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
IZUMISEKI, Atsuto
Post-Doctoral Fellow
FUJINAMI, Takeshi
YAMANISHI, Katsunori
YOSHIZAWA, Akina
Graduate Student
JONGWOHAN, Chanantida
NAKASHIMA, Fumio
WATANABE, Taku
MASUI, Yu
Technical Fellow
TSUKAHARA, Shiori
Secretary
WATANABE, Yoko

Organic Synthesis, 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, and C2- or pseudo C2 symmetry has been
preferably components for the catalyst design. To develop new
type of molecular catalysis, we have focused on the use ofhydrogen and halogen atom as activation unit, and have
utilized conformationally flexible components in the molecu­
lar design of catalyst, which had not received much attention
until recently. We hope that our approach will open the newfrontier in chiral organic molecules from chiral molecularchemistry 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–phenylaxis.

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 Aldol
Synthesis,” 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 2017

1. Brønsted Acid Catalyzed Asymmetric
1,3-Alkyl Migration of 1,2,2-Substituted
Butenyl Amines: Asymmetric Synthesis ofLinear Homoprenylamines
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 homoprenylic amines, we discoveredchirality transferred 1,3-alkyl migration of 1,2,2-substituted
butenyl amines in the presence of trifluoromethyl acetic acid,and developed it as synthetic method for variety of enantio­
enriched linear homoprenylic amines.1) In sharp contrast, Olliset al. previously reported that chirality was significantly
dropped in 1,3-alkyl migration of N,N-dimethyl-1-substituted3-buten-1-amine.2) To the best our knowledge, our discovery is
the first example of chirality transferred 1,3-alkyl migrationand the new entry of the synthetic methodology for the linear
enantioenriched homoallylic amines.

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. However, unfortunately, thedistinctive potential of perfluorinated aryls has not been fully
exploited as design tools in the development of chiral Brønstedacid catalysts. We developed the perfluoaryls-incorporated
chiral mono-phosphoric acids as chiral Brønsted acid catalysts
that can deriver high yields and stereoselectivities in thereactions of imines with unactivated alkenes. We have described
the first example of a diastereo- and enantioselective [4+2]cycloaddition reaction of N-benzoyl imines, as well as theenantioselective three-component imino–ene reaction using
aldehydes and FmocNH2.3)
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.4,5) We demonstrated that two phosphoricacid groups with individually different acidities can play
distinct roles in catalyst behavior through hydrogen bonding
interactions. Hence, we were interested to explore whether acombination of different acidic functional groups, in particular
an aryl phosphinic acid-phosphoric acid, would function as anefficient Brønsted acid catalyst. We developed a Brønsted acidwith two different acidic sites, aryl phosphinic acid-phosphoricacid, and its catalytic performance was assessed in the heteroDiels–Alder reaction of aldehyde hydrates with Danishefsky’s
diene, achieving high reaction efficiency. 6) Furthermore,

molecular design of a chiral Brønsted acid with two different
acidic sites, chiral carboxylic acid–cyclic mono-phosphoricacid, was identified as a new and effective concept in asym­
metric hetero-Diels–Alder reaction of 2-azopyridinoester withamidodienes.7)

Figure 2. Chiral carboxylic acid–phosphoric acid-catalyzed azohetero-Diels–Alder reaction.

3. Halogen Bond Donor Catalyzed Reactionof N-Heteroaromatics with Allylsilatrane
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 LB. It has been known
that strong halogen bonds are realized when “R” is highly
electronegative substituents such as perfluorinated alkyl oraryl substituents. We recently developed synthetic method­
ology for perfluorinated aryl compounds, and applied it for thedevelop­ment of chiral Brønsted acid catalysts. On the basis ofour achievements, we have examined it to develop halogen
bond donor catalyzed allylation reaction.
We found that pentafluoroiodebenzene was able to cata­lyze the allylation reaction of isoquinolines, quinolones, andpyridines with allylsilatrane, crotylsilatrane, and prenyl silatrane
to give the corresponding product in good yield.8)

References
1) N. Momiyama et al., Manuscript in preparation.
2) R. W. Jemison, T. Laird, W. D. Ollis and I. O. Sutherland, J. Chem.
Soc. Perkin Trans. 1 1458–1461 (1980).
3) N. Momiyama, H. Okamoto, J. Kikuchi, T. Korenaga and M.
Terada, ACS Catal. 6, 1198–1204 (2016).
4) N. Momiyama, T. Konno, Y. Furiya, T. Iwamoto and M. Terada, J.
Am. Chem. Soc. 133, 19294–19297 (2011).
5) N. Momiyama, K. Funayama, H. Noda, M. Yamanaka, N. Akasaka,
S. Ishida, T. Iwamoto and M. Terada, ACS Catal. 6, 949–956(2016).
6) N. Momiyama, T. Narumi and M. Terada, Chem. Commun. 51,16976–16979 (2015).
7) 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).
8) N. Momiyama et al., under revision for resubmission.

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