Life science
Pharmaceuticals, Agrochemicals, Functional chemicals

Synthetic organic chemistry using solid catalysts withnanosized pores
Synthetic Medical Chemistry, Graduate School of Pharmaceutical Sciences
Professor Shuji Akai

Researchmap https://researchmap.jp/shuji_akai

Assistant Professor Kyohei Kanomata

Researchmap https://researchmap.jp/kyohei_kanomata

Life science

Abstract
We have designed and prepared our own solid catalyst, V-MPS4(Fig. 1), in which oxovanadium is covalently immobilized on the inner surface of pores (inner diameter: 4 nm) of mesoporous silica, aporous inorganic material. Several highly selective catalytic chemical transformations, such as dynamic kinetic resolution, direct coupling of aromatic compounds, and direct nucleophilic substitutionof alcohols, were realized using V-MPS4 (Fig. 2).

synthesis (Fig. 2d).
We speculate that the nanosized pore space of V-MPS4 is thekey to promoting these reactions, and we are currently investigating the mechanism of reaction promotion and further applicationsof our method.

英語版▍ Background & Results
Solid catalysts that are insoluble in organic solvents are often
inferior in terms of catalytic activity and selectivity to homogeneous
catalysts that are soluble in organic solvents. On the other hand,
V-MPS4 catalyzes reactions and exhibits high catalytic activity
and functional group selectivity that surpasses those of the corresponding homogeneous oxovanadium catalysts due to its unique
nano-sized pore environment. In addition, the advantages of thesolid catalyst have enabled its easy recovery and reuse and also
the application to flow synthesis in which catalysts are packed in areaction tube (Fig. 3).
A range of organic compounds, which serve as important synthetic intermediates for pharmaceuticals, agrochemicals, and highly functional chemicals, have been synthesized by using V-MPS4.
This method has several advantages, such as production of littlewastes, high conversion rate, high atom efficiency, and excellent
chemoselectivity and enantioselectivity. In addition, this method issafe, simple to operate, and easy to scale up, and is expected tobe easily applied to industrialization.

▍ Significance of the research and Future perspective
Chemical products are used in every aspect of our lives today,
including clothing and pharmaceuticals. Catalysts are essential forthe efficient production of these products. Catalysts can be classified as either “homogeneous catalysts”, which dissolve in solution,
or “heterogeneous catalysts”, which are solid and do not mix withthe solvent. Homogeneous catalysts are widely used in the production of fine chemicals such as pharmaceuticals and agrochemicals,
which require precise reaction control. On the other hand, homogeneous catalysts require complicated operations to separate theproduct from the catalyst after the reaction, and their reuse is notalways easy. Our own solid catalyst, V-MPS4 has achieved several
highly selective catalytic chemical transformations to solve some ofthese problems.
Some synthetic applications of V-MPS4 include a) the dynamic
kinetic resolution (Fig. 2a), in which racemic alcohols are completely converted into optically pure compounds when used in
combination with immobilized hydrolytic enzymes., viz., lipases; b)
the direct coupling of aromatic compounds (Fig. 2b); c) the direct
nucleophilic substitution of alcohols (Fig. 2c); and continuous flow

Fig. 1 Mesoporous silica-supported vanadium catalyst, V-MPS4.

(a) Dynamic
Fig.Kinetic
1 Resolution

racemates

Optically pure products
100% conversion(b) Direct Coupling ofAromatic Compounds

V-MPS4

Biaryl compounds(c) Direct Nucleophilic
Substitutionof Alcohols
Nucleophilic substitution products(d) Continuous Flow Synthesis

Fig. 2 Examples of chemical transformation using V-MPS4.

P a t e n t Japanese Patent No.5801137, Japanese Patent Application No. 2019-239305
Angew. Chem. Int. Ed. 2013; 52, 3654–3658; Org. Lett. 2019; 21, 2978−2982; Chem. Commun. 2020; 56, 2885–2888; Eur. J. Org. Chem. 2020; 1961–
Tr e a t i s e1967; RSC Adv. 2021; 11, 35342–35350; Eur. J. Org. Chem. 2021; 4417–4422; Synlett 2021; 32, 822–828; Angew. Chem. Int. Ed. 2018; 57, 10278 –10282.
UR
L https://handai-seizo.jp/?lang=en
K e y w o r d solid catalysts, nano-sized porous inorganic materials, optically active compounds, synthetic organic chemistry, low environmental burden