ABOUT
Environmental pollution and global warming cause serious problems. Green chemistry was introduced into the chemical industries to strive for better environmental sustainability. Green chemistry deals with synthesis procedures according to its classic principles, contributing to the sustainability of chemical processes, energy savings, lower toxicity of reagents and final products, reduced damage to the environment and human health, decreasing the risk of global overheating, and more rational use of natural resources and agricultural wastes. Green chemistry research and tools help us to create processes and products that are healthier and more sustainable.
Photochemistry platform
- Photo catalysis is a powerful tool in organic chemical synthesis. The first synthetic application of photo catalysis was in the late 1980s. However, there was a 20-year gap before the advantages were recognized, hampered by the need to use of high-energy light, coupled with the disparate absorption properties of organic molecules. Over the last decade, with the discovery of absorptive organometallic complexes and organic dyes, photoredox catalysis which utilizes visible light to enable single-electron transfer between photo-excitable catalysts and organic molecules, has seen broad adoption for the activation and transformation of organic substrates.
Medicilon Photochemistry Platform
Includes different power UV reactors (254/360nm), 30W-1000W; Covers the wavelength range from 360-520nm;Photocatalyst: Collects common metal catalysts and organic catalysts, and continue to expand according to references; mM fluid reactor is being customizedC(sp3)-C(sp2) coupling reactions
Decarboxylative coupling
Proposed mechanistic pathway of nickel-catalyzed photoredox- decarboxylative arylation[1]C-H cross-coupling
Photoredox, HAT, and nickel-catalyzed cross-coupling: proposed mechanistic pathway and catalyst combination[2]C(sp3)-C(sp3) coupling reactions
Decarboxylative coupling
Carboxylic acid and alkyl halide scope in the dual nickel-catalyzed photoredox sp3-sp3 coupling reaction[3]C-H cross-coupling
The scope of the alkyl bromide coupling partner in the light-enabled selective sp3 C-H alkylation[4]Heteroatom arylations
C-N coupling
Metallaphotoredox-catalyzed amination: amine and arene scope[5]C-O coupling
Alcohol and aryl halide scope in the nickel-catalyzed photoredox C-O coupling reaction[6]Other reactions
Ar-X trifluomethylation
Synthesis of trifluoromethyl(hetero)arenes[7]Decarboxylative fluorination
Decarboxylative Fluorination of Aliphatic Carboxylic Acids via Photoredox Catalysis[8]
Metal catalysts screening platform
- Heteroatom alkylation/arylation and C-C bond formation reactions are among the top 5 most commonly usedmajor organic reactionsMetal catalyzed coupling reactions fail frequently，e.g. the failure rates of C-N couplings are above 50%, due to many pharmaceutically relevant heterocycles are catalyst inhibitorsIn drug discovery, due to the tight project timeline, the availability of intermediates is limited. From the reliable catalyst screening results delivered the decision to continue or stop target synthesis can be made, to avoid wasting time and resource
Catalyst screening flow chart
Selected templates for catalyst screening
Catalyst screening types
Suzuki, Buchwald (C-N/O) screening systems are ready for serviceCatalyst screening equipment
Electrochemical platform
- Electrochemistry acts as a promising green methodology for organic synthesis are described and exemplified. Electrochemical synthesis offers a mild, green and atom efficient route to interesting and useful molecules, thus avoiding harsh chemical oxidising and reducing agents used in traditional synthetic methods.
Custom electrochemical schematic
Basic Components of an Undivided Electrochemical Cell[9]
Synthetic organic electrochemistry applications
Ni-Catalyzed C-N coupling
Nickel-catalyzed amination of aryl halides[10]Ni catalyzed Sp2-Sp3 coupling
Reaction Scope for Electrochemical Cross-Electrophile Couplings[11]C-H Oxidations
Substrate scope of the electrochemical benzylic C–H oxidation reaction[12]Reduction of amide
Plausible reaction mechanism using a Zn anode[13]Heterocycles formation
Formation and cyclization of nitrogen-centered radicals[14]-OCF3, -SCF3, -CF3
Electrochemical Trifluoromethoxylation of (Hetero)aromatics[15]Fluorination
Electrochemical Fluorination of 2,2-Diphenyl-1,3-dithiolane[16]
Summary- Based on green chemical technology, Medicilon's green chemistry platform integrates cutting-edge green technologies such as electrochemistry, photochemistry, metal catalysis and enzyme catalysis into the chemical synthesis routes. Green chemistry remains a high priority in modern organic synthesis and pharmaceutical R&D, with important environmental and economic implications.
Reference:- [1] Zhiwei Zuo,et al. Dual catalysis. Merging photoredox with nickel catalysis: coupling of α-carboxyl sp³-carbons with aryl halides. Science. 2014 Jul 25;345(6195):437-40. doi: 10.1126/science.1255525.[2] Megan H Shaw,et al. Native functionality in triple catalytic cross-coupling: sp³ C-H bonds as latent nucleophiles. Science. 2016 Jun 10;352(6291):1304-8. doi: 10.1126/science.aaf6635.[3] Craig P Johnston, et al. Metallaphotoredox-catalysed sp(3)-sp(3) cross-coupling of carboxylic acids with alkyl halides. Nature. 2016 Aug 18;536(7616):322-5. doi: 10.1038/nature19056.[4] Chip Le,et al. Selective sp³ C-H alkylation via polarity-match-based cross-coupling. Nature. 2017 Jul 6;547(7661):79-83. doi: 10.1038/nature22813.[5] Emily B Corcoran, et al. Aryl amination using ligand-free Ni(II) salts and photoredox catalysis. Science. 2016 Jul 15;353(6296):279-83. doi: 10.1126/science.aag0209.[6] Jack A Terrett, et al. Switching on elusive organometallic mechanisms with photoredox catalysis. Nature. 2015 Aug 20;524(7565):330-4. doi: 10.1038/nature14875.[7] Chip Le, et al. A radical approach to the copper oxidative addition problem: Trifluoromethylation of bromoarenes. Science. 2018 Jun 1;360(6392):1010-1014. doi: 10.1126/science.aat4133.[8] Sandrine Ventre, et al. Decarboxylative Fluorination of Aliphatic Carboxylic Acids via Photoredox Catalysis. J Am Chem Soc. 2015 May 6;137(17):5654-7. doi: 10.1021/jacs.5b02244.[9]Cian Kingston, et al. A Survival Guide for the "Electro-curious". Acc Chem Res. 2020 Jan 21;53(1):72-83. doi: 10.1021/acs.accounts.9b00539.[10] Chao Li, et al. Electrochemically Enabled, Nickel-Catalyzed Amination. Angew Chem Int Ed Engl. 2017 Oct 9;56(42):13088-13093. doi: 10.1002/anie.201707906.[11] Robert J Perkins, et al. Electrochemical Nickel Catalysis for sp2-sp3 Cross-Electrophile Coupling Reactions of Unactivated Alkyl Halides. doi: 10.1021/acs.orglett.7b01598. Org Lett. 2017 Jul 21;19(14):3755-3758.[12]Jason A Marko, et al. Electrochemical benzylic oxidation of C-H bonds. Chem Commun (Camb). 2019 Jan 17;55(7):937-940. doi: 10.1039/c8cc08768g.[13] Kazuhiro Okamoto, et al. Hydrosilane-Mediated Electrochemical Reduction of Amides. J Org Chem. 2021 Nov 19;86(22):15992-16000. doi: 10.1021/acs.joc.1c00931.[14] Huai-Bo Zhao, et al. Amidinyl Radical Formation through Anodic N-H Bond Cleavage and Its Application in Aromatic C-H Bond Functionalization. Angew Chem Int Ed Engl. 2017 Jan 9;56(2):587-590. doi: 10.1002/anie.201610715.[15] Yao Ouyang, et al. Electrochemical Trifluoromethoxylation of (Hetero)aromatics with a Trifluoromethyl Source and Oxygen. Angew Chem Int Ed Engl. 2022 Jan 17;61(3):e202114048. doi: 10.1002/anie.202114048.[16] Naoki Shida, et al. Alkali Metal Fluorides in Fluorinated Alcohols: Fundamental Properties and Applications to Electrochemical Fluorination. J Org Chem. 2021 Nov 19;86(22):16128-16133. doi: 10.1021/acs.joc.1c00692.
