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
Post-Doctoral Fellow
FUJINAMI, Takeshi
Graduate Student
HORI, Tatsuaki
OISHI, Shunya
KATO, Masayuki
KOTANI, Shunsuke
Technical Fellow
NISHIOKA, Yukina
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 confor­
mationally rigid catalyst framework has been preferably com­ponents for the catalyst design. To develop new type of molecu­
lar 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 molecu­
lar 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

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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 2021

1. Brønsted Acid Catalyzed AsymmetricRearrangement: Asymmetric Synthesis ofLinear Homoallylic Amines
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 homo­a llylicamines.1) Furthermore, we studied details of reaction mecha­
nism and succeeded catalytic asymmetric version of thisrearrangement.2) On the basis of this study, catalytic asym­
metric version of this reaction was developed.3) To the best
our knowledge, our discovery is the first example of catalyticasymmetric methylene migration.

2. Design of Chiral Brønsted Acid Catalyst
Chiral Brønsted acid catalysis has been recognized as oneof the useful tools in asymmetric synthesis. We have contrib­
uted to this area by focusing on the use of perfluoroaryls andC1-symmetric design.
Perfluorinated aryls have emerged as an exquisite class of
motifs in the design of molecular catalysts, and their electronicand steric alterations lead to notable changes in the chemicalyields and the stereoselectivities. We developed the perfluo­
aryls-incorporated chiral mono-phosphoric acids as chiral
Brønsted acid catalysts that can deriver high yields and stereo­
selectivities 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)

3. Design of Catalysis with Halogen Bondfor Carbon–Carbon Bond Forming Reactions
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

that strong halogen bonds are realized when “R” is highly
electronegative substituents such as perfluorinated alkyl or
aryl substituents. We recently developed synthetic metho­
dology for perfluorinated aryl compounds and applied it forthe development of chiral Brønsted acid catalysts. On the basisof our achievements, we have examined it to develop catalysiswith halogen bond for carbon–carbon bond forming reactions.9)
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. 10) Exami­
nation 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. 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] doi: 10.1002/ajoc.202100302
3) N. Momiyama et al., submitted.
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., Two communications & Two articles underrevision; five manuscripts under preparation for submission.
10) N. Momiyama, A. Izumiseki and N. Ohtsuka, ChemPlusChem 6,913–919 (2021). [Invitation only, special issue for ISXB-4]

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