Deuterium labelling by electrochemical splitting of heavy water

Jia Liu , Zhongxin Chen , Ming Joo Koh , Kian Ping Loh

Energy Materials ›› 2021, Vol. 1 ›› Issue (2) : 100016

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Energy Materials ›› 2021, Vol. 1 ›› Issue (2) :100016 DOI: 10.20517/energymater.2021.19
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Deuterium labelling by electrochemical splitting of heavy water

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Abstract

Deuterium incorporation is crucial in organic synthesis and has wide applications in the pharmaceutical industry. State-of-the-art H/D isotope exchange and chemical defunctionalization for deuterium incorporation suffer from significant drawbacks, including expensive deuterium sources, low deuteration efficiency and poor selectivity. In this perspective, we highlight an alternative pathway for forming C-D bonds by electrocatalytic heavy water splitting (D2O) under mild conditions. In addition, the intrinsic mechanism and examples of the synthesis of deuterated pharmaceuticals are discussed in detail. Finally, we present the challenges facing this field and provide an overall perspective on future research directions.

Keywords

Deuteration / water splitting / electrocatalysis / pharmaceuticals / H/D exchange

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Jia Liu, Zhongxin Chen, Ming Joo Koh, Kian Ping Loh. Deuterium labelling by electrochemical splitting of heavy water. Energy Materials, 2021, 1(2): 100016 DOI:10.20517/energymater.2021.19

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References

[1]

Urey HC,Murphy GM.A hydrogen isotope of mass 2.Phys Rev1932;39:164-5

[2]

Atzrodt J,Fey T.The renaissance of H/D exchange.Angew Chem Int Ed Engl2007;46:7744-65

[3]

Crabtree RH.Organometallic alkane CH activation.J Organomet Chem2004;689:4083-91

[4]

Ribas X,Parella T,Solà M.Regiospecific C-H bond activation: reversible H/D exchange promoted by CuI complexes with triazamacrocyclic ligands.Angew Chem2006;118:3007-10

[5]

Wiberg KB.The deuterium isotope effect.Chem Rev1955;55:713-43

[6]

Michelotti A.40 years of hydrogen-deuterium exchange adjacent to heteroatoms: a survey.Synthesis2019;51:1319-28

[7]

Mullard A.FDA approves first deuterated drug.Nat Rev Drug Discov2017;16:305

[8]

Schmidt C.First deuterated drug approved.Nat Biotechnol2017;35:493-4

[9]

Atzrodt J,Kerr WJ.C-H functionalisation for hydrogen isotope exchange.Angew Chem Int Ed Engl2018;57:3022-47

[10]

Junk T.Hydrogen isotope exchange reactions involving C-H (D, T) bonds.Chem Soc Rev1997;26:401-6

[11]

Rettner CT.Quantum-state distributions for the HD product of the direct reaction of H(D)/Cu(111) with D(H) incident from the gas phase.J Chem Phys1996;104:2732-9

[12]

Alonso F,Yus M.Metal-mediated reductive hydrodehalogenation of organic halides.Chem Rev2002;102:4009-91

[13]

Hatano N,Takekiyo T,Yoshimura Y.Anomalous conformational change in 1-butyl-3-methylimidazolium tetrafluoroborate-D2O mixtures.J Phys Chem A2012;116:1208-12

[14]

Li H,Dong Y.A selective and cost-effective method for the reductive deuteration of activated alkenes.Tetrahedron Letters2017;58:2757-60

[15]

Than C,Andres H.Tritium and deuterium labelling studies of alkali metal borohydrides and their application to simple reductions.J Label Compd Radiopharm1996;38:693-711

[16]

Puleo TR,Bandar JS.Catalytic α-selective deuteration of styrene derivatives.J Am Chem Soc2019;141:1467-72

[17]

Zarate C,Bezdek MJ,Chirik PJ.Ni(I)-X complexes bearing a bulky α-diimine ligand: synthesis, structure, and superior catalytic performance in the hydrogen isotope exchange in pharmaceuticals.J Am Chem Soc2019;141:5034-44

[18]

Yu RP,Rivera N,Chirik PJ.Iron-catalysed tritiation of pharmaceuticals.Nature2016;529:195-9

[19]

Koniarczyk JL,Overgard A,McNally A.A general strategy for site-selective incorporation of deuterium and tritium into pyridines, diazines, and pharmaceuticals.J Am Chem Soc2018;140:1990-3

[20]

Mo X,Dansereau J,Hall DG.Unsymmetrical diarylmethanes by ferroceniumboronic acid catalyzed direct friedel-crafts reactions with deactivated benzylic alcohols: enhanced reactivity due to ion-pairing effects.J Am Chem Soc2015;137:9694-703

[21]

Harbeson SL.Deuterium medicinal chemistry: a new approach to drug discovery and development.Med Chem News2014;24:8-22

[22]

Wang D,Wang J,Chen B.Base-catalyzed hydrogen-deuterium exchange and dehalogenation reactions of 1,2,3-triazole derivatives.Tetrahedron2016;72:6375-9

[23]

Zhu N,Wan WM,Bao H.Practical method for reductive deuteration of ketones with magnesium and D2O.Org Lett2020;22:991-6

[24]

Rowbotham JS,Lenz O,Vincent KA.Bringing biocatalytic deuteration into the toolbox of asymmetric isotopic labelling techniques.Nat Commun2020;11:1454 PMCID:PMC7081218

[25]

Kurita T,Mizumoto T.Facile and convenient method of deuterium gas generation using a Pd/C-catalyzed H2-D2 exchange reaction and its application to synthesis of deuterium-labeled compounds.Chemistry2008;14:3371-9

[26]

Sajiki H,Esaki H,Maegawa T.Complete replacement of H2 by D2 via Pd/C-catalyzed H/D exchange reaction.Org Lett2004;6:3521-3

[27]

Chandrasekhar S,Mahesh Chandra B,Naresh P.Flow chemistry approach for partial deuteration of alkynes: synthesis of deuterated taxol side chain.Tetrahedron Letters2011;52:3865-7

[28]

Jinno K,Nagoshi T.Microcolumn gel permeation chromatography with inductively coupled plasma emission spectrometric detection.Anal Chem1984;56:1977-9

[29]

Narayanam JM,Stephenson CR.Electron-transfer photoredox catalysis: development of a tin-free reductive dehalogenation reaction.J Am Chem Soc2009;131:8756-7

[30]

Wang X,Schuman DP.General and practical potassium methoxide/disilane-mediated dehalogenative deuteration of (hetero)arylhalides.J Am Chem Soc2018;140:10970-4

[31]

Ma H,Ding X,Ma C.Electrocatalytic dechlorination of chloropicolinic acid mixtures by using palladium-modified metal cathodes in aqueous solutions.Electrochimica Acta2016;210:762-72

[32]

Zhang B,Wang S.Electrocatalytic water-splitting for the controllable and sustainable synthesis of deuterated chemicals.Science Bulletin2021;66:562-9

[33]

Kurimoto A,Cao Y,Berlinguette CP.Electrolytic deuteration of unsaturated bonds without using D2.Nat Catal2020;3:719-26

[34]

Gütz C,Bucher C,Waldvogel SR.Development and scale-up of the electrochemical dehalogenation for the synthesis of a key intermediate for NS5A inhibitors.Org Process Res Dev2015;19:1428-33

[35]

Gütz C,Bänziger M.A novel cathode material for cathodic dehalogenation of 1,1-dibromo cyclopropane derivatives.Chemistry2015;21:13878-82

[36]

Liu C,Li M,Zhang B.Electrocatalytic deuteration of halides with D2O as the deuterium source over a copper nanowire arrays cathode.Angew Chem2020;132:18685-9

[37]

Xiong P,Song J,Li JF.Electrochemically enabled carbohydroxylation of alkenes with H2O and organotrifluoroborates.J Am Chem Soc2018;140:16387-91

[38]

Liu X,Qiu J,Li G.Chemical-reductant-free electrochemical deuteration reaction using deuterium oxide.Angew Chem2020;132:14066-71

[39]

Wu Y,Wang C,Zhang B.Selective transfer semihydrogenation of alkynes with H2O (D2O) as the H (D) source over a Pd-P cathode.Angew Chem2020;132:21356-61

[40]

Ou W,Zou R,Loh KP.Room-temperature palladium-catalyzed deuterogenolysis of carbon oxygen bonds towards deuterated pharmaceuticals.Angew Chem Int Ed Engl2021;60:6357-61

[41]

Chong X,Huang Y,Zhang B.Potential-tuned selective electrosynthesis of azoxy-, azo- and amino-aromatics over a CoP nanosheet cathode.Natl Sci Rev2020;7:285-95 PMCID:PMC8288891

[42]

Wang L,Beller M.Palladium‐catalyzed methylation of nitroarenes with methanol.Angew Chem2019;131:5471-5

[43]

Blaser H,Studer M.Selective catalytic hydrogenation of functionalized nitroarenes: an update.ChemCatChem2009;1:210-21

[44]

Kawamata Y,Liu Z.Scalable, electrochemical oxidation of unactivated C-H bonds.J Am Chem Soc2017;139:7448-51 PMCID:PMC5465511

[45]

Mészáros R,Ötvös SB,Fülöp F.Continuous-flow hydrogenation and reductive deuteration of nitriles: a simple access to α,α-dideutero amines.Chempluschem2019;84:1508-11

[46]

Root DK.Electrochemical behavior of selected imine derivatives, reductive carboxylation, α-amino acid synthesis.J Electrochem Soc1982;129:1231-6

[47]

Zuman P.Aspects of electrochemical behavior of aldehydes and ketones in protic media.Electroanalysis2006;18:131-40

[48]

Li H,Koh AL.Activating and optimizing MoS2 basal planes for hydrogen evolution through the formation of strained sulphur vacancies.Nat Mater2016;15:48-53

[49]

Zhang J,Guo H.Unveiling active sites for the hydrogen evolution reaction on monolayer MoS2.Adv Mater2017;29:1701955

[50]

Lin L,Yan C.Synergistic catalysis over iron-nitrogen sites anchored with cobalt phthalocyanine for efficient CO2 electroreduction.Adv Mater2019;31:e1903470

[51]

Guo C,Vasileff A.Rational design of electrocatalysts and photo(electro)catalysts for nitrogen reduction to ammonia (NH3) under ambient conditions.Energy Environ Sci2018;11:45-56

[52]

Wang J,Jin H,Wang Y.Non-noble metal-based carbon composites in hydrogen evolution reaction: fundamentals to applications.Adv Mater2017;29:1605838

[53]

Chen Z,Liu J.Cobalt single-atom-intercalated molybdenum disulfide for sulfide oxidation with exceptional chemoselectivity.Adv Mater2020;32:e1906437

[54]

Uchida Y,Compton RG.Sweep voltammetry with a semi-circular potential waveform: electrode kinetics.J Electroanal Chem2019;835:60-6

[55]

Wang H,Luber EJ.Redox flow batteries: how to determine electrochemical kinetic parameters.ACS Nano2020;14:2575-84

[56]

Boronat M,Corma A,Illas F.A molecular mechanism for the chemoselective hydrogenation of substituted nitroaromatics with nanoparticles of gold on TiO2 catalysts: a cooperative effect between gold and the support.J Am Chem Soc2007;129:16230-7

[57]

Liu C,Su C.Controllable deuteration of halogenated compounds by photocatalytic D2O splitting.Nat Commun2018;9:80 PMCID:PMC5758826

[58]

Zhang M,Zhu C.Deoxygenative deuteration of carboxylic acids with D2O.Angew Chem2019;131:318-22

[59]

Shinde GB,Deshmukh SP,Mathad VT.Industrial application of the forster reaction: novel one-pot synthesis of cinacalcet hydrochloride, a calcimimetic agent.Org Process Res Dev2011;15:455-61

[60]

Castell JV,Miranda MA.A general procedure for isotopic (deuterium) labelling of non-steroidal antiinflammatory 2-arylpropionic acids.J Label Compd Radiopharm1994;34:93-100

[61]

Hu Y,Wei W,Zhang X.A convenient synthesis of deuterium labeled amines and nitrogen heterocycles with KOt-Bu/DMSO-d6.Tetrahedron2015;71:1425-30

[62]

Shi R,Zhao Y.Room-temperature electrochemical acetylene reduction to ethylene with high conversion and selectivity.Nat Catal2021;4:565-74

[63]

Lee JH,Xie Z,Chen JG.Isotopic effect on electrochemical CO2 reduction activity and selectivity in H2O- and D2O-based electrolytes over palladium.Chem Commun (Camb)2019;56:106-8

[64]

Cui X,Chen R.Room-temperature electrochemical water-gas shift reaction for high purity hydrogen production.Nat Commun2019;10:86 PMCID:PMC6325145

[65]

Choi S,Haile SM.Protonic ceramic electrochemical cells for hydrogen production and electricity generation: exceptional reversibility, stability, and demonstrated faradaic efficiency.Energy Environ Sci2019;12:206-15

[66]

Pan H.Electrochemical CO2 reduction to methane with remarkably high Faradaic efficiency in the presence of a proton permeable membrane.Energy Environ Sci2020;13:3567-78

[67]

Zhou Y,Woods JM.Revealing the contribution of individual factors to hydrogen evolution reaction catalytic activity.Adv Mater2018;30:e1706076

[68]

Wang H,Lv Z,Lei A.Recent advances in oxidative R1-H/R2-H cross-coupling with hydrogen evolution via photo-/electrochemistry.Chem Rev2019;119:6769-87

[69]

Yu FY,Yin LY.Pt-O bond as an active site superior to Pt0 in hydrogen evolution reaction.Nat Commun2020;11:490 PMCID:PMC6981163

[70]

McAllister J,McGlynn JC.Tuning and mechanistic insights of metal chalcogenide molecular catalysts for the hydrogen-evolution reaction.Nat Commun2019;10:370 PMCID:PMC6342911

[71]

De Arquer FPG,Ozden A.CO2 electrolysis to multicarbon products at activities greater than 1 A cm-2.Science2020;367:661-6

[72]

Wakerley D,Ozanam F.Bio-inspired hydrophobicity promotes CO2 reduction on a Cu surface.Nat Mater2019;18:1222-7

[73]

Cao L,Hu E.Solvation structure design for aqueous Zn metal batteries.J Am Chem Soc2020;142:21404-9

[74]

Tang B,Liang S.Issues and opportunities facing aqueous zinc-ion batteries.Energy Environ Sci2019;12:3288-304

[75]

Kubota SR.Electrochemical oxidation of 5-hydroxymethylfurfural to 2,5-furandicarboxylic acid (FDCA) in acidic media enabling spontaneous FDCA separation.ChemSusChem2018;11:2138-45

[76]

Gandía LM,Ursúa A,Diéguez PM.Renewable hydrogen production:  performance of an alkaline water electrolyzer working under emulated wind conditions.Energy Fuels2007;21:1699-706

[77]

Zhang N,Tao L.Electrochemical oxidation of 5-hydroxymethylfurfural on nickel nitride/carbon nanosheets: reaction pathway determined by in situ sum frequency generation vibrational spectroscopy.Angew Chem2019;131:16042-50

[78]

Liu W,Xu Z,Jin S.Electrochemical oxidation of 5-hydroxymethylfurfural with nife layered double hydroxide (LDH) nanosheet catalysts.ACS Catal2018;8:5533-41

[79]

Dutta A.Ternary NiAuPt nanoparticles on reduced graphene oxide as catalysts toward the electrochemical oxidation reaction of ethanol.ACS Catal2015;5:1371-80

[80]

Liu D,Cai W.Selective photoelectrochemical oxidation of glycerol to high value-added dihydroxyacetone.Nat Commun2019;10:1779 PMCID:PMC6467901

[81]

Ren S,Salvatore D.Molecular electrocatalysts can mediate fast, selective CO2 reduction in a flow cell.Science2019;365:367-9

[82]

Leow WR,Ozden A.Chloride-mediated selective electrosynthesis of ethylene and propylene oxides at high current density.Science2020;368:1228-33

[83]

Mo Y,Rughoobur G.Microfluidic electrochemistry for single-electron transfer redox-neutral reactions.Science2020;368:1352-7

[84]

Peters BK,Reisberg SH.Scalable and safe synthetic organic electroreduction inspired by Li-ion battery chemistry.Science2019;363:838-45 PMCID:PMC7001862

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