RESEARCH ACTIVITIESDesign and Synthesis of Chiral Organic
Molecules for Asymmetric Synthesis
Department of Life and Coordination-Complex Molecular Science
Division of Complex Catalysis

MemberSecretary
WATANABE, Yoko

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

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,

7212882–12883 (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
selective Diels–Alder Reaction of α,β-Unsaturated Aldehydes withAmidodienes,” J. Am. Chem. Soc. 133, 19294–19297 (2011).

Annual Review 2014

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.

Figure 2. 1,3-Alkyl migration of 1-substituted-3-buten-1-amine. a)
Our discovery, b) Previous report by Ollis et al.

activity was served by the electronic effect at the CNaph(3’)–
CAr(3), and (iii) the precise distinction of asymmetric reaction
space was realized by the different substitution at the CNaph(3)–CAr(3) and the CNaph(3’)–CAr(3).

Figure 3. Molecular design of chiral C1 symmetric bis-phosphoric acid.

3. Halogen Bond Donor Catalyzed
Allylation Reaction of Isoquinoline 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 or aryl
substituents. We recently developed synthetic methodology for
perfluorinated aryl compounds, and applied it for the develop­
ment of chiral Brønsted acid catalysts. On the basis of ourachievements, we have examined it to develop halogen bonddonor catalyzed allylation reaction.
We found that pentafluoroiodebenzene was able to cata­lyze the allylation reaction of isoquinoline with allylsilatrane
to give the corresponding product in good yield.5)

2. Design of C1 Symmetric Chiral BisPhosphoric Acid: Catalytic Enantio­
selective Diels–Alder Reaction of Acroleinwith Amidodienes
We recently developed (R)-3,3’-di(2-hydroxy- 3-aryl­phenyl)
binaphthol derived pseudo-C2 symmetric chiral bis-phosphoricacid which efficiently catalyzed enantioselective Diels–Alderreaction of α,β-unsaturated aldehydes with amido­dienes.3) Two
cyclic phosphoric acid motifs introduced between the CNaph(2)and CAr(2) positions and between the CNaph(2’) and CAr(2)positions represents a characteristic feature of our catalysts. On
the basis of our early hypothesis and recent results, the intra­
molecular hydrogen bonding between two acidic moieties seems
to be deeply related to control an atropisomeric behavior ofcatalyst structure; however, none of systematic study have beenemployed with respect to the importance of hydrogen bond in
the molecular design of chiral catalysts.
We designed a new C1 symmetric chiral bis-phosphoricacid that possesses an electron-withdrawing group at theC Naph(3’)–C Ar(3), C Ar(5). 4) We found that (i) the stereo­
dynamic behavior of atropisomeric biaryls was controlled by
the intervention of hydrogen bond, (ii) the requisite catalyst

Figure 4. Halogen bond donor catalyzed allylation reaction. Com­
parison with Brønsted acid/hydrogen bond donor catalyst.

References
1) N. Momiyama, C. Kanai, A. Takei and M. Terada, Manuscript inpreparation.
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, T. Konno, Y. Furiya, T. Iwamoto and M. Terada, J.
Am. Chem. Soc. 133, 19294–19297 (2011).
4) N. Momiyama, K. Funayama, H. Noda, M. Yamanaka, N. Akasaka,
S. Ishida, T. Iwamoto and M. Terada, Manuscript in preparation.
5) N. Momiyama, H. Nishimoto, Y. Kamata and M. Terada,Manuscript in preparation.

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