Reseach in the Nozaki Group

Our research focuses on organic chemistry. The goal of our research is to discover, develop, and understand new reactions mediated by homogeneous catalysis for organic and polymer synthesis. Our interests further extend to the functions of new materials created by our original methods. We pursue our interests for both the beauty of science and to positively impact society.

Catalyst CatalyticTransformations Functional PolymerSynthesis Synthesis ofAromatic Compounds HeterogeneousCatalysis

The followings are our research topics in recent five years:

1-1.Hydroformylation

Hydroformylation, a transition-metal catalyzed reaction producing aldehydes from alkenes, carbon monoxide and hydrogen, is one of the most important reactions in industry. We have been engaged in developing new transition metal catalysts to improve the catalytic activity, regioselectivity, and cost-effectiveness of the hydroformylation reaction.
In general, group 9 metals such as rhodium or cobalt are used as catalysts for hydroformylation reactions. In our research, we succeeded in ruthenium-catalyzed hydroformylation, combined with a bulky phosphate ligand, to accomplish selective production of linear aldehydes from 1-alkenes.[2]

In industry, aliphatic alcohols are generally produced by two step procedures of olefin hydroformylation and subsequent hydrogenation. In this context, we developed an effective one-pot process to produce linear alcohols from 1-alkenes by combination of a rhodium catalyst for hydroformylation and a ruthenium catalyst for hydrogenation.[1,3]

We also developed retro-hydroformylation reaction, which has rarely been studied before.[5] In the presence of iridium catalyst, long-chain aliphatic aldehydes were converted into the corresponding alkenes, carbon monoxide, and dihydrogen in high yield. This reaction might open the door for the utilization of renewable resources as feedstocks.

Recent Publication

[1] Takahashi, K.; Yamashita, M.; Ichihara, T.; Nakano, K.; Nozaki, K. Angew. Chem. Int. Ed. 2010, 49, 4488-4490. 10.1002/anie.201001327
[2] Takahashi, K.; Yamashita, M.; Tanaka, Y.; Nozaki, K. Angew. Chem. Int. Ed. 2012, 51, 4283-4387. 10.1002/anie.201108396
[3] Takahashi, K.; Yamashita, M.; Nozaki, K. J. Am. Chem. Soc. 2102, 134, 18746-18757. 10.1021/ja307998h
[4] Yuki, Y.; Takahashi, K.; Tanaka, Y.; Nozaki, K. J. Am. Chem. Soc. 2013, 135, 17393-17400. 10.1021/ja407523j
[5] Kusumoto, S.; Tatsuki, T.; Nozaki, K. Angew. Chem. Int. Ed. 201554, 8458-8461. 10.1002/anie.201503620

1-2. Formic Acid Production by Hydrogenation of Carbon Dioxide

Formic acid is an important chemical used as preservatives and insecticides. Current industrial production of formic acid generally employ carbon monoxide and water, but an ideal production process would be hydrogenation of carbon dioxide, which is a cheap, more abundant and less toxic carbon resource than carbon monoxide.[3-5]

Based on our background about iridium complexes bearing a PNP-pincer type tridentate ligand,1,2 we found that an Ir-PNP trihydride complex promotes hydrogenation of carbon dioxide.3,4 This catalyst is one of the most active catalyst for hydrogenation of CO2, reaching TOF (turnover frequency) of 150,000 h-1 (highest TOF at that time) and TON (turnover number) of 3,500,000 (highest ever).

Recent Publication

[1] Yano, T.; Moroe, Y.; Yamashita, M.; Nozaki, K. Chem. Lett. 2008, 37, 1300-1301. doi
[2] Tanaka, R.; Yamashita, M.; Nozaki, K. J. Am. Chem. Soc. 2009, 131, 14168-14169. 10.1021/ja905950g
[3] Tanaka, R.; Yamashita, M.; Chung, L. W.; Morokuma, K.; Nozaki, K. Organometallics 2011, 30, 6742-6750. 10.1021/om2010172
[4] Yamashita, M.; Moroe, Y.; Yano, T.; Nozaki, K. Inorg. Chim. Acta 2011, 369, 15-18. 10.1016/j.ica.2010.08.034
[5] Shintani, R.; Nozaki, K. Organometallics 2013, 32, 2459-2462. 10.1021/om400175h
[6] Aoki, W.; Wattanabinin, N.; Kusumoto, S.; Nozaki K. Bull. Chem. Soc. Jpn. 2016, 89, 113-124. 10.1246/bcsj.20150311

1-3. Catalytic Reactions by Metal-Ligand Cooperation

Metal-ligand cooperation can enable unique reactivity and selectivity which are not possible only by a metal center. Nozaki group have investigated the catalytic activity of transition-metal complexes bearing redox active ligands for various bond-cleavage and bond-forming reactions. Recently, we developed the first direct and acceptorless dehydrogenation of carbon—carbon single bonds adjacent to various polar functional groups[1,2] and hydrogenolysis of C—O bonds.[3] These transformation can be applied to synthetic organic chemistry, pharmaceutical chemistry and refinery of biomaterials.

Recent Publication

[1] Kusumoto, S.; Akiyama, M.; Nozaki, K. J. Am. Chem. Soc. 2013, 135, 18726–18729. 10.1021/ja409672w
[2] Ando, H.; Kusumoto, S.; Wu, W.; Nozaki, K. Organometallics 2017, 36, 2317–2322. 10.1021/acs.organomet.7b00245
[3] Kusumoto, S; Nozaki, K. Nat. Commun. 2015, 6, 6296. 10.1038/ncomms7296

1-4. Alternative Copolymerization of Epoxide with Carbon Dioxide

See 2-1

2-1. Alternative Copolymerization of Epoxide with Carbon Dioxide

Utilization of carbon dioxide as a C1 resource of synthetic chemistry has been highly desired. One of the most efficient ways to utilize carbon dioxide would the copolymerization of epoxide with carbon dioxide to produce aliphatic polycarbonate. Fragility of aliphatic polycarbonate and toxicity of the remaining catalyst in the polymer, however, are the major shortcomings for industrialization. With the aim of improving the thermal property of polycarbonate, we developed regio-regular copolymerization of epoxide and carbon dioxide .[1]
In recent research, we have investigated two different approaches to reduce toxicity of redundant catalysts: (1) use of cheap and low-toxic metal as a catalyst and (2) efficient removal of the remaining catalyst after polymerization. In the first approach, we developed the first iron, titanium and zirconium catalysts for the polymerization of epoxides with carbon dioxide.[3,4] On the course of this study, we established a facile method to estimate the catalytic activity of various metal complexes by using DFT calculation.[5]

In the second approach to achieve efficient catalyst removal, we developed an easy and efficient protocol to separate and recycle catalysts by phase separation extraction using long-chain fatty acids.

Recent Publication

[1] Nakano, K.; Hashimoto, S.; Nakamura, M.; Kamada, T.; Nozaki, K. Angew. Chem. Int. Ed. 2011, 50, 4868-4871. 10.1002/anie.201007958
[2] Nakano, K.;Kobayashi. K.; Nozaki, K. J. Am. Chem. Soc. 2011, 133, 10720-10723. 10.1021/ja203382q
[3] Nakano, K.; Fujie, R.; Shintani, R.; Nozaki, K. Chem. Commun. 2013, 49, 9332-9334. 10.1039/C3CC45622F
[4] Nakano, K.; Kobayashi, K.; Ohkawara, T.; Imoto, H.; Nozaki, K. J. Am. Chem. Soc. 2013, 135, 8456-8459. 10.1021/ja4028633
[5] Ohkawara, T.; Suzuki, K.; Nakano, K.; Mori, S.; Nozaki, K. J. Am. Chem. Soc. 2014, 136, 10728-10735. 10.1021/ja5046814

2-2. Coordination-Insertion Copolymerization of Olefins with Polar Monomers

Incorporation of polar functional groups into the main chain of polyolefins can improve their hydrophilic properties such as adhesion, dyeability, and colorability, which drastically expand the range of applications. To this end, we focus on the copolymerization of olefins with polar monomers as the most effective method to synthesize functionalized polyolefins. We have thus far achieved the coordination-insertion copolymerization of ethylene and various polar monomers catalyzed by palladium catalysts ligated by a phosphine-sulfonate ligand,[1] but for industrial applications, further improvement of activity and molecular weight of polymer is desired. Recently, we investigated the steric effect of substituents on phosphine-sulfonate ligands systematically to find catalysts affording copolymers with exceptionally higher molecular weights than previous catalyst systems.[2]

Based on a hypothesis that the use of unsymmetric bidentate ligands is the key to the successful coordination-insertion copolymerization of ethylene with polar monomers, we have developed palladium catalysts bearing bisphosphine monoxide ligands[3] and IzQO ligands[4] as novel effective polymerization catalysts.

We have focused on the coordination-insertion copolymerization of propylene and polar monomers, which is much more difficult than ethylene/polar monomer copolymerization. We have found that Pd/IzQO catalysts[4] and phosphine-sulfonate catalysts[5] are effective for this copolymerization.

Recent Publication

[1] Ito, S.; Kanazawa, M.; Munakata, K.; Kuroda, J.; Okumura, Y.; Nozaki, K. J. Am. Chem. Soc. 2011, 133, 1232–1235. 10.1021/ja1092216
[2] Ota, Y.; Ito, S.; Kuroda, J.; Okumura, Y.; Nozaki, K. J. Am. Chem. Soc. 2014, 136, 11898–11901. 10.1021/ja505558e
[3] Mitsushige, Y.; Carrow, B. P.; Ito, S.; Nozaki, K. Chem. Sci. 2016, 7, 737–744. 10.1039/C5SC03361F
[4] Nakano, R.; Nozaki, K. J. Am. Chem. Soc. 2015, 137, 10934-10937. 10.1021/jacs.5b06948
[5] Ota, Y.; Ito, S.; Kobayashi, M.; Kitade, S.; Sakata, K.; Tayano, T.; Nozaki, K. Angew. Chem. Int. Ed. 2016, 55, 7505-7509. 10.1002/anie.201600819

2-3. Copolymerization of Carbon Dioxide with Dienes

Although carbon dioxide has attracted broad interest as a renewable carbon feedstock, the final product of combustion is in the most stable form of carbon atom. Therefore its transformation requires additional physical or chemical energy source, and then transformation employing cheap and abundant chemical resources such as alkenes and dienes has been desired as ideal method to mass-utilization of carbon dioxide. In this context, the polymer synthesis from carbon dioxide and alkenes has long been pursued but remained an elusive endeavor. A major obstacle for this process is that the propagation step involving carbon dioxide is endothermic; typically, attempted reactions between carbon dioxide and an olefin preferentially yield olefin homopolymerization.
We reported a strategy to circumvent the thermodynamic and kinetic barriers for copolymerizations of carbon dioxide and olefins by using a metastable lactone intermediate, 3-ethylidene-6-vinyltetrahydro-2H-pyran-2-one, which is formed by the palladium-catalyzed condensation of carbon dioxide and 1,3-butadiene. Subsequent free-radical polymerization of the lactone intermediate afforded polymers of high molecular weight with a carbon dioxide content of 33 mol% (29 wt%).

Recent Publication

[1] Nakano, R.; Ito, S.; Nozaki, K.Nature Chem. 2014, 6, 325-331. 10.1038/nchem.1882

3-1. Synthesis of Polycyclic Aromatic Hydrocarbons

3-1-1. Synthesis of Helicene Analogs

Helicenes, ortho-fused aromatic rings with helical chirality, show characteristic properties derived from their quasi-planarity and helical chirality. We synthesized helicene analogues possessing a five-membered ring containing a heteroatom, such as nitrogen (N), oxygen (O), phosphorus (P), and silicon (Si), and found that they showed various properties depending on the induced heteroatom. With regard to phospholahelicene, possessing a phosphorus atom, each enantiomers stack into columnar structures in a crystal state and afford an anisotropic crystal.

Helicene-like compounds, which are introduced either silicon or sp3-carbon, exhibited the highest value of circularly-polarized luminescence and fluorescence quantum yield among the small molecules ever reported.[3][4]

With deprotonated helicene-like hydrocarbon as a cyclopentadienyl ligand, helicene-metal complexes are synthesized.[5] They could be isolated in their enantiopure form, which enabled investigation of inversion behavior of the helical structure and chiroptical properties. It was found that the bis-ruthenium complex exhibited phosphorescence in both a solution and a solid state, in sharp contrast to the non-emissive nature of monometallic complexes.

Recent Publication

[1] Nakano, K.; Hidehira, Y.; Takahashi, K.; Hiyama, T.; Nozaki, K. Angew. Chem. Int. Ed. 2005, 44, 7136-7138. 10.1002/anie.200502855
[2] Nakano, K.; Oyama, H.; Nishimura, Y.; Nakasako, S.; Nozaki, K. Angew. Chem. Int. Ed. 2012, 51, 695-699. 10.1002/anie.201106157
[3] Oyama, H.; Nakano, K.; Harada, R.; Kuroda, R; Naito, M.; Nobusawa, K.; Nozaki, K.Org. Lett. 2013, 15, 2104-2107. 10.1021/ol4005036

3-1-2.Synthesis of Polycyclic Aromatic Hydrocarbons Including Heteroatom

Polycyclic aromatic hydrocarbons (PAHs), which are composed of multiple organic rings, are expected to show attractive physical properties, such as conductivity/semi-conductivity and luminescence properties, Especially, PAHs including hetero-atoms are attracting much interests because the introduction of heteroatom into PAHs structure effects the physical properties. We are now trying to develop a new reaction which constructs PAHs including hetero-atom structure. Until now, we developed a novel fused azomethine ylides which have 9a-azaphenalenyl structure and found that the azomethineylides undergo 1,3-dipolar cycloaddition with various alkynes and alkenes in moderate yield.[1] The obtained cycloadducts were found to be converted to PAHs containing a highly-fused pyrrole structure by oxidative dehydrogenation, including benzene-fused azacorannulene.[2]

Recent Publication

[1] Ito,S.; Tokimaru, Y.; Nozaki, K. Chem. Commun. 2015, 51, 221-224. 10.1039/C4CC06643J
[2] Ito,S.; Tokimaru, Y.; Nozaki, K. Angew. Chem. Int. Ed. 2015, 54, 7256-7260. 10.1002/anie.201502599

3-2.Synthesis of Polymers with Aromatic Rings

3-2-1. Formal Aryne Polymerization

Aryne, a hydrocarbon molecule derived from an arene by abstraction of two hydrogen atoms from adjacent carbon atoms, is one of the most useful intermediates to introduce ortho-arylene group in organic compounds. However, there are few examples of polymerization of aryne because of the difficulty to control its high reactivity attributed to low LUMO level. Instead of aryne itself, we focused on a synthetic equivalent of aryne, [2.2.1]oxabicyclic alkenes, which are stable and easily available as aryne equivalents, and can be transformed into ortho-arylene group by coordination-insertion and following dehydration. Until now, we developed the homopolymerization of aryne equivalents to give poly(o-arylene)s with naphthalene rings, anthracene rings, and triphenylene rings.[1] Copolymerization of aryne equivalents with carbon monoxide[2] or ethylene[3] was also accomplished.

Recent Publication

[1] Ito, S.; Takahashi, K.; Nozaki, K. J. Am. Chem. Soc. 2014, 136, 7547-7550. 10.1021/ja502073k
[2] Ito, S.; Wang, W.; Nishimura, K.; Nozaki, K. Macromolecules 2015, 48, 1959–1962. 10.1021/acs.macromol.5b00315
[3] Ito, S.; Wang, W.; Nozaki, K. Polym. J. 2015, 47, 474–480. 10.1038/pj.2015.27

3-2-2. The polymerization involving 1,4-rhodium migration

Rhodium(I) complexes are known to undergo intramolecular 1,4-rhodium migration from an alkyl- or alkenylrhodium species to an arylrhodium species. However, this attractive feature of rhodium(I) complexes has never been exploited in the polymerization chemistry despite its potential utility for synthesizing a variety of new types of polymers that are currently inaccessible. So, we are developing the polymerization reaction through an insertion/1,4-rhodium migration sequence. The polymers could be also expected to have new properties. We have reported a rhodium-catalyzed polymerization of 3,3-diarylcyclopropenes involving a 1,4-rhodium migration to give a new class of polymers, poly(cyclopropyleneo-phenylene)s, with high efficiency.

Recent Publication

[1] Shintani, R.; Iino, R.; Nozaki, K. J. Am. Chem. Soc. 2014, 136, 7849-7852. 10.1021/ja5032002

4. Development of novel organic reactions using structurally and mechanistically well-defined heterogeneous catalysts

Heterogeneous catalysts have widely been utilized in the petrochemical industry, and about 80% of basic chemical products have been synthesized using heterogeneous catalysts. However, because of the difficulties in the fine-control of catalytically active sites in heterogeneous catalysts, homogeneous catalysts, which are much easier to fine-tune the steric and electronic properties of active metal centers, have played an irreplaceable role for the highly regio-, stereo-, and enantioselective synthesis of fine chemicals. We are aiming at the creation of structurally and mechanistically well-defined heterogeneous catalysts, which possess advantages of both heterogeneous and homogeneous catalysts, to develop highly challenging organic reactions.