopyridinoester with amidodienes.8)

2. Design of Halogen Bond-Based
Molecular Catalysts
Halogen bonds are attractive non-covalent interactions
between terminal halogen atoms in compounds of the type
R—X (X = Cl, Br, I) and Lewis bases LBs. It has been known

Figure 3. Molecular electrostatic potential surfaces of 4-RC6F4I (R: CH3,H, F, and CF3) at the M06-2X-D3/6-311+G(d,p)-SDD level of theory.

References
1) C. Jongwohan, Y. Honda, T. Suzuki, T. Fujinami, K. Adachi and N.
Momiyama, Org. Lett. 21, 4991–4995 (2019).
2) N. Momiyama, Y. Honda, T. Suzuki and C. Jongwohan, Asian J.
Org. Chem. 10, 2205–2212 (2021). [Invitation only, special collection on the Topic of Organocatalysis]
3) N. Momiyama, A. C. Jongwohan, N. Ohtsuka, P. Chaibuth, T.
Fujinami, K. Adachi and T. Suzuki, J. Org. Chem. 87, 9399–9407(2022).
4) N. Momiyama, H. Okamoto, J. Kikuchi, T. Korenaga and M.
Terada, ACS Catal. 6, 1198–1204 (2016).
5) N. Momiyama, T. Konno, Y. Furiya, T. Iwamoto and M. Terada, J.
Am. Chem. Soc. 133, 19294–19297 (2011).
6) N. Momiyama, K. Funayama, H. Noda, M. Yamanaka, N. Akasaka,S. Ishida, T. Iwamoto and M. Terada, ACS Catal. 6, 949–956(2016).
7) N. Momiyama, T. Narumi and M. Terada, Chem. Commun. 51,16976–16979 (2015).
8) N. Momiyama, H. Tabuse, H. Noda, M. Yamanaka, T. Fujinami, K.
Yamanishi, A. Izumiseki, K. Funayama, F. Egawa, S. Okada, H.
Adachi and M. Terada, J. Am. Chem. Soc. 138, 11353–11359 (2016).
9) N. Momiyama et al., ChemRxiv DOI: 10.26434/chemrxiv-20221ljk9-v4 (2022).
10) N. Momiyama et al., One. article under revision; six manuscripts
under preparation for submission.
11) N. Momiyama, A. Izumiseki and N. Ohtsuka, ChemPlusChem 6,913–919 (2021). [Invitation only, special issue for ISXB-4]

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