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

The hydroformylation 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 and regioselectivity 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 developing ruthenium-catalyzed hydroformylation, combined with a bulky phosphite ligand, to accomplish selective production of linear aldehydes from 1-alkenes.[1] Moreover, recently we recently reported the branch-selective hydroformylation of 1-alkene using rhodium and tridentate N-Triphos ligand.[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 combining a rhodium-catalyzed hydroformylation and a ruthenium-catalyzed hydrogenation in the same reaction vessel.[3–5]

We also developed retro-hydroformylation reaction, which has rarely been studied before.[6] In the presence of an 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.; Tanaka, Y.; Nozaki, K. Angew. Chem. Int. Ed. 2012, 51, 4283–4387. 10.1002/anie.201108396
[2] Phanopoulos, A.; Nozaki, K. ACS Catal. 2018, 8, 5799–5809. 10.1021/acscatal.8b00566
[3] Takahashi, K.; Yamashita, M.; Ichihara, T.; Nakano, K.; Nozaki, K. Angew. Chem. Int. Ed. 2010, 49, 4488–4490. 10.1002/anie.201001327
[4] Takahashi, K.; Yamashita, M.; Nozaki, K. J. Am. Chem. Soc. 2012, 134, 18746–18757. 10.1021/ja307998h
[5] Yuki, Y.; Takahashi, K.; Tanaka, Y.; Nozaki, K. J. Am. Chem. Soc. 2013, 135, 17393–17400. 10.1021/ja407523j
[6] Kusumoto, S.; Tatsuki, T.; Nozaki, K. Angew. Chem. Int. Ed. 2015, 54, 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]
While the reported syntheses of formic acid from carbon dioxide and water typically employ inorganic bases, our group recently developed the production of formic acid using an organic base with high turnover number.[6,7] Especially, an Ir-PCP chloride complex showed high activity reaching TON of 230,000.[7] Given that formic acid produced with organic bases can be isolated by distillation without neutralization, an industrial application is expected.

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

In addition, we are developing various methods to produce useful chemicals via CO2 reduction. For example, we reported the synthesis of α-hydroxy acids via reductive coupling of an aldehyde and CO2 mediated by a Cu complex.[8]

Recent Publication

[1] Yano, T.; Moroe, Y.; Yamashita, M.; Nozaki, K. Chem. Lett. 2008, 37, 1300–1301. 10.1246/cl.2008.1300
[2] Tanaka, R.; Yamashita, M.; Nozaki, K. J. Am. Chem. Soc. 2009, 131, 14168–14169. 10.1021/ja903574e
[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
[7] Takaoka, S.; Eizawa, A.; Kusumoto, S.; Nakajima, K.; Nishibayashi, Y.; Nozaki, K. Organometallics 2018, 37, 3001–3009. 10.1021/acs.organomet.8b00377
[8] Masada, K.; Kusumoto, S.; Nozaki, K. Org. Lett. in press. 10.1021/acs.orglett.0c00995

1-3. Bond Cleavage/Formation by Metal–Ligand Cooperation

In contrast to classical oxidative addition/reductive elimination directly at a metal center, metal–ligand cooperation, where a metal and a ligand are involved in cleavage/formation of one bond at once, has been attracting attention. The cooperativity has enabled unique reactivity and selectivity which cannot be achieved only by a metal center. Our group has 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 saturated hydrocarbons,[1,2] hydrogenolysis of C–O bonds,[3] and dehydrogenation of amine–borane[4] by employing cyclopentadienyl iridium/rhodium hydride complexes. These transformations can be applied to synthetic organic chemistry, pharmaceutical chemistry and refinery of biomaterials. Indeed, we demonstrated the catalytic cleavage of C–O and C–C bonds in a lignin-model compound by cyclopentadienone metal complexes.[5]

Whereas the reactions above are based on cleavage or formation of H–H bond, recently metal–ligand cooperative cleavage and formation of various chemical bonds have been extensively studied.[6] Our group has reported the first metal–ligand cooperative C–H bond reductive elimination from the hydroxycyclopentadienyl dimethylplatinum(IV) complex.[7] Experimental and theoretical investigations revealed that an outer-sphere involvement of carboxylic acid in the C–H bond formation is critical. Furthermore, the novel cyclopentadienone iridium(I) hydride complex was found to cleave the B–H bond in HBpin into the H+ on the ligand and the B– on the metal, which can be called as umpolung of the B–H bond.[8]

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
[4] Pal, S.; Kusumoto, S.; Nozaki, K. Organometallics 2018, 37, 906–914. 10.1021/acs.organomet.7b00889
[5] Kusumoto, S.; Kishino, M.; Nozaki, K. Chem. Lett. 2020, 49, 477–480. 10.1246/cl.200037
[6] Higashi, T.; Kusumoto, S.; Nozaki, K. Chem. Rev., 2019 119, 10393–10402. 10.1021/acs.chemrev.9b00262
[7] Higashi, T.; Ando, H.; Kusumoto, S.; Nozaki, K. J. Am. Chem. Soc. 2019, 141, 2247–2250. 10.1021/jacs.8b13829
[8] Higashi, T.; Kusumoto, S.; Nozaki, K. Angew. Chem. Int. Ed. in press. 10.1002/anie.202011322

2-1. オレフィンと極性モノマーの配位共重合

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 one of the most effective methods to synthesize functionalized polyolefins. We have thus far achieved the coordination-insertion copolymerization of ethylene and various polar monomers catalyzed by palladium catalysts carrying 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 high 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[3,4] and bidentate ligands containing N-heterocyclic carbene (NHC) such as IzQO ligands[5–8] as novel effective polymerization catalysts.

Using these catalysts, we reported polar monomers such as 1,1-disubstituted ethylene or carbenes.[9–11], that have never been reported previously.

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[12] are effective for the challenging 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] Mitsushige, Y.; Yasuda, H.; Carrow, B.; Ito, S.; Kobayashi, M.; Tayano, T.; Watanabe, Y.; Okuno, Y.; Hayashi, S.; Kuroda, J.; Okumura, Y.; Nozaki, K. ACS Macro Lett. 2018, 7, 305–311. 10.1021/acsmacrolett.8b00034
[5] Nakano, R.; Nozaki, K. J. Am. Chem. Soc. 2015, 137, 10934–10937. 10.1021/jacs.5b06948
[6] Tao, W.; Akita, S.; Nakano, R.; Ito, S.; Hoshimoto, Y.; Ogoshi, S.; Nozaki, K. Chem. Commun. 2017, 53, 2630–2633. 10.1039/C7CC00002B
[7] Akita, S.; Nakano, R.; Ito, S.; Nozaki, K. Organometallics 2018, 37, 2286–2296. 10.1021/acs.organomet.8b00263
[8] Tao, W.; Wang, X.; Ito, S.; Nozaki, K. J. Polym. Sci. Part A: Polym. Chem. 2019, 57, 474–477. 10.1002/pola.29270
[9] Wang, X.; Seidel, F. W.; Nozaki, K. Angew. Chem. Int. Ed. 2019, 58, 12955–12959. 10.1002/anie.201906990
[10] Wang, X.; Nozaki, K. J. Am. Chem. Soc. 2018, 140, 15635–15640. 10.1021/jacs.8b10335
[11] Yasuda, H.; Nakano, R.; Ito, S.; Nozaki, K. J. Am. Chem. Soc. 2018, 140, 1876–1883. 10.1021/jacs.7b12593
[12] 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

2-2. Copolymerization Using Carbon Dioxide

The utilization of carbon dioxide as a C1 resource in synthetic chemistry is highly desirable. Our group reported the productions of polycarbonate and polylactone by copolymerization of carbon dioxide with epoxide and butadiene, respectively.

2-2-1. Alternative Copolymerization of Epoxide with Carbon Dioxide

One of the most promising processes to utilize carbon dioxide is the copolymerization of epoxides with carbon dioxide to produce aliphatic polycarbonates, although low thermophysical properties of aliphatic polycarbonates and contamination of toxic catalyst in the polymer are major challenges to be addressed before successful industrialization. To improve the thermal property of polycarbonates, we have developed regio-regular copolymerization of epoxides and carbon dioxide.[1] An efficient removal of catalysts from polycarbonates by liquid-liquid extraction was developed to realize separation and reuse of catalysts.[3]
In order bypass the use of toxic metals, we developed less toxic and inexpensive iron catalysts for the copolymerization as the first example in the world.[4] We have also developed catalytic systems consisting of various abundant metals such as manganese, titanium, and zirconium.[2,6]

We established a facile method to estimate the catalytic activity of various metal complexes by using DFT calculations.[5] Based on mechanistic studies, we developed multimetallic catalysts for the copolymerization of epoxides with carbon dioxide, where the multimetallic catalysts cooperatively activate carbon dioxide and epoxides on adjacent metal centers.[7,8]

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
[6] Robert, C.; Ohkawara, T.; Nozaki, K. Chem. Eur. J. 2014, 20, 4789–4795. 10.1002/chem.201303703
[7] Hatazawa, M.; Takahashi, R.; Deng, J.; Houjou, H.; Nozaki, K. Macromolecules 2017, 50, 7895–7900. 10.1021/acs.macromol.7b01130
[8] Asaba, H.; Iwasaki, T.; Hatazawa, M.; Deng, J.; Nagae, H.; Mashima, K.; Nozaki, K. in press. 10.1021/acs.inorgchem.0c01156

2-2-2. Copolymerization of Carbon Dioxide with Dienes

As carbon dioxide is in the most stable form of carbon, its transformation requires additional physical or chemical energy source. Therefore, transformations employing cheap and abundant chemical resources such as alkenes and dienes have been desired for mass-utilization of carbon dioxide. In this context, the polymer synthesis from carbon dioxide and alkenes has long been pursued but have remained elusive. 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.[1] Subsequent free-radical polymerization of the lactone intermediate afforded polymers of high molecular weight with a carbon dioxide content of 33 mol% (29 wt%).

We revealed the structure of the polymer changes reversibly in the presence of water or amine.[2] The ring-opened polymer by water was found to undergo the ring-closing reaction by simply heating to give the original polylactone structure. The unique reversible reaction would originate from the fixed geometry of the carboxylic and hydroxy groups in the rigid polymer chain.

Recent Publication

[1] Nakano, R.; Ito, S.; Nozaki, K. Nature Chem. 2014, 6, 325–331. 10.1038/nchem.1882
[2] Moon, S.; Masada, K.; Nozaki, K. J. Am. Chem. Soc. 2019, 141, 10938–10942. 10.1021/jacs.9b03205

3-1. Synthesis of Helicene Analogs

Helicenes, ortho-fused aromatic rings in a helical fashion, 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.[1–4] With regard to phosphorahelicene, possessing a phosphorus atom, each enantiomers stack into columnar structures in a crystal state and afford an anisotropic crystal.[2]

Helicene-like compounds, featuring 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.[5,6] 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
[4] Oyama, H.; Akiyama, M.; Nakano, K.; Naito, M.; Nobusawa, K.; Nozaki, K. Org. Lett. 2016, 18, 3654–3657. 10.1021/acs.orglett.6b01708
[5] Akiyama, M.; Nozaki, K. Angew. Chem. Int. Ed. 2017, 56, 2040–2044. 10.1002/anie.201611488
[6] Akiyama, M.; Tsuchiya, Y.; Ishii, A.; Hasegawa, M.; Kurashige, Y.; Nozaki, K. Chem. Asian. J. 2018, 13, 1902–1905. 10.1002/asia.201800780

3-2.Synthesis of Polycyclic Aromatic Hydrocarbons Including Heteroatom

Polycyclic aromatic hydrocarbons (PAHs), which are composed of multiple benzene rings, are expected to show attractive physical properties, such as conductivity/semi-conductivity and photophysical properties arising from their expanded π-systems. PAHs including hetero-atoms are attracting much interests because the introduction of heteroatom into PAHs structure enables modifications of the physical properties. We recently developed 9a-azaphenalenyl-fused azomethine ylides and successfully applied them to the 1,3-dipolar cycloaddition with various alkynes and alkenes.[1] Subsequent oxidative dehydrogenation of the cycloadducts gave PHAs containing a highly-fused pyrrole motif.

We further succeeded in the production of azapentabenzocorannulene which had a bowl shaped structure.[2] The 1,3-dipolar cycloaddition to corannulene[3] allowed us to synthesize highly curved nitrogen-containing PAHs as a partial C80-xNx structure.[4]

We also developed fivefold borylation/arylation sequence, which was employed in the synthesis of liquid-crystalline azapentabenzocorannulenes with five 3,4,5-trialkoxyphenyl groups. The multi-functionalized azapentabenzocorannulenes assembled into 1D hexagonal columnar structures.[5]

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] Tokimaru, Y.; Ito, S.; Nozaki, K. Angew. Chem. Int. Ed. 2017, 56, 15560–15564. 10.1002/anie.201707087
[4] Tokimaru, Y.; Ito, S.; Nozaki, K. Angew. Chem. Int. Ed. 2018, 57, 9818–9822. 10.1002/anie.201707087
[5] Nagano, T.; Nakamura, K.; Tokimaru, Y.; Ito, S.; Miyajima, D.; Aida, T. Nozaki, K. Chem. Eur. J. 2018, 24, 14075–14078. 10.1002/chem.201803676

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.