SupportingInformation

for

Late-stageC–HDeuterationof(Hetero)ArenesviaDeuterium-BondingEnhancedRhenium

Catalysis

LiqunHu1,+,YaoXiang1,+,QingHuang1,HuiZhou2,*,andYouweiXie1,*

1HubeiKeyLaboratoryofBioinorganicChemistryandMateriaMedica;KeyLaboratoryofMaterialChemistryforEnergyConversionandStorage,MinistryofEducation;HubeiKeyLaboratoryofMaterialsChemistryandServiceFailure;SchoolofChemistryandChemicalEngineering,HuazhongUniversityofScienceandTechnology,1037LuoyuRoad,Wuhan430074,China

2CollegeofChemistry,CentralChinaNormalUniversity(CCNU),152LuoyuRoad,Wuhan430079,China

Theseauthorscontributeequallytothiswork.

CorrespondingAuthor

HuiZhouEmail:

huizhou@

;YouweiXieEmail:

xieyw@

TableofContents

1

Generalinformation

S2

2

TableS1Optimizationofthereactionconditionsa

S3

3

ProductsofDeuterationof(Hetero)Arenesandspectraldata

S4

4

Gramscaleexperimentandrecyclingdeuterationexperimentofsubstrate6

S68

5

Reactionintermediatesdetectedby1HNMR

S70

6

DFTresults

S72

7

Cartesiancoordinates

S72

8

NMRspectroscopicdata

S107

9

References

S175

S1

1Generalinformation

Re2O7andHFIP-d1werepurchasedfromSigmaAldrich.AcODandTFA-d1werepurchasedfromEnergychemicalcompany.OtherchemicalsusedinthismanuscriptwerepurchasedfromEnergychemicalcompany,BidePharmatechLtd,Inno-ChemLtd,AdamasCompany,AlfaAesarCompanyandCambridgeIsotopeLaboratories,Inc.Othercommerciallyavailablecompoundswereusedasprovidedwithoutfurtherpurification.Unlessotherwisenoted,allreactionswereperformedunderair.Reactionsweremonitoredbythinlayerchromatography(TLC)onsilicagelpre-coatedplasticsheets(0.2mm).VisualizationwasaccomplishedbyirradiationwithUVlightat254nmandKMnO4.Flashcolumnchromatographywasperformedoversilicagel(200-300mesh).1H-,13C-and19F-NMRspectrawererecordedonBrukerAV400orBrukerAscendTM600MHzatroomtemperature.ChemicalshiftswerereportedinppmonthescalerelativetoCDCl3(δ=7.26for1H-NMR,δ=77.00for13C-NMR)orCD3OD(δ=3.31for1H-NMR,δ=49.00for13C-NMR).Protonspectrumdescriptionanalysisisasfollows:chemicalshift(ppm),multipletanalysis(s=singlet,d=doublet,t=triplet,q=quartet,m=multiplet,tq=triplequartet,dp=doublepentet,h=sextet,hept=heptet,p=pentet),unidentifiedcouplingthemethodsareallanalyzedbymultiplepeakprocessing,andthecarbonspectrumisdescribedinppm.Couplingconstants(J)werereportedinHertz(Hz).Deuteriumincorporationpercentages(D%)weredeterminedbycomparingthe1HNMRintegralintensityundeuterated-Me,-OMegroupsorinertHsignal,andthedeuteratedpositionswerecheckedbycomparing1HNMRspectrumwithstartingmaterial.

S2

2TableS1Optimizationofthereactionconditionsa

Reactionswereperformedwith1(1.0equiv.),solventastheDsource(0.25–0.5M),attheindicatedtemperaturefor6hours,chemicalyieldsweredeterminedby1HNMRwithaninternalstandard.bTheratioofmixturesolventis1:1.

S3

3ProductsofDeuterationof(Hetero)Arenesandspectraldata

Generalsyntheticmethod:Toa10mLSchlenktubewasaddedaromatics(1-61)(1.0equiv.),Re2O7(1-5mol%),AcODorCF3CO2D(0.25M).Thereactionmixturewasstirredfor6hor12hat120℃(oilbath),thencooledtoroomtemperature,2mLDCMand2mLdistilledH2Owereaddedforextraction.Theorganiclayerwaswashedthreetimeswith2mLdistilledH2OforremovalofAcOH(D)orCF3CO2H(D),collectedandremovedunderreducedpressure.Thecrudemixturewasthenpurifiedbyflashcolumnchromatographytoaffordthetargetproduct.Deuterationrateanddeuterationsitesweredeterminedby1HNMR.ThedegreeofdeuteriumincorporationisdeterminedbyGC-MS,usingtheUniversalMassCalculator,accordingtotherecentliterature.1

Forsomesubstratesthatarevolatileanddifficulttoobtainaccurateseparationyields,thefollowingmethodswereused.Whenthereactioncooledtoroomtemperature,CH2Br2(7μL,0.10mmol)wasadded.Theresultingmixturewasdirectlyusedforcharacterization,andthespecificformulaisasfollows:

S4

1-Methoxy-4-methylbenzene-2,3,5,6-d4(1).

1wassynthesizedaccordingtothegeneralsyntheticmethodwith1’(43.37mg,0.355mmol),Re2O7(1.72mg,0.00355mmol),andAcOD(1.42mL),thencooledtoroomtemperature,2mLDCMand2mLdistilledH2Owereaddedforextraction.

Theorganiclayerwaswashedthreetimeswith2mLdistilledH2OforremovalofAcOH(D),collectedandremovedunderreducedpressure.Thecrudemixturewasthenpurifiedthroughflashchromatography(1-5%ethylacetate/petroleumether)togivethedesiredproductasacolorlessoil(42.1mg,97%yield).1HNMR(600MHz,CDCl3)δ7.11(s,1.68H,16%D),6.86–6.82(m,0.14H,93%D),3.80(s,3H),2.32(s,3H).13CNMR(151MHz,CDCl3)δ157.6–157.2(m),129.9–129.6(m),113.8–113.1(m),55.2,20.4.GC-MSanalysisofthedeuterationproduct:Highestpeak:124.08(1-d2).Moredetailsfordeuterationwereshownasthefollowing.

S5

Anisole-2,4,6-d3(2).

2wassynthesizedaccordingtothegeneralsyntheticmethodwith2’(60.89mg,0.563mmol),Re2O7(2.73mg,0.00563mmol),andAcOD(2.25mL),thencooledtoroomtemperature,CH2Br2(7μL,0.10mmol)wasadded.Theresultingmixturewas

directlyusedforcharacterization.Thechemicalyieldwasdeterminedincrudemixtureby1HNMRwithCH2Br2(96%1HNMRyield).1HNMR(400MHz,Chloroform-d)δ7.26(s,2H),6.94–6.92(t,J

7.3Hz,0.05H,95%D),6.89–6.87(d,J=8.7Hz,0.16H,92%D),3.78(s,3H).GC-MSanalysisofthedeuterationproduct:Highestpeak:111.08(2-d3).Moredetailsfordeuterationwereshownasthefollowing.

S6

1-Ethyl-4-methoxybenzene-2,3,5,6-d4(3).

3wassynthesizedaccordingtothegeneralsyntheticmethodwith3’(54.5mg,0.40mmol),Re2O7(1.94mg,0.0040mmol),andAcOD(1.60mL),thencooledtoroomtemperature,2mLDCMand2mLdistilledH2Owereaddedforextraction.Theorganiclayerwaswashedthreetimeswith2mLdistilledH2Oforremovalof

AcOH(D),collectedandremovedunderreducedpressure.Thecrudemixturewasthenpurifiedthroughflashchromatography(1-5%ethylacetate/petroleumether)togivethedesiredproductasacolorlessoil(51.7mg,95%yield).1HNMR(600MHz,CDCl3)δ7.14(s,1.78H,11%D),6.86(d,J=8.8Hz,0.12H,94%D),3.81(s,3H),2.62(q,J=7.6Hz,2H),1.24(t,J=7.5Hz,3H).13CNMR(151MHz,CDCl3)δ157.5,136.3,128.8–128.4(m),113.8–113.2(m),55.2,28.0,15.9.GC-MSanalysisofthedeuterationproduct:Highestpeak:138.10(3-d2).Moredetailsfordeuterationwereshownasthefollowing.

S7

4-Methoxy-1,2-dimethylbenzene-3,5,6-d3(4).

4wassynthesizedaccordingtothegeneralsyntheticmethodwith4’(69.16mg,0.508mmol),Re2O7(2.46mg,0.00508mmol),andAcOD(2.03mL),thencooledtoroomtemperature,2mLDCMand2mLdistilledH2Owereaddedfor

extraction.Theorganiclayerwaswashedthreetimeswith2mLdistilledH2OforremovalofAcOH(D),collectedandremovedunderreducedpressure.Thecrudemixturewasthenpurifiedthroughflashchromatography(1-5%ethylacetate/petroleumether)togivethedesiredproductasacolorlessoil(65.7mg,95%yield).1HNMR(600MHz,CDCl3)δ7.06(s,0.86H,14%D),6.74(s,0.06H,94%D),6.68(d,J=8.2Hz,0.06H,94%D),3.83–3.77(m,3H),2.27(s,3H),2.22(s,3H).13CNMR(151MHz,CDCl3)δ157.8–157.4(m),138.0–137.4(m),130.7–130.0(m),128.5,115.6–114.8(m),110.8–110.1(m),55.2,20.0,18.7.GC-MSanalysisofthedeuterationproduct:Highestpeak:138.09(4-d2).Moredetailsfordeuterationwereshownasthefollowing.

S8

1-Methoxy-3,5-dimethylbenzene-2,4,6-d3(5).

5wassynthesizedaccordingtothegeneralsyntheticmethodwith5’(48.63mg,0.3571mmol),Re2O7(1.73mg,0.00357mmol),andAcOD(1.43mL),thencooledtoroomtemperature,2mLDCMand2mLdistilledH2Owereaddedforextraction.Theorganiclayerwaswashedthreetimeswith2mLdistilledH2Ofor

removalofAcOH(D),collectedandremovedunderreducedpressure.Thecrudemixturewasthenpurifiedthroughflashchromatography(1-5%ethylacetate/petroleumether)togivethedesiredproductasacolorlessoil(46.2mg,95%yield).1HNMR(600MHz,CDCl3)δ6.63(s,0.09H,91%D),6.57(s,0.18H,91%D),3.80(s,3H),2.32(s,6H).13CNMR(151MHz,CDCl3)δ159.6–159.4(m),139.3–138.8(m),122.5–121.8(m),111.7–111.0(m),55.0,21.4–21.2(m).GC-MSanalysisofthedeuterationproduct:Highestpeak:139.11(5-d3).Moredetailsfordeuterationwereshownasthefollowing.

S9

1,4-Dimethoxybenzene-2,3,5,6-d4(6).

6wassynthesizedaccordingtothegeneralsyntheticmethodwith6’(66.7mg,0.483mmol),Re2O7(2.34mg,0.00483mmol),andAcOD(1.94mL),thencooledtoroomtemperature,2mLDCMand2mLdistilledH2Owereaddedforextraction.

Theorganiclayerwaswashedthreetimeswith2mLdistilledH2OforremovalofAcOH(D),collectedandremovedunderreducedpressure.Thecrudemixturewasthenpurifiedthroughflashchromatography(1-5%ethylacetate/petroleumether)togivethedesiredproductasawhitesolid(65.4mg,98%yield).1HNMR(600MHz,CDCl3)δ6.85(s,0.65H,84%D),3.77(s,6H).13CNMR(151MHz,CDCl3)δ154.0–153.6(m),114.7–114.0(m),55.7.GC-MSanalysisofthedeuterationproduct:Highestpeak:142.09(6-d4).Moredetailsfordeuterationwereshownasthefollowing.

S10

1,3-Dimethoxy-5-methylbenzene-2,4,6-d3(7).

7wassynthesizedaccordingtothegeneralsyntheticmethodwith7’(39.6mg,0.26mmol),Re2O7(1.26mg,0.0026mmol),andAcOD(1.10mL),thencooledtoroomtemperature,2mLDCMand2mLdistilledH2Owereaddedforextraction.Theorganiclayerwaswashedthreetimeswith2mLdistilledH2Oforremovalof

AcOH(D),collectedandremovedunderreducedpressure.Thecrudemixturewasthenpurifiedthroughflashchromatography(1-5%ethylacetate/petroleumether)togivethedesiredproductasacolorlessoil(38.0mg,96%yield).1HNMR(600MHz,CDCl3)δ6.35(s,0.36H,82%D),6.30(s,0.10H,90%D),3.78(s,6H),2.32(s,3H).13CNMR(151MHz,CDCl3)δ160.7–160.5(m),140.2–139.9(m),107.2

–106.5(m),97.5–96.9(m),55.2,21.8–21.5(m).GC-MSanalysisofthedeuterationproduct:Highestpeak:155.12(7-d3).Moredetailsfordeuterationwereshownasthefollowing.

S11

1,2-Dimethoxy-4-methylbenzene-3,5,6-d3(8).

8wassynthesizedaccordingtothegeneralsyntheticmethodwith8’(122.2mg,0.803mmol),Re2O7(3.89mg,0.00803mmol),andAcOD(3.20mL),thencooledtoroomtemperature,2mLDCMand2mLdistilledH2Owereaddedforextraction.

Theorganiclayerwaswashedthreetimeswith2mLdistilledH2OforremovalofAcOH(D),collectedandremovedunderreducedpressure.Thecrudemixturewasthenpurifiedthroughflashchromatography(1-5%ethylacetate/petroleumether)togivethedesiredproductasacolorlessoil(114.9mg,94%yield).1HNMR(600MHz,CDCl3)δ6.77(s,0.10H,90%D),6.70(s,0.16H,92%D),3.86(s,3H),3.85(s,3H),2.30(s,3H).13CNMR(151MHz,CDCl3)δ148.6,146.7,130.3–130.1(m),120.8–120.1(m),112.4–111.8(m),111.2–110.5(m),55.9,55.7,20.9–20.7(m).GC-MSanalysisofthedeuterationproduct:Highestpeak:155.11(8-d3).Moredetailsfordeuterationwereshownasthefollowing.

S12

1,3,5-Trimethoxybenzene-2,4,6-d3(9).

9wassynthesizedaccordingtothegeneralsyntheticmethodwith9’(104.16mg,0.619mmol),Re2O7(3.0mg,0.00619mmol),andAcOD(2.50mL),thencooledtoroomtemperature,2mLDCMand2mLdistilledH2Owereaddedforextraction.Theorganiclayerwaswashedthreetimeswith2mLdistilledH2Ofor

removalofAcOH(D),collectedandremovedunderreducedpressure.Thecrudemixturewasthenpurifiedthroughflashchromatography(1-5%ethylacetate/petroleumether)togivethedesiredproductasalightredsolid(95.8mg,92%yield).1HNMR(600MHz,CDCl3)δ6.09(s,0.18H,91%D),3.77(s,3H).13CNMR(151MHz,CDCl3)δ161.5–161.3(m),93.0–92.4(m),55.3.GC-MSanalysisofthedeuterationproduct:Highestpeak:171.09(9-d3).Moredetailsfordeuterationwereshownasthefollowing.

S13

1,2,4-Trimethoxybenzene-3,5,6-d3(10).

10wassynthesizedaccordingtothegeneralsyntheticmethodwith10’(25.7mg,0.152mmol),Re2O7(0.74mg,0.00152mmol),andAcOD(0.61mL),thencooledtoroomtemperature,2mLDCMand2mLdistilledH2Owereaddedfor

extraction.Theorganiclayerwaswashedthreetimeswith2mLdistilledH2OforremovalofAcOH(D),collectedandremovedunderreducedpressure.Thecrudemixturewasthenpurifiedthroughflashchromatography(1-5%ethylacetate/petroleumether)togivethedesiredproductasacolorlessoil(25.6mg,80%yield).1HNMR(600MHz,CDCl3)δ6.80–6.76(m,0.18H,82%D),6.51(s,0.10H,90%D),6.42–6.37(m,0.20H,80%D),3.85(s,3H),3.83(s,3H),3.77(s,3H).13CNMR(151MHz,CDCl3)δ154.2–154.1(m),149.7,143.4–143.3(m),111.8–111.1(m),102.9–102.1(m),100.4–99.8(m),56.4,55.8,55.6.GC-MSanalysisofthedeuterationproduct:Highestpeak:171.10(10-d3).Moredetailsfordeuterationwereshownasthefollowing.

S14

1,2,3-Trimethoxy-5-methylbenzene-4,6-d2(11).

11wassynthesizedaccordingtothegeneralsyntheticmethodwith11’(47.77mg,0.262mmol),Re2O7(1.27mg,0.00262mmol),andAcOD(1.10mL),thencooledtoroomtemperature,2mLDCMand2mLdistilledH2Owereaddedfor

extraction.Theorganiclayerwaswashedthreetimeswith2mLdistilledH2OforremovalofAcOH(D),collectedandremovedunderreducedpressure.Thecrudemixturewasthenpurifiedthroughflashchromatography(5-10%ethylacetate/petroleumether)togivethedesiredproductasawhitesolid(45.4mg,95%yield).1HNMR(600MHz,CDCl3)δ6.39(s,0.27H,86%D),3.84(s,6H),3.81(s,3H),2.31(s,3H).13CNMR(151MHz,CDCl3)δ152.9,135.6,134.0–132.7(m),106.5–104.8(m),60.8,55.9,22.0–21.4(m).GC-MSanalysisofthedeuterationproduct:Highestpeak:184.12(11-d2).Moredetailsfordeuterationwereshownasthefollowing.

S15

p-Cresol-2,3,5,6-d4(12).

12wassynthesizedaccordingtothegeneralsyntheticmethodwith12’(22.1mg,0.204mmol),Re2O7(0.99mg,0.00204mmol),andAcOD(0.82mL),thencooledtoroomtemperature,2mLDCMand2mLdistilledH2Owereaddedfor

extraction.Theorganiclayerwaswashedthreetimeswith2mLdistilledH2OforremovalofAcOH(D),collectedandremovedunderreducedpressure.Thecrudemixturewasthenpurifiedthroughflashchromatography(5-10%ethylacetate/petroleumether)togivethedesiredproductasawhitesolid(18.1mg,82%yield).1HNMR(600MHz,CDCl3)δ7.04(s,1.91H,4%D),6.76–6.72(m,0.14H,93%D),4.78(s,0.91H),2.28(s,3H).13CNMR(151MHz,CDCl3)δ153.1,130.1–129.8(m),115.1–114.5(m),20.5.GC-MSanalysisofthedeuterationproduct:Highestpeak:110.08(12-d2).Moredetailsfordeuterationwereshownasthefollowing.

S16

2,6-Dimethylphen-3,4,5-d3-ol(13).

13wassynthesizedaccordingtothegeneralsyntheticmethodwith13’(60.5mg,0.495mmol),Re2O7(2.40mg,0.00495mmol),andAcOD(1.98mL),thencooledtoroomtemperature,2mLDCMand2mLdistilledH2Owereaddedforextraction.Theorganiclayerwaswashedthreetimeswith2mLdistilledH2Oforremovalof

AcOH(D),collectedandremovedunderreducedpressure.Thecrudemixturewasthenpurifiedthroughflashchromatography(5-10%ethylacetate/petroleumether)togivethedesiredproductasawhitesolid(54.4mg,90%yield).1HNMR(600MHz,CDCl3)δ6.99(s,1.56H,22%D),6.77(t,J=7.4Hz,0.09H,91%D),4.64(bs,0.88H),2.26(s,6H).13CNMR(151MHz,CDCl3)δ152.1,128.8–128.2(m),123.2–122.7(m),120.3–119.4(m),15.9–15.7(m).GC-MSanalysisofthedeuterationproduct:

Highestpeak:123.08(13-d).Moredetailsfordeuterationwereshownasthefollowing.

S17

2-Methoxy-4-methylphen-3,5,6-d3-ol(14).

14wassynthesizedaccordingtothegeneralsyntheticmethodwith14’(65.6mg,0.474mmol),Re2O7(2.30mg,0.00474mmol),andAcOD(1.90mL),thencooledtoroomtemperature,2mLDCMand2mLdistilledH2Owereaddedfor

extraction.Theorganiclayerwaswashedthreetimeswith2mLdistilledH2OforremovalofAcOH(D),collectedandremovedunderreducedpressure.Thecrudemixturewasthenpurifiedthroughflashchromatography(5-10%ethylacetate/petroleumether)togivethedesiredproductasacolorlessoil(55.7mg,85%yield).1HNMR(600MHz,CDCl3)δ6.84(s,0.09H,91%D),6.70(s,0.10H,90%D),6.68(s,0.09H,91%D),5.55(s,1H),3.87(s,3H),2.31(s,3H).13CNMR(151MHz,CDCl3)δ146.2,143.2,129.4,121.3–120.9(m),114.0–113.6(m),111.6–111.2(m),55.8,20.9.GC-MSanalysisofthedeuterationproduct:Highestpeak:141.09(14-d3).Moredetailsfordeuterationwereshownasthefollowing.

S18

1-Fluoro-3,5-dimethoxybenzene-2,4,6-d3(15).

15wassynthesizedaccordingtothegeneralsyntheticmethodwith15’(102.0mg,0.654mmol),Re2O7(3.17mg,0.00654mmol),andAcOD(2.62mL),thencooledtoroomtemperature,2mLDCMand2mLdistilledH2Owereaddedforextraction.Theorganiclayerwaswashedthreetimeswith2mLdistilledH2Ofor

removalofAcOH(D),collectedandremovedunderreducedpressure.Thecrudemixturewasthenpurifiedthroughflashchromatography(1-5%ethylacetate/petroleumether)togivethedesiredproductasacolorlessoil(97.9mg,96%yield).1HNMR(600MHz,CDCl3)δ6.25(s,0.16H,92%D),6.23(s,0.08H,92%D),3.77(s,6H).13CNMR(151MHz,CDCl3)δ164.1(d,J=242.8Hz),161.7–161.1(m),96.4–95.8(m),94.3–93.6(m),55.4.19FNMR(565MHz,CDCl3)δ-111.28–-111.73(m).GC-MSanalysisofthedeuterationproduct:Highestpeak:159.08(15-d3).Moredetailsfordeuterationwereshownasthefollowing.

S19

4-Chloro-2-methoxy-1-methylbenzene-3,5,6-d3(16).

16wassynthesizedaccordingtothegeneralsyntheticmethodwith16’(34.37mg,0.220mmol),Re2O7(3.19mg,0.0066mmol),andAcOD(0.878mL),thencooledtoroomtemperature,2mLDCMand2mLdistilledH2Owereaddedforextraction.Theorganiclayerwaswashedthreetimeswith2mLdistilledH2Ofor

removalofAcOH(D),collectedandremovedunderreducedpressure.Thecrudemixturewasthenpurifiedthroughflashchromatography(1-5%ethylacetate/petroleumether)togivethedesiredproductasacolorlessoil(32.6mg,95%yield).1HNMR(600MHz,CDCl3)δ7.04(s,0.88H,12%D),6.84(d,J=7.9Hz,0.09H,91%D),6.81(s,0.15H,85%D),3.82(s,3H),2.18(s,3H).13CNMR(151MHz,CDCl3)δ158.1,132.0–131.5(m),131.2–130.8(m),125.1,120.3–119.4(m),111.0–110.0(m),55.4,15.7.GC-MSanalysisofthedeuterationproduct:Highestpeak:158.04(16-d2).Moredetailsfordeuterationwereshownasthefollowing.

S20

1-Bromo-2,4-dimethoxybenzene-3,5,6-d3(17).

17wassynthesizedaccordingtothegeneralsyntheticmethodwith17’(92.8mg,0.427mmol),Re2O7(2.07mg,0.00427mmol),andAcOD(1.71mL),thencooledtoroomtemperature,2mLDCMand2mLdistilledH2Owereaddedfor

extraction.Theorganiclayerwaswashedthreetimeswith2mLdistilledH2OforremovalofAcOH(D),collectedandremovedunderreducedpressure.Thecrudemixturewasthenpurifiedthroughflashchromatography(1-5%ethylacetate/petroleumether)togivethedesiredproductasacolorlessoil(80.7mg,87%yield).1HNMR(600MHz,CDCl3)δ7.40(s,0.92H,8%D),6.48(s,0.08H,92%D),6.41–6.37(m,0.09H,91%D),3.86(d,J=1.8Hz,3H),3.79(d,J=1.8Hz,3H).13CNMR(151MHz,CDCl3)δ160.1,156.4,133.8–132.5(m),106.1–105.3(m),102.3,100.1–99.3(m),56.1,55.5.GC-MSanalysisofthedeuterationproduct:Highestpeak:218.02(17-d2).Moredetailsfordeuterationwereshownasthefollowing.

S21

1-Fluoro-4-methoxybenzene-2,3,5,6-d4(18).

18wassynthesizedaccordingtothegeneralsyntheticmethodwith18’(64.6mg,0.512mmol),Re2O7(2.48mg,0.00512mmol),andCF3CO2D(2.1mL)for12hours,thencooledtoroomtemperature,2mLDCMand2mLdistilledH2Owereaddedfor

extraction.Theorganiclayerwaswashedthreetimeswith2mLdistilledH2OforremovalofCF3CO2H(D),collectedandremovedunderreducedpressure.Thecrudemixturewasthenpurifiedthroughflashchromatography(1-5%ethylacetate/petroleumether)togivethedesiredproductasacolorlessoil(59.4mg,92%yield).1HNMR(600MHz,CDCl3)δ6.98(d,J=8.2Hz,1.74H,13%D),6.85–6.81(m,0.20H,90%D),3.78(s,3H).13CNMR(151MHz,CDCl3)δ157.2(d,J=236.5Hz),155.6(d,J=7.0Hz),115.6(d,J=23.1Hz),114.7(dd,J=20.9,7.8Hz),114.4(dd,J=24.7,8.4Hz),55.7.19FNMR(565MHz,CDCl3)δ-124.37–-124.48(m).GC-MSanalysisofthedeuterationproduct:Highestpeak:128.06(18-d2).Moredetailsfordeuterationwereshownasthefollowing.

S22

1-Chloro-3-methoxybenzene-2,4,5,6-d4(19).

19wassynthesizedaccordingtothegeneralsyntheticmethodwith19’(54.75mg,0.384mmol),Re2O7(1.86mg,0.00384mmol),andCF3CO2D(1.54mL)for12hours,thencooledtoroomtemperature,2mLDCMand2mLdistilledH2Owereaddedforextraction.Theorganiclayerwaswashedthreetimeswith2mL

distilledH2OforremovalofCF3CO2H(D),collectedandremovedunderreducedpressure.Thecrudemixturewasthenpurifiedthroughflashchromatography(1-5%ethylacetate/petroleumether)togivethedesiredproductasacolorlessoil(50.9mg,93%yield).1HNMR(400MHz,CDCl3)δ7.20(s,0.90H,10%D),6.93(d,J=7.9Hz,0.16H,84%D),6.90(s,0.10H,90%D),6.80(d,J=8.4Hz,0.15H,85%D),3.80(s,3H).13CNMR(101MHz,CDCl3)δ160.8–159.7(m),134.7(d,J=13.3Hz),130.0(d,J=17.2Hz),114.4–113.7(m),112.7–112.0(m),55.4.GC-MSanalysisofthedeuterationproduct:Highestpeak:145.03(19-d3).Moredetailsfordeuterationwereshownasthefollowing.

S23

1-Bromo-4-methoxybenzene-2,3,5,6-d4(20).

20wassynthesizedaccordingtothegeneralsyntheticmethodwith20’(97.26mg,0.52mmol),Re2O7(2.52mg,0.0052mmol),andCF3CO2D(2.08mL)for12hours,thencooledtoroomtemperature,2mLDCMand2mLdistilledH2Owere

addedforextraction.Theorganiclayerwaswashedthreetimeswith2mLdistilledH2OforremovalofCF3CO2H(D),collectedandremovedunderreducedpressure.Thecrudemixturewasthenpurifiedthroughflashchromatography(1-5%ethylacetate/petroleumether)togivethedesiredproductasacolorlessoil(92.4mg,95%yield).1HNMR(400MHz,CDCl3)δ7.38(s,1.82H,9%D),6.81–6.76(m,0.10H,95%D),3.78(s,3H).13CNMR(101MHz,CDCl3)δ158.7–158.4(m),132.2–132.0(m),116.2–114.8(m),112.7,55.4.GC-MSanalysisofthedeuterationproduct:Highestpeak:187.98(20-d2).Moredetailsfordeuterationwereshownasthefollowing.

S24

2-Bromo-4-fluoro-1-methoxybenzene-3,5,6-d3(21).

21wassynthesizedaccordingtothegeneralsyntheticmethodwith21’(40.21mg,0.196mmol),Re2O7(0.95mg,0.00196mmol),andCF3CO2D(0.78mL)for12hours,thencooledtoroomtemperature,2mLDCMand2mLdistilledH2O

wereaddedforextraction.Theorganiclayerwaswashedthreetimeswith2mLdistilledH2OforremovalofCF3CO2H(D),collectedandremovedunderreducedpressure.Thecrudemixturewasthenpurifiedthroughflashchromatography(1-5%ethylacetate/petroleumether)togivethedesiredproductasacolorlessoil(38.2mg,95%yield).1HNMR(600MHz,CDCl3)δ7.33–7.27(m,0.88H,12%D),7.02–6.95(m,0.85H,15%D),6.86–6.81(m,0.10H,90%D),3.86(s,3H).13CNMR(151MHz,CDCl3)δ156.5(d,J=242.5Hz),152.6–152.4(m),120.4(d,J=25.9Hz),114.8–114.4(m),112.3–111.9(m),111.9–111.5(m),56.7.19FNMR(565MHz,CDCl3)δ-122.04–-122.28(m).GC-MSanalysisofthedeuterationproduct:Highestpeak:204.95(21-d).Moredetailsfordeuterationwereshownasthefollowing.

S25

P-Xylene-2,3,5,6-d4(22).

22wassynthesizedaccordingtothegeneralsyntheticmethodwith22’(42.90mg,0.404mmol),Re2O7(1.96mg,0.00404mmol),andCF3CO2D(1.62mL)for6hours,aftercoolingtoroomtemperature,CH2Br2(7μL,0.1mmol)wasadded.Theresulting

mixturewasdirectlyusedforcharacterization.Thechemicalyieldwasdeterminedincrudemixtureby1HNMRwithCH2Br2(99%1HNMRyield).1HNMR(400MHz,Chloroform-d)δ7.07(s,0.40H,90%D),2.31(s,6H).GC-MSanalysisofthedeuterationproduct:Highestpeak:110.10(22-d4).Moredetailsfordeuterationwereshownasthefollowing.

S26

1,3,5-Trimethylbenzene-2,4,6-d3(23).

23wassynthesizedaccordingtothegeneralsyntheticmethodwith23’(100.0mg,0.836mmol),Re2O7(4.05mg,0.00836mmol),andAcOD(3.35mL),thencooledtoroomtemperature,2mLDCMand2mLdistilledH2Owereaddedfor

extraction.Theorganiclayerwaswashedthreetimeswith2mLdistilledH2OforremovalofAcOH(D),collectedandremovedunderreducedpressurecarefully.Theresidualmixturewasdirectlyusedforcharacterization.Thechemicalyieldwasdeterminedincrudemixtureby1HNMRwithCH2Br2(97%1HNMRyield).1HNMR(600MHz,CDCl3)δ6.88(s,0.21H,93%D),2.35(s,9H).13CNMR(151MHz,CDCl3)δ137.9–137.3(m),127.2–126.2(m),21.1.GC-MSanalysisofthedeuterationproduct:Highestpeak:123.11(23-d3).Moredetailsfordeuterationwereshownasthefollowing.

S27

1,2,3,5-Tetramethylbenzene-4,6-d2(24).

24wassynthesizedaccordingtothegeneralsyntheticmethodwith24’(34.08mg,0.254mmol),Re2O7(1.23mg,0.00254mmol),andAcOD(1.02mL),thencooledtoroomtemperature,2mLDCMand2mLdistilledH2Owereaddedfor

extraction.Theorganiclayerwaswashedthreetimeswith2mLdistilledH2OforremovalofAcOH(D),collectedandremovedunderreducedpressure.Thecrudemixturewasthenpurifiedthroughflashchromatography(100%petroleumether)togivethedesiredproductasacolorlessoil(27.9mg,82%yield).1HNMR(600MHz,CDCl3)δ6.91(s,0.16H,92%D),2.33(s,9H),2.21(s,3H).13CNMR(151MHz,CDCl3)δ136.3–135.9(m),134.6–134.2(m),131.7,128.6–127.4(m),20.7–20.6(m),20.5–20.3(m),14.9.GC-MSanalysisofthedeuterationproduct:Highestpeak:136.12(24-d2).Moredetailsfordeuterationwereshownasthefollowing.

S28

1,2,3,4,5-Pentamethylbenzene-6-d1(25).

25wassynthesizedaccordingtothegeneralsyntheticmethodwith25’(41.0mg,0.276mmol),Re2O7(1.34mg,0.00276mmol),andAcOD(1.1mL),thencooledtoroomtemperature,2mLDCMand2mLdistilledH2Owereaddedforextraction.Theorganiclayerwaswashedthreetimeswith