About the Research
Synthetic organic chemistry (development of new chemical reactions, catalyst design)
See my CV & Publication List.
In our research group, we mainly focus on developing new chemical transformations to synthesize high-value-added molecules (e.g., amino acids) guided by quantum chemical calculations (Gaussian and the AFIR method implemented in the GRRM program). We intensively investigate various kinds thermal/light/electrochemical-promoted reactions and catalytic transformations, such as:
Ionic transformations: Controlling highly reactive species such as singlet carbenes, nitrenes, benzynes, and carbocations can lead to the development of new ionic transformations. Using these transient intermediates allows efficiently incorporating carbon dioxide (CO2), an abundant, inexpensive, nontoxic, and renewable C1 source, into more complex molecules.
- Nat. Synth. 2022, 1 (10), 804-814. DOI: 10.1038/s44160-022-00128-y
- Chem. Eur. J. 2021, 27 (39), 10040-10047. DOI: 10.1002/chem.202100812
- Chem. Sci. 2020, 11 (29), 7569-7577. DOI: 10.1039/D0SC02089C
- Angew. Chem., Int. Ed. 2011, 50 (6), 1393-1396. DOI: 10.1002/anie.201006422
Radical transformations: The behavior of radical species can be estimated by quantum chemical calculations, which may lead to the development of novel free-radical-mediated transformations. To generate proposed radicals from neutral molecules, we have already used LEDs that emit light of varying wave length (from UV to red light), various kinds of photocatalysts, electrochemical devices, and a flow system that can control the reactivity of the generated radicals. Specifically, we are now focusing on ethylene difunctionalization via a radical intermediate under irradiation with visible light.
- Nat. Commun. 2022, 13, 7034. DOI: 10.1038/s41467-022-34546-5
- J. Am. Chem. Soc. 2022, 144 (8), 3685-3695. DOI: 10.1021/jacs.1c13032
- Angew. Chem., Int. Ed. 2022, 61, e202211936. DOI: 10.1002/anie.202211936
- ACS Omega 2021, 6 (49), 33846-33854. DOI: 10.1021/acsomega.1c05102
Pericyclic reactions: Pericyclic reactions are perfectly atom-economical transformations, in which the reaction modes can be precisely predicted by quantum chemical calculations using the AFIR method. The AFIR method can successfully predict products or reactants whose stereochemistry is governed by the Woodward-Hoffmann rules. Taking advantage of this excellent calculation platform, we are currently developing new pericyclic reactions.
- J. Am. Chem. Soc. 2022, in press. DOI: 10.1021/jacs.2c09830
Transition-metal-catalyzed transformations: We are currently also focusing on the development of new functionalization methods for C-H and C-C bonds that are difficult to cleave without transition-metal catalysts. To realize these transformations, effective catalyst structures can be designed based on quantum chemical calculations. In this respect, transition-metal-catalyzed CO2 incorporation triggered by the catalytic cleavage of C-H bonds is studied to synthesize high-value-added carboxylic acids from simple starting materials. Furthermore, we have started a new project for the development of new chemical transformations promoted by artificial metalloenzymes including Fe, Ir, etc.
- Chem. Asian J. 2021, 16 (24), 4072-4080. DOI: 10.1002/asia.202100989
- Adv. Synth. Catal. 2020, 362 (6), 1275-1280. DOI: 10.1002/adsc.201901533
- J. Am. Chem. Soc. 2017, 139 (17), 6094-6097. DOI: 10.1021/jacs.7b02775
- Chem. Eur. J. 2015, 21 (46), 16391-16394. DOI: 10.1002/chem.201503359
- Asian J. Org. Chem. 2022, 11 (5), e202200082. DOI: 10.1002/ajoc.202200082
- Chem. Asian J. 2019, 14 (12), 2038-2047. DOI: 10.1002/asia.201900379
Representative Research Achievements
- Mita, T.*; Takano, H.; Hayashi, H.; Kanna, W.; Harabuchi, Y.; Houk, K. N.; Maeda, S.* “Prediction of High-Yielding Single-Step or Cascade Pericyclic Reactions for the Synthesis of Complex Synthetic Targets” J. Am. Chem. Soc. 2022, in press.
- Takano, H.; Katsuyama, H.; Hayashi, H.; Kanna, W.; Harabuchi, Y.; Maeda, S.*; Mita, T.* “A Theory-driven Synthesis of Symmetric and Unsymmetric 1,2-Bis(diphenylphosphino)ethane Analogues via Radical Difunctionalization of Ethylene” Nat. Commun. 2022, 13, 7034.
- Hayashi, H.; Katsuyama, H.; Takano, H.; Harabuchi, Y.; Maeda, S.*; Mita, T.* “In Silico Reaction Screening with Difluorocarbene for N-Difluoroalkylative Dearomatization of Pyridines” Nat. Synth. 2022, 1 (10), 804-814.
- You, Y.; Kanna, W.; Takano, H.; Hayashi, H.; Maeda, S.*; Mita, T.* “Electrochemical Dearomative Dicarboxylation of Heterocycles with Highly Negative Reduction Potentials” J. Am. Chem. Soc. 2022, 144 (8), 3685-3695.
- Harabuchi, Y.*; Hayashi, H.; Takano, H.; Mita, T.; Maeda, S.* “Oxidation and Reduction Pathways in the Knowles Hydroamination via a Photoredox-Catalyzed Radical Reaction” Angew. Chem., Int. Ed. 2022, 61, e202211936.
- Takano, H.; You, Y.; Hayashi, H.; Harabuchi, Y.; Maeda, S.*; Mita, T.* “Radical Difunctionalization of Gaseous Ethylene Guided by Quantum Chemical Calculations: Selective Incorporation of Two Molecules of Ethylene” ACS Omega 2021, 6 (49), 33846-33854.
- Kanna, W.; Harabuchi, Y.; Takano, H.; Hayashi, H.; Maeda, S.*; Mita, T.* “Carboxylation of a Palladacycle Formed via C(sp3)-H Activation: Theory-Driven Reaction Design” Chem. Asian J. 2021, 16 (24), 4072-4080.
- Hayashi, H.; Takano, H.; Katsuyama, H.; Harabuchi, Y.; Maeda, S.*; Mita, T.* “Synthesis of Difluoroglycine Derivatives from Amines, Difluorocarbene, and CO2: Computational Design, Scope, and Application” Chem. Eur. J. 2021, 27 (39), 10040-10047.
- Mita, T.*; Harabuchi, Y.; Maeda, S.* “Discovery of a Synthesis Method for a Difluoroglycine Derivative Based on a Path Generated by Quantum Chemical Calculations” Chem. Sci. 2020, 11 (29), 7569-7577.
- Mita, T.*; Uchiyama, M.; Sato, Y.* “Catalytic Intramolecular Coupling of Ketoalkenes by Allylic C(sp3)-H Bond Cleavage: Synthesis of Five- and Six-Membered Carbocyclic Compounds” Adv. Synth. Catal. 2020, 362 (6), 1275-1280.
- Mita, T.*; Ishii, S.; Higuchi, Y.; Sato, Y.* “Pd-Catalyzed Dearomative Carboxylation of Indolylmethanol Derivatives” Org. Lett. 2018, 20 (23), 7603-7606.
- Michigami, K.; Mita, T.*; Sato, Y.* “Cobalt-Catalyzed Allylic C(sp3)-H Carboxylation with CO2” J. Am. Chem. Soc. 2017, 139 (17), 6094-6097.
- Mita, T.*; Sugawara, M.; Sato, Y.* “One-Pot Synthesis of α-Amino Acids through Carboxylation of Ammonium Ylides with CO2 Followed by Alkyl Migration” J. Org. Chem. 2016, 81 (12), 5236-5243.
- Mita, T.*; Higuchi, Y.; Sato, Y.* “Highly Regioselective Palladium-Catalyzed Carboxylation of Allylic Alcohols with CO2” Chem. Eur. J. 2015, 21 (46), 16391-16394.
- Mita, T.*; Sugawara, M.; Saito, K.; Sato, Y.* “Catalytic Enantioselective Silylation of N-Sulfonylimines: Asymmetric Synthesis of α-Amino Acids from CO2 via Stereospecific Carboxylation of α-Amino Silanes” Org. Lett. 2014, 16 (11), 3028-3031.
- Mita, T.*; Ikeda, Y.; Michigami, K.; Sato, Y.* “Iridium-Catalyzed Triple C(sp3)-H Borylations: Construction of Triborylated Sp3-Carbon Centers” Chem. Commun. 2013, 49 (49), 5601-5603.
- Mita, T.*; Chen, J.; Sugawara, M.; Sato, Y.* “One-Pot Synthesis of α-Amino Acids from Imines through CO2Incorporation: An Alternative Method for Strecker Synthesis” Angew. Chem. Int. Ed. 2011, 50 (6), 1393-1396.
- Press Release Automated chemical reaction prediction: now in stereo
- Method for automated reaction path search of photoredox reactions enables determination of the Knowles hydroamination mechanism
- Press Release Simplified process shines light on new catalyst opportunities
- Press Release Simulations provide map to treasure trove of fluorinated compounds
- Press Release CO2 recycling and efficient drug development—tackling two problems with one reaction
- Computational-chemistry-guided development of the difunctionalization of ethylene gas: selective incorporation of two ethylene molecules
- Carboxylation of a Palladacycle Formed via C(sp3)–H Activation: AFIR Theory‐Driven Reaction Design
- Computationally Designed Synthesis of Difluoroglycine Derivatives from Amines, Difluorocarbene, and Carbon Dioxide
- Novel computer-assisted chemical synthesis method cuts research time and cost