Iron-mediated C-H coupling of arenes and unactivated terminal alkenes directed by sulfur

Article abstract of DOI:10.1039/c5cc02676h

A sulfur-directed Fe(iii)-mediated ortho C-H coupling of arenes with unactivated terminal alkenes gives products of regioselective alkene chloroarylation. The novel mechanism involves redox-activation of the arene partner and alkene addition to the result

Full text of DOI:10.1039/c5cc02676h

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DOI: 10.1039/C5CC02676H
JournalꢀNameꢀ
COMMUNICATIONꢀ
ꢀ
Iron‐MediatedꢀC‐HꢀCouplingꢀofꢀArenesꢀandꢀUnactivatedꢀTerminalꢀ
AlkenesꢀDirectedꢀbyꢀSulfurꢀꢀ
CraigꢀW.ꢀCavanagh,aꢀMilesꢀH.ꢀAukland,aꢀAlanꢀHennessy,bꢀandꢀDavidꢀJ.ꢀProcter*a
Receivedꢀ00thꢀJanuaryꢀ20xx,ꢀ
Acceptedꢀ00thꢀJanuaryꢀ20xxꢀ
DOI:ꢀ10.1039/x0xx00000xꢀ
www.rsc.org/ꢀ
aldehydes,ꢀketones,ꢀestersꢀandꢀamides),ꢀlateꢀtransitionꢀmetalsꢀ
(e.g.ꢀ Pd,ꢀ Ru,ꢀ Rh)ꢀ andꢀ reactiveꢀ alkenesꢀ suchꢀ asꢀ acrylatesꢀ andꢀ
styrenes.3ꢀDespiteꢀtheꢀplethoraꢀofꢀdirectingꢀgroupsꢀstudied,ꢀtheꢀ
useꢀofꢀaꢀsulfurꢀsubstituentꢀonꢀanꢀaromaticꢀringꢀtoꢀmediateꢀC‐Hꢀ
couplingꢀ withꢀ alkenesꢀ hasꢀ onlyꢀ recentlyꢀ beenꢀ developedꢀ
(Schemeꢀ 1A).4ꢀ Theꢀ needꢀ toꢀ shiftꢀ towardsꢀ theꢀ useꢀ ofꢀ
inexpensiveꢀ firstꢀ rowꢀ transitionꢀ metalsꢀ forꢀ cross‐couplingꢀ
processes,ꢀ includingꢀ thoseꢀ involvingꢀ C‐Hꢀ functionalisation,ꢀ isꢀ
wellꢀappreciated.5ꢀDueꢀtoꢀtheꢀlowꢀcostꢀandꢀlowꢀtoxicityꢀofꢀironꢀ
andꢀitsꢀhighꢀnaturalꢀabundance,ꢀiron‐basedꢀreagentsꢀareꢀidealꢀ
candidatesꢀforꢀtheꢀdevelopmentꢀofꢀsuchꢀprocesses.
A sulfur-directed Fe(III)-mediated ortho C- H coupling of
arenes with unactivated terminal alkenes gives products of
regioselective
alkene
chloroarylation.
The
novel
mechanism involves redox-activation of the arene partner
and alkene addition to the resultant aryl radical cation.
Theꢀ useꢀ ofꢀ metalsꢀ toꢀ carryꢀ outꢀ C‐Hꢀ functionalisationꢀ inꢀ
aromaticꢀsubstratesꢀisꢀhighlyꢀdesirableꢀdueꢀtoꢀfavourableꢀstepꢀ
andꢀ atomꢀ economy.1ꢀ Asꢀ regioselectiveꢀ C‐Hꢀ functionalisationꢀ
canꢀ oftenꢀ proveꢀ difficult,ꢀ directingꢀ groupsꢀ areꢀ usedꢀ toꢀ
facilitateꢀ functionalisationꢀ withꢀ directedꢀ orthoꢀ C‐Hꢀ bondꢀ
activationꢀ onꢀ anꢀ aromaticꢀ orꢀ heteroaromaticꢀ ringꢀ beingꢀ aꢀ
commonꢀ approach.2ꢀ Inꢀ recentꢀ years,ꢀ thereꢀ hasꢀ beenꢀ greatꢀ
interestꢀinꢀtheꢀmetal‐catalysedꢀorthoꢀC‐Hꢀcouplingꢀofꢀarenesꢀ
andꢀheteroarenesꢀwithꢀalkenes.ꢀ
Tableꢀ1ꢀOptimisationꢀofꢀFe(III)‐mediatedꢀC‐Hꢀarene/alkeneꢀcouplinga
ꢀ
MeO
Entry
SPh
MeO
SPh
Cl
reagent
C6H13
+
solvent, rt
1.5 h
C6H13
! A. Pt group metal-mediated, sulfur-directed C-H arene/alkene coupling
OMe 1a
2a
OMe
S(O)R
H
S(O)R
Oxidant
(equiv.)
Octene Solvent
(equiv.)
Atmosphere Conversion
(%)
Yield
(%)a
EWG/Ar
Rh(II), Pd(II)
EWG/Ar
MeCN
THF
N2
N2
55
0
10
0
1
FeCl3 (2.2)
FeCl3 (2.2)
10
10
2
! B. This work: Fe-mediated, sulfur-directed C-H arene/alkene coupling
N2
3
FeCl3 (2.2)
FeCl3 (2.2)
10
10
CH2Cl2
MeNO2
91
36
SAr
H
SAr
Cl
N2
N2
N2
N2
O2
air
4
60
13
63
0
14
4
Alkyl
Fe(III), rt
5
FeCl3.6H2O (2.2) 10
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
6b
7
FeBr3 (2.2)
Fe(acac)3 (2.2)
FeCl3 (2.2)
FeCl3 (2.2)
10
10
10
10
22
0
Alkyl
–via
SAr
H
!Novel redox-activated cross-coupling
!Simple, unactivated terminal alkenes
!Inexpensive Fe(III) reagent
8
88
88
47
49
9
10
11
12
FeCl3 (2.2)
FeCl3 (2.2)
FeCl3 (1)
5
2
CH2Cl2
CH2Cl2
CH2Cl2
air
air
air
85
81
48
45
37
25
Schemeꢀ1ꢀ
10
Thisꢀhasꢀbeenꢀachievedꢀusingꢀaꢀrangeꢀofꢀdirectingꢀgroupsꢀ(e.g.ꢀ
13c
14c
FeCl3 (2.2)
FeCl3 (4)
5
5
CH2Cl2/MeNO2 air
CH2Cl2/MeNO2 air
66
98
42
70
a. SchoolꢀofꢀChemistry,ꢀUniversityꢀofꢀManchester,ꢀOxfordꢀRoad,ꢀManchester,ꢀM13ꢀ
9PL,ꢀUnitedꢀKingdom.ꢀ
TypicalꢀConditions:ꢀOxidantꢀaddedꢀtoꢀaꢀmixtureꢀofꢀ1aꢀ(0.2ꢀmmol)ꢀandꢀocteneꢀandꢀ
stirredꢀforꢀ1.5ꢀh.ꢀaꢀYieldsꢀbyꢀNMRꢀspectroscopy.ꢀbꢀTheꢀbromideꢀanalogueꢀofꢀ2aꢀwasꢀ
obtained.ꢀ cꢀ FeCl3ꢀ inꢀ MeNO2ꢀ wasꢀ addedꢀ dropwiseꢀ toꢀ theꢀ sulfideꢀ andꢀ alkeneꢀ inꢀ
CH2Cl2.ꢀ
b. Syngenta,ꢀJealott'sꢀHillꢀInternationalꢀResearchꢀCentre,ꢀBracknell,ꢀBerkshire,ꢀRG42ꢀ
6EY,ꢀUnitedꢀKingdomꢀ
†ꢀAdditionalꢀexperiments,ꢀfullꢀexperimentalꢀdetailsꢀforꢀtheꢀpreparationꢀofꢀ
compounds,ꢀ1Hꢀandꢀ13CꢀNMRꢀspectraꢀforꢀnewꢀcompounds.ꢀSeeꢀ
DOI:ꢀ10.1039/x0xx00000xꢀ
Thisꢀjournalꢀisꢀ©ꢀTheꢀRoyalꢀSocietyꢀofꢀChemistryꢀ20xxꢀ
J.ꢀName.,ꢀ2013,ꢀ00,ꢀ1‐3ꢀ|ꢀ1ꢀꢀ
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Forꢀexample,ꢀinꢀtheꢀcontextꢀofꢀtheꢀC‐Hꢀcouplingꢀofꢀaromaticsꢀ withꢀ littleꢀ reductionꢀ inꢀ theꢀ observedꢀ efficiencyꢀ ofꢀ theꢀ cross‐
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DOI: 10.1039/C5CC02676H
andꢀ heteroaromaticsꢀ withꢀ alkenes,ꢀ Bellerꢀ hasꢀ reportedꢀ theꢀ couplingꢀ(2sꢀandꢀ2t)ꢀ(Tableꢀ3).ꢀ
hydroarylationꢀ ofꢀ styrenesꢀ catalysedꢀ byꢀ FeCl3ꢀ toꢀ giveꢀ theꢀ
Tableꢀ2ꢀVariationꢀofꢀalkeneꢀinꢀtheꢀFe(III)‐mediatedꢀC‐Hꢀcouplingꢀ
correspondingꢀbranchedꢀ1,1‐diarylalkanesꢀthatꢀlikelyꢀproceedsꢀ
byꢀanꢀSEArꢀpathway.6ꢀ
FeCl3 (4 equiv.)
MeNO2/CH2Cl2
MeO
SPh
MeO
SPh
Cl
ꢀ
HereinꢀweꢀdescribeꢀaꢀFe(III)‐mediatedꢀC‐Hꢀorthoꢀcouplingꢀofꢀ
R
+
H
rt, air, 2 h
arenesꢀ andꢀ unactivatedꢀ alkenesꢀ directedꢀ byꢀ sulfurꢀ thatꢀ givesꢀ
theꢀ correspondingꢀ linearꢀ β‐chloroarenesꢀ selectivelyꢀ (Schemeꢀ
1B).ꢀ Aꢀ likelyꢀ mechanismꢀ forꢀ theꢀ couplingꢀ ofꢀ theꢀ twoꢀ
nucleophilicꢀ components7ꢀ involvesꢀ theꢀ quenchingꢀ ofꢀ radicalꢀ
cationsꢀ generatedꢀ byꢀ Fe(III)‐mediatedꢀ electron‐transferꢀ
activationꢀ ofꢀ theꢀ areneꢀ partnerꢀ withꢀ simpleꢀ alkenes:ꢀ aꢀ newꢀ
strategyꢀforꢀareneꢀC‐H/alkeneꢀcross‐coupling.8ꢀ
R
1a
2a-j
5 equiv.
OMe
Substrate
OMe
Entry
Product
Yield (%)a
MeO
SPh
Cl
2a
1
64
4
4
OMe
ꢀ
Initialꢀ studiesꢀ focussedꢀ onꢀ theꢀ reactionꢀ ofꢀ arylꢀ sulfideꢀ 1aꢀ
MeO
SPh
Cl
andꢀ 1‐octene,ꢀ usingꢀ inexpensiveꢀ FeCl3ꢀ (Tableꢀ 1).ꢀ Entriesꢀ 1‐4ꢀ
showꢀthatꢀsolventꢀplaysꢀanꢀimportantꢀroleꢀinꢀtheꢀreaction.9ꢀInꢀ
CH2Cl2,ꢀstartingꢀmaterialꢀwasꢀefficientlyꢀconsumedꢀusingꢀFeCl3ꢀ
(2.2ꢀequiv.)ꢀasꢀtheꢀoxidantꢀatꢀroomꢀtemperatureꢀinꢀ1.5ꢀhꢀandꢀ
theꢀcouplingꢀproductꢀ2aꢀwasꢀobtainedꢀinꢀ36%ꢀyieldꢀ(Entryꢀ3).ꢀ
Useꢀ ofꢀ theꢀ oxidantsꢀ FeCl3.6H2O,ꢀ FeBr3,ꢀ Fe(acac)3ꢀ gaveꢀ lowerꢀ
conversionsꢀ andꢀ yieldsꢀ ofꢀ productꢀ (Entriesꢀ 5‐7).ꢀ Theꢀ reactionꢀ
wasꢀ furtherꢀ improvedꢀ byꢀ changingꢀ theꢀ atmosphereꢀ fromꢀ N2:ꢀ
theꢀ reactionꢀ wasꢀ foundꢀ toꢀ beꢀ asꢀ efficientꢀ whenꢀ runꢀ inꢀ airꢀ asꢀ
whenꢀunderꢀanꢀO2ꢀatmosphereꢀ(Entriesꢀ8ꢀandꢀ9).ꢀReducingꢀtheꢀ
amountꢀ ofꢀ alkeneꢀ usedꢀ inꢀ theꢀ couplingꢀ toꢀ 5ꢀ equiv.ꢀ didꢀ notꢀ
affectꢀtheꢀyieldꢀgreatlyꢀ(Entryꢀ10),ꢀhowever,ꢀtheꢀuseꢀofꢀ2ꢀequiv.ꢀ
ofꢀ alkeneꢀ loweredꢀ theꢀ yieldꢀ ofꢀ 2aꢀ significantlyꢀ (Entryꢀ 11).ꢀ
Similarly,ꢀ theꢀ useꢀ ofꢀ lessꢀ FeCl3ꢀ (1ꢀ equiv.)ꢀ alsoꢀ resultedꢀ inꢀ aꢀ
lowerꢀyieldꢀofꢀ2aꢀ(Entryꢀ12).ꢀInꢀallꢀtheꢀreactionsꢀinꢀTableꢀ1,ꢀtheꢀ
onlyꢀ compoundsꢀ observedꢀ inꢀ theꢀ productꢀ mixturesꢀ wereꢀ 2aꢀ
andꢀstartingꢀmaterialꢀ1aꢀandꢀtheꢀpoorꢀmassꢀbalanceꢀinꢀsomeꢀ
reactionsꢀ wasꢀ ascribedꢀ toꢀ decompositionꢀ ofꢀ aꢀ radical‐cationꢀ
intermediateꢀ(videꢀinfra).ꢀToꢀaddressꢀthisꢀissue,ꢀslowꢀadditionꢀ
ofꢀaꢀsolutionꢀofꢀFeCl3ꢀinꢀMeNO2ꢀtoꢀtheꢀsulfideꢀandꢀalkeneꢀwasꢀ
employedꢀ(Tableꢀ1,ꢀentriesꢀ13‐14).ꢀUsingꢀ2.2ꢀequiv.ꢀofꢀFeCl3ꢀinꢀ
theꢀ slowꢀ additionꢀ protocolꢀ gaveꢀ aꢀ greatlyꢀ improvedꢀ massꢀ
balanceꢀ(Entryꢀ13).ꢀFinally,ꢀinꢀtheꢀoptimisedꢀconditions,ꢀtheꢀuseꢀ
ofꢀmoreꢀFeCl3ꢀ(4ꢀequiv.)ꢀandꢀtheꢀslowꢀadditionꢀprotocolꢀgaveꢀaꢀ
70%ꢀ yieldꢀ ofꢀ 2aꢀ withꢀ littleꢀ startingꢀ materialꢀ remainingꢀ (Entryꢀ
14).ꢀWithꢀoptimisedꢀreactionꢀconditionsꢀinꢀhand,ꢀweꢀbeganꢀtoꢀ
assessꢀtheꢀscopeꢀofꢀtheꢀprocessꢀbyꢀvaryingꢀtheꢀterminalꢀalkeneꢀ
cross‐couplingꢀ partnerꢀ (Tableꢀ 2).ꢀ Bromide,ꢀ chloride,ꢀ iodide,ꢀ
nitro,ꢀ alkyl,ꢀ arylꢀ andꢀ alkenylꢀ groupsꢀ wereꢀ toleratedꢀ inꢀ theꢀ
alkeneꢀ partnersꢀ andꢀ productsꢀ wereꢀ obtainedꢀ inꢀ goodꢀ yieldsꢀ
(46‐70%)ꢀ (Entriesꢀ 1‐10).ꢀ Interestinglyꢀ 1,6‐heptadieneꢀ
underwentꢀ selectiveꢀ mono‐couplingꢀ andꢀ noꢀ doubleꢀ additionꢀ
productꢀwasꢀobservedꢀ(videꢀinfra)ꢀ(Entryꢀ3).ꢀTheꢀscopeꢀofꢀtheꢀ
processꢀ withꢀ regardꢀ toꢀ theꢀ arylꢀ sulfideꢀ partnerꢀ wasꢀ nextꢀ
investigatedꢀ (Tableꢀ 3).ꢀ Althoughꢀ theꢀ processꢀ isꢀ currentlyꢀ
sensitiveꢀ toꢀ substitutionꢀ inꢀ theꢀ arylꢀ ringꢀ undergoingꢀ couplingꢀ
(videꢀ infra),ꢀ significantꢀ variationꢀ wasꢀ toleratedꢀ inꢀ theꢀ non‐
reactingꢀarylꢀgroupꢀandꢀmethylꢀ(2k),ꢀbromideꢀ(2l),ꢀfluorideꢀ(2mꢀ
andꢀ2r),ꢀnitroꢀ(2n),ꢀtrifluoromethylꢀ(2o),ꢀandꢀmethoxyꢀ(2pꢀandꢀ
2q)ꢀsubstituents,ꢀinꢀvariousꢀpositionsꢀonꢀtheꢀring,ꢀprovedꢀtoꢀbeꢀ
compatibleꢀwithꢀtheꢀcross‐coupling.ꢀFinally,ꢀtheꢀmethylꢀetherꢀ
groupsꢀ inꢀ 1aꢀ couldꢀ beꢀ changedꢀ toꢀ iso‐propylꢀ andꢀ allylꢀ ethersꢀ
2b
2c
2
3
65
56
2
3
2
3
OMe
OMe
MeO
SPh
Cl
MeO
MeO
SPh
Cl
2d
Br
Br
Br
4
5
60
53
5
3
5
OMe
OMe
SPh
Cl
2e
Br
3
3
MeO
SPh
Cl
2f
Cl
6
46
3
Cl
OMe
MeO
SPh
Cl
2g
I
I
7
8
49
48
3
3
OMe
MeO
SPh
Cl
2h
NO2
5
NO2
5
OMe
MeO
MeO
SPh
Cl
2i
Ph
9
63
6
Ph
6
OMe
OMe
SPh
Cl
2j
10
46b
aꢀIsolatedꢀyields.ꢀbꢀ1:1ꢀMixtureꢀofꢀdiastereoisomers.ꢀ
Theꢀ productsꢀ ofꢀ theꢀ C‐Hꢀ arene/alkeneꢀ cross‐couplingꢀ areꢀ richꢀ inꢀ
syntheticꢀpotentialꢀ(Figureꢀ1).ꢀForꢀexample,ꢀdirectedꢀmetalationꢀandꢀ
electrophilicꢀquenchingꢀ(3a‐c),ꢀsulfurꢀoxidationꢀ(3d),ꢀreductionꢀandꢀ
eliminationꢀ ofꢀ chlorideꢀ (3eꢀ andꢀ 3f),ꢀ andꢀ SN2ꢀ displacementꢀ ofꢀ
2ꢀ|ꢀJ.ꢀName.,ꢀ2012,ꢀ00,ꢀ1‐3ꢀ
Thisꢀjournalꢀisꢀ©ꢀTheꢀRoyalꢀSocietyꢀofꢀChemistryꢀ20xxꢀ
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chlorideꢀ (3g)ꢀ canꢀ beꢀ carriedꢀ out.ꢀ Attractively,ꢀ 3fꢀ isꢀ formallyꢀ theꢀ partnersꢀ haveꢀ higherꢀ oxidationꢀ potentialsꢀ thanꢀ theꢀ arylꢀ sulfides.13ꢀ
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productꢀofꢀanꢀoxidativeꢀHeckꢀreactionꢀinvolvingꢀ1aꢀandꢀ1‐octene.10ꢀ
Notably,ꢀ theꢀ productsꢀ ofꢀ theꢀ cross‐couplingꢀ resembleꢀ biologicallyꢀ
DOI: 10.1039/C5CC02676H
Preliminaryꢀattemptsꢀtoꢀinterceptꢀradicalꢀ6ꢀusingꢀaꢀ5‐hexenylꢀradicalꢀ
cyclisationꢀ wereꢀ unsuccessfulꢀ (Tableꢀ 2,ꢀ entryꢀ 3:ꢀ 2cꢀ wasꢀ theꢀ onlyꢀ
importantꢀ alkylresorcinols.11ꢀ Finally,ꢀ coupledꢀ productsꢀ undergoꢀ
coupledꢀ product)ꢀ suggestingꢀ thatꢀ radicalꢀ oxidationꢀ underꢀ theꢀ
deprotectionꢀtoꢀgiveꢀimportantꢀbenzofuranꢀmotifsꢀ(3h).ꢀ
experimentalꢀconditionsꢀisꢀfast.15ꢀ
Tableꢀ3ꢀVariationꢀofꢀarylꢀsulfideꢀinꢀtheꢀFe(III)‐mediatedꢀC‐Hꢀcouplingꢀ
MeO
R
SPh
Cl
MeO
SO2Ph
Cl
MeO
SC6H4m-OMe
R2
R2
C6H13
C6H13
C6H13
FeCl3 (4 equiv.)
MeNO2/CH2Cl2
R1O
S
OMe
OMe
R1O
S
H
OMe
Cl
+
C6H13
5 equiv.
3a R = D, quant
3b R = I, 95%
3c R = Me, 87%
3d 95%
3e 86% brsm
(from 2p;
rt, air, 2 h
C6H13
(mCPBA, CH2Cl2)
1b-j
2k-s
n-Bu3SnH, AIBN
OR1
OR1
benzene)
(n-BuLi, THF, -78 °C to rt
then MeOD, or I2, or MeI)
Br
F
MeO
SPh
MeO
C5H11
SPh
N3
HO
SPh
C6H13
MeO
S
MeO
S
MeO
S
OMe
OMe
O
Cl
Cl
Cl
C6H13
3f 53 %
3h 53%
3g 88% brsm
C6H13
(NaOEt, EtOH)
C6H13
(NaN3, DMF)
C6H13
(from 2t;
cat. Pd(PPh3)4, MeOH, K2CO3)
OMe
OMe
OMe
Figureꢀ1ꢀSyntheticꢀmanipulationꢀofꢀcoupledꢀproductꢀ2aꢀ
2k 53%
2l 65%
2m 66%
NO2
CF3
Bothꢀtheꢀeaseꢀofꢀoxidationꢀofꢀtheꢀarylꢀsulfideꢀandꢀtheꢀstabilityꢀofꢀtheꢀ
resultantꢀ radicalꢀ cationꢀ 4ꢀ appearꢀ toꢀ beꢀ keyꢀ toꢀ theꢀ successꢀ ofꢀ theꢀ
couplingꢀ process.ꢀ Forꢀ example,ꢀ attemptedꢀ couplingꢀ ofꢀ 3‐
methoxyphenylꢀ phenylsulfideꢀ withꢀ 1‐octeneꢀ ledꢀ toꢀ completeꢀ
consumptionꢀ ofꢀ startingꢀ materialꢀ butꢀ onlyꢀ aꢀ traceꢀ ofꢀ couplingꢀ
product.ꢀ Asꢀ weꢀ haveꢀ determinedꢀ theꢀ oxidationꢀ potentialꢀ ofꢀ 3‐
methoxyphenylꢀphenylsulfideꢀtoꢀbeꢀveryꢀsimilarꢀtoꢀthatꢀofꢀ1aꢀ(+1.72ꢀ
Vꢀ(vsꢀSHE)ꢀinꢀMeCN),12ꢀweꢀbelieveꢀdestructiveꢀsideꢀreactionsꢀofꢀtheꢀ
arylꢀ radicalꢀ cationꢀ derivedꢀ fromꢀ 3‐methoxyphenylꢀ phenylsulfideꢀ
resultsꢀinꢀinefficientꢀcross‐coupling.ꢀThus,ꢀtheꢀstabilityꢀofꢀtheꢀradicalꢀ
cationꢀ4ꢀmayꢀbeꢀtheꢀmostꢀimportantꢀroleꢀofꢀsubstitutionꢀinꢀtheꢀarylꢀ
sulfide.16ꢀ
MeO
MeO
S
MeO
S
MeO
S
Cl
Cl
Cl
C6H13
C6H13
C6H13
OMe
OMe
OMe
2n 75%
MeO
2o 75%
2p 60%
OMe
F
MeO
S
MeO
S
RO
S
Cl
Cl
Cl
C6H13
C6H13
C6H13
OMe
OMe
OR
Cl
Cl
MeO
SPh
MeO
SPh
2q 47%
2r 64%
2s R = i-Pr, 65%
2t R = allyl, 50%
Fe(III)
– 1e
R
1a
H
Theꢀ formationꢀ ofꢀ linearꢀ ratherꢀ thanꢀ branchedꢀ couplingꢀ productsꢀ
suggestsꢀthatꢀanꢀSEArꢀprocessꢀisꢀnotꢀinꢀoperation.6ꢀFurthermore,ꢀtheꢀ
useꢀ ofꢀ non‐redoxꢀ activeꢀ Lewisꢀ acidsꢀ (e.g.ꢀ BF3•OEt2,ꢀ Sc(OTf)3)ꢀ
resultedꢀ inꢀ noꢀ reaction.12ꢀ Aꢀ plausibleꢀ mechanismꢀ forꢀ theꢀ Fe(III)‐
mediatedꢀ C‐Hꢀ arene/alkeneꢀ cross‐couplingꢀ ofꢀ arylꢀ sulfidesꢀ isꢀ
illustratedꢀ inꢀ Schemeꢀ 2.ꢀ Singleꢀ electronꢀ oxidationꢀ byꢀ theꢀ strongꢀ
anhydrousꢀoxidantꢀFeCl3ꢀ(approx.ꢀ+2.00ꢀVꢀ(vsꢀSHE)ꢀinꢀMeCN)9ꢀgivesꢀ
radicalꢀcationꢀ4ꢀthatꢀundergoesꢀcouplingꢀwithꢀtheꢀterminalꢀalkeneꢀ
partnerꢀtoꢀgiveꢀintermediateꢀradicalꢀcationꢀ5ꢀthatꢀisꢀdeprotonatedꢀtoꢀ
giveꢀ radicalꢀ 6.ꢀ Weꢀ haveꢀ determinedꢀ theꢀ oxidationꢀ potentialꢀ ofꢀ 1aꢀ
andꢀfoundꢀitꢀtoꢀbeꢀcompatibleꢀwithꢀtheꢀaboveꢀmechanismꢀ(+1.71ꢀVꢀ
(vsꢀ SHE)ꢀ inꢀ MeCN).12ꢀ Oxidationꢀ ofꢀ 6ꢀ withꢀ FeCl3ꢀ thenꢀ givesꢀ
carbocationꢀ 7ꢀ thatꢀ isꢀ quenchedꢀ byꢀ chlorideꢀ toꢀ giveꢀ couplingꢀ
productsꢀ 2.ꢀ Thisꢀ mechanismꢀ isꢀ indirectlyꢀ supportedꢀ byꢀ theꢀ
observationꢀ thatꢀ theꢀ well‐knownꢀ oxidantꢀ CANꢀ mediatesꢀ theꢀ
transformation:ꢀ couplingꢀ ofꢀ 1aꢀ withꢀ 1‐octeneꢀ gaveꢀ theꢀ nitrateꢀ
analogousꢀ toꢀ 2aꢀ inꢀ 47%ꢀ yield.12,14ꢀ Crucially,ꢀ theꢀ terminalꢀ alkeneꢀ
MeO
OMe
4
5
R
– HCl
MeO
SPh
MeO
SPh
Fe(III)
– 1e
2
MeO
MeO
R
R
7
6
Schemeꢀ2ꢀProposedꢀmechanismꢀofꢀFe(III)‐mediatedꢀC‐Hꢀarene/alkeneꢀcouplingꢀꢀ
Changingꢀ theꢀ electronicꢀ propertiesꢀ ofꢀ theꢀ paraꢀ substituentꢀ inꢀ theꢀ
arylꢀ groupꢀ notꢀ involvedꢀ inꢀ cross‐couplingꢀ hadꢀ anꢀ effectꢀ onꢀ theꢀ
overallꢀ yieldꢀ ofꢀ theꢀ couplingꢀ processꢀ (Tableꢀ 3).ꢀ Somewhatꢀ
surprisingly,ꢀcouplingꢀreactionsꢀtoꢀgiveꢀsulfidesꢀ 2nꢀandꢀ2oꢀbearingꢀ
electron‐withdrawingꢀnitroꢀandꢀtrifluoromethylꢀgroups,ꢀproceededꢀ
inꢀ higherꢀ yieldꢀ comparedꢀ toꢀ theꢀ couplingꢀ ofꢀ analogousꢀ substratesꢀ
lackingꢀtheseꢀsubstituents.ꢀAꢀcompetitionꢀreactionꢀbetweenꢀ1aꢀandꢀ
1nꢀ (limitingꢀ FeCl3)ꢀ ledꢀ toꢀ theꢀ selectiveꢀ formationꢀ ofꢀ 2aꢀ suggestingꢀ
Thisꢀjournalꢀisꢀ©ꢀTheꢀRoyalꢀSocietyꢀofꢀChemistryꢀ20xxꢀ
J.ꢀName.,ꢀ2013,ꢀ00,ꢀ1‐3ꢀ|ꢀ3ꢀ
Pleaseꢀdoꢀnotꢀadjustꢀmarginsꢀ

Pleaseꢀdoꢀnotꢀadjustꢀmarginsꢀ
ChemComm
Page 4 of 4
COMMUNICATIONꢀ
JournalꢀNameꢀ
Zhang,ꢀOrg.ꢀLett.,ꢀ2014,ꢀ16,ꢀ46;ꢀc)ꢀX.ꢀZhang,ꢀQ.ꢀZhu,ꢀY.ꢀZhang,ꢀ
thatꢀ theꢀ rateꢀ ofꢀ couplingꢀ isꢀ highestꢀ forꢀ electron‐richꢀ substratesꢀ
(Schemeꢀ 3).ꢀ Theꢀ higherꢀ yieldsꢀ obtainedꢀ forꢀ theꢀ cross‐couplingꢀ ofꢀ
sulfidesꢀtoꢀgiveꢀ2nꢀandꢀ2oꢀ(Tableꢀ3)ꢀmayꢀthereforeꢀsuggestꢀthatꢀaꢀ
slowerꢀ rateꢀ ofꢀ substrateꢀ oxidationꢀ preventsꢀ theꢀ build‐upꢀ ofꢀ largeꢀ
concentrationsꢀ ofꢀ radicalꢀ cationsꢀ whichꢀ leadsꢀ toꢀ theirꢀ
decomposition.16ꢀ
Y.ꢀLiꢀandꢀZ.ꢀShi,ꢀChem.ꢀEur.ꢀJ.,ꢀ2013,ꢀ19,ꢀ11898V;ꢀiedw)ꢀAMrtic.lꢀeYOun,lꢀinYe.ꢀ
DOI: 10.1039/C5CC02676H
Xie,ꢀC.ꢀXieꢀandꢀY.ꢀZhang,ꢀOrg.ꢀLett.,ꢀ2012,ꢀ14,ꢀ2164.ꢀ
C.ꢀSun,ꢀB.ꢀLiꢀandꢀZ.ꢀShi,ꢀChem.ꢀRev.,ꢀ2011,ꢀ111,ꢀ1293.ꢀ
ꢀJ.ꢀKischel,ꢀI.ꢀJovel,ꢀK.ꢀMertins,ꢀA.ꢀZapfꢀandꢀM.ꢀBeller,ꢀOrg.ꢀLett.ꢀ
2006,ꢀ8,ꢀ19.ꢀ
7Forꢀreviewsꢀonꢀmetal‐mediatedꢀoxidativeꢀcoupling,ꢀsee:ꢀa)ꢀ
C.ꢀ Liu,ꢀ H.ꢀ Zhang,ꢀ W.ꢀ Shiꢀ andꢀ A.ꢀ Li,ꢀ Chem.ꢀ Rev.,ꢀ 2011,ꢀ 111,ꢀ
1780;ꢀb)ꢀC.ꢀLiu,ꢀD.ꢀLiuꢀandꢀA.ꢀLei,ꢀAcc.ꢀChem.ꢀRes.,ꢀ2014,ꢀ47,ꢀ
3459.ꢀ
ꢀForꢀoxidativeꢀradicalꢀcouplingsꢀofꢀsulfides,ꢀsee:ꢀa)ꢀH.ꢀCao,ꢀD.ꢀ
Liu,ꢀC.ꢀLiu,ꢀX.ꢀHuꢀandꢀA.ꢀLei,ꢀOrg.ꢀBiomol.ꢀChem.ꢀ2015,ꢀDOI:ꢀ
10.1039/C4OB02564D;ꢀb)ꢀA.ꢀKamimura,ꢀT.ꢀNokubi,ꢀK.ꢀNasu,ꢀ
Y.ꢀYakechi,ꢀY.ꢀIshihara,ꢀK.ꢀKato,ꢀS.ꢀNoguchi,ꢀM.ꢀWatanabe,ꢀM.ꢀ
Shirai,ꢀM.ꢀSumimotoꢀandꢀH.ꢀUno,ꢀChem.ꢀLett.,ꢀ2012,ꢀ41,ꢀ950.ꢀ
Similarꢀ pathwaysꢀ haveꢀ beenꢀ proposedꢀ forꢀ otherꢀ
transformations.ꢀ See:ꢀ c)ꢀ L.ꢀ Meniniꢀ andꢀ E.ꢀ V.ꢀ Gusevskaya,ꢀ
Chem.ꢀCommun.,ꢀ2006,ꢀ209;ꢀd)ꢀL.ꢀYang,ꢀZ.ꢀLuꢀandꢀS.ꢀS.ꢀStahl,ꢀ
Chem.ꢀ Commun.,ꢀ 2009,ꢀ 6460;ꢀ e)ꢀ X.ꢀ Chen,ꢀ X.ꢀ Hao,ꢀ C.ꢀ E.ꢀ
GoodhueꢀandꢀJ.ꢀYu,ꢀJ.ꢀAm.ꢀChem.ꢀSoc.,ꢀ2006,ꢀ128,ꢀ6790;ꢀf)ꢀZ.ꢀ
Huang,ꢀL.ꢀJin,ꢀY.ꢀFeng,ꢀP.ꢀPeng,ꢀH.ꢀYiꢀandꢀA.ꢀLei,ꢀAngew.ꢀChem.ꢀ
Int.ꢀEd.,ꢀ2013,ꢀ52,ꢀ7151.ꢀ
5
6
7
MeO
SPh
MeO
SPh
Cl
C6H13
(5 equiv.)
8
2a 30 %
(1a 64%)
1a
C6H13
FeCl3 (1 equiv.)
OMe
OMe
OMe
CH2Cl2/MeNO2
air, rt, 2 h
MeO
SC6H4p-NO2
MeO
SC6H4p-NO2
Cl
2n
not observed
(1n 96 %)
C6H13
1n
OMe
Schemeꢀ3ꢀCompetitionꢀexperimentꢀꢀ
Inꢀ summary,ꢀ Fe(III)‐mediatedꢀ C‐Hꢀ orthoꢀ couplingꢀ ofꢀ arenesꢀ andꢀ
unactivatedꢀ terminalꢀ alkenesꢀ directedꢀ byꢀ sulfurꢀ deliversꢀ linearꢀ
productsꢀ ofꢀ alkeneꢀ chloroarylationꢀ inꢀ goodꢀ yieldsꢀ andꢀ withꢀ highꢀ
selectivity.ꢀ Aꢀ novelꢀ mechanismꢀ involvingꢀ redox‐activationꢀ ofꢀ theꢀ
areneꢀpartnerꢀandꢀalkeneꢀadditionꢀtoꢀtheꢀresultantꢀradicalꢀcationsꢀisꢀ
proposed.ꢀ
9
ꢀFormalꢀ potentialꢀ ofꢀ Fe(III)/Fe(II)ꢀ inꢀ anhydrousꢀ solutionꢀ isꢀ
+1.57ꢀ Vꢀ vsꢀ Ag/0.01Mꢀ Ag+.ꢀ K.ꢀ Izutsu,ꢀ Electrochemistryꢀ inꢀ
NonaqueousꢀSolutions,ꢀ2002ꢀWiley‐VCH,ꢀVerlagꢀGmbHꢀ&ꢀCo,ꢀ
KGaA.ꢀ
10 C.ꢀJia,ꢀT.ꢀKitamuraꢀandꢀY.ꢀFujiwara,ꢀAcc.ꢀChem.ꢀRes.ꢀ2001,ꢀ34,ꢀ
633.ꢀ
11 A.ꢀB.ꢀRoss,ꢀA.ꢀKamal‐EldinꢀandꢀP.ꢀAman,ꢀNutritionꢀRev.,ꢀ2004,ꢀ
62,ꢀ81.ꢀ
12 ꢀSeeꢀSupportingꢀInformation.ꢀ
Notesꢀandꢀreferencesꢀ
13 D.ꢀA.ꢀNicewiczꢀandꢀD.ꢀS.ꢀHamilton,ꢀSynlett,ꢀ2014,ꢀ25,ꢀ1191.ꢀ
14 Anꢀ alternativeꢀ processꢀ involvingꢀ electrophilicꢀ metalationꢀ ofꢀ
theꢀarylꢀsulfideꢀfollowedꢀbyꢀcarbometalationꢀofꢀtheꢀalkeneꢀisꢀ
lessꢀ likely.ꢀ Forꢀ nucleophilicꢀ metalation,ꢀ see:ꢀ a)ꢀ J.ꢀ S.ꢀ Bair,ꢀ Y.ꢀ
Schramm,ꢀ A.ꢀ G.ꢀ Sergeev,ꢀ E.ꢀ Clot,ꢀ O.ꢀ Eisensteinꢀ andꢀ J.ꢀ F.ꢀ
Hartwig,ꢀJ.ꢀAm.ꢀChem.ꢀSoc.,ꢀ2014,ꢀ136,ꢀ13098;ꢀb)ꢀY.ꢀHirata,ꢀA.ꢀ
Yada,ꢀ E.ꢀ Morita,ꢀ Y.ꢀ Nakao,ꢀ T.ꢀ Hiyama,ꢀ M.ꢀ Ohashiꢀ andꢀ S.ꢀ
Ogoshi,ꢀJ.ꢀAmꢀ.ꢀChem.ꢀSoc.,ꢀ2010,ꢀ132,ꢀ10070;ꢀc)ꢀY.ꢀNakao,ꢀN.ꢀ
Kashihara,ꢀ K.ꢀ S.ꢀ Kanyivaꢀ andꢀ T.ꢀ Hiyama,ꢀ J.ꢀ Am.ꢀ Chem.ꢀ Soc.,ꢀ
2008,ꢀ130,ꢀ16170.ꢀ
1
ꢀForꢀrecentꢀreviewsꢀsee:ꢀa)ꢀP.ꢀB.ꢀArockiam,ꢀC.ꢀBruneauꢀandꢀP.ꢀ
H.ꢀ Dixneauf,ꢀ Chem.ꢀ Rev.,ꢀ 2012,ꢀ 112,ꢀ 5879;ꢀ b)ꢀ J.ꢀ Wencel‐
Delord,ꢀT.ꢀDröge,ꢀFꢀLiuꢀandꢀF.ꢀGlorius,ꢀChem.ꢀSoc.ꢀRev,ꢀ2011,ꢀ
40,ꢀ4740;ꢀc)ꢀX.ꢀChen,ꢀK.ꢀM.ꢀEngle,ꢀD.ꢀWangꢀandꢀJ.ꢀYu,ꢀAngew.ꢀ
Chem.ꢀInt.ꢀEd.,ꢀ2009,ꢀ48,ꢀ5094.ꢀ
D.ꢀ A.ꢀ Colby,ꢀ R.ꢀ G.ꢀ Bergmanꢀ andꢀ J.ꢀ A.ꢀ Ellman,ꢀ Chem.ꢀ Rev.,ꢀ
2010,ꢀ110,ꢀ624.ꢀ
2
3
Forꢀseminalꢀstudies,ꢀsee:ꢀa)ꢀS.ꢀMurai,ꢀF.ꢀKakiuchi,ꢀS.ꢀSekine,ꢀY.ꢀ
Tanaka,ꢀ A.ꢀ Kamatani,ꢀ M.ꢀ Sonoda,ꢀ N.ꢀ Chatani,ꢀ Natureꢀ 1993,ꢀ
366,ꢀ529.ꢀForꢀselectedꢀexamples:ꢀUsingꢀPd,ꢀsee:ꢀb)ꢀD.ꢀNandi,ꢀ
D.ꢀGhosh,ꢀS.ꢀChen,ꢀB.ꢀKuo,ꢀN.ꢀM.ꢀWangꢀandꢀH.ꢀM.ꢀLee,ꢀJ.ꢀOrg.ꢀ
Chem.,ꢀ2013,ꢀ78,ꢀ3445;ꢀc)ꢀZ.ꢀXu,ꢀB.ꢀXiangꢀandꢀP.ꢀSun,ꢀEur.ꢀJ.ꢀ
Org.ꢀChem.,ꢀ2012,ꢀ3069;ꢀd)ꢀL.ꢀWang,ꢀS.ꢀLiu,ꢀZ.ꢀLiꢀandꢀY.ꢀYu,ꢀ
Org.ꢀLett.,ꢀ2011,ꢀ13,ꢀ6137;ꢀe)ꢀC.ꢀWangꢀandꢀH.ꢀGe,ꢀChem.ꢀEur.ꢀ
J.,ꢀ 2011,ꢀ 17,ꢀ 14371;ꢀ f)ꢀ M.ꢀ Tani,ꢀ S.ꢀ Sakaguchiꢀ andꢀ Y.ꢀ Ishii,ꢀ J.ꢀ
Org.ꢀChem.,ꢀ2004,ꢀ69,ꢀ1221;ꢀg).ꢀC.ꢀJia,ꢀW.ꢀLu,ꢀT.ꢀKitamuraꢀandꢀ
Y.ꢀ Fujiwara,ꢀ Org.ꢀ Lett.,ꢀ 1999,ꢀ 1,ꢀ 2097.ꢀ Usingꢀ Ru,ꢀ see:ꢀ h)ꢀ K.ꢀ
Graczyk,ꢀ W.ꢀ Maꢀ andꢀ L.ꢀ Ackermann,ꢀ Org.ꢀ Lett.,ꢀ 2012,ꢀ 14,ꢀ
4110;ꢀi)ꢀK.ꢀPadalaꢀandꢀM.ꢀJeganmohan,ꢀOrg.ꢀLett.,ꢀ2012,ꢀ14,ꢀ
1134;ꢀj)ꢀB.ꢀLi,ꢀJ.ꢀMa,ꢀN.ꢀWang,ꢀH.ꢀFeng,ꢀS.ꢀXuꢀandꢀB.ꢀWang,ꢀ
Org.ꢀ Lett.,ꢀ 2012,ꢀ 14,ꢀ 736;ꢀ kj)ꢀ L.ꢀ Ackermann,ꢀ L.ꢀ Wang,ꢀ R.ꢀ
Wolframꢀ andꢀ A.ꢀ V.ꢀ Lygin,ꢀ Org.ꢀ Lett.,ꢀ 2012,ꢀ 14,ꢀ 728;ꢀ l)ꢀ K.ꢀ
Padala,ꢀ S.ꢀ Pimparkar,ꢀ P.ꢀ Madasamyꢀ andꢀ M.ꢀ Jeganmohan,ꢀ
Chem.ꢀ Commun.,ꢀ 2012,ꢀ 48,ꢀ 7140;ꢀ m)ꢀ K.ꢀ Padalaꢀ andꢀ M.ꢀ
Jeganmohan,ꢀ Org.ꢀ Lett.,ꢀ 2011,ꢀ 13,ꢀ 6144;ꢀ n)ꢀ T.ꢀ Ueyama,ꢀ S.ꢀ
Mochida,ꢀT.ꢀFukutani,ꢀK.ꢀHirano,ꢀT.ꢀSatohꢀandꢀM.ꢀMiura,ꢀOrg.ꢀ
Lett.,ꢀ 2011,ꢀ 13,ꢀ 706.ꢀ Usingꢀ Rh,ꢀ see:ꢀ o)ꢀ P.ꢀ Becker,ꢀ D.ꢀ L.ꢀ
Priebbenow,ꢀR.ꢀPirwerdjanꢀandꢀC.ꢀBolm,ꢀAngew.ꢀChem.ꢀInt.ꢀ
Ed.,ꢀ2014,ꢀ53,ꢀ269;ꢀp)ꢀT.ꢀIitsuka,ꢀP.ꢀSchaal,ꢀK.ꢀHirano,ꢀT.ꢀSatoh,ꢀ
C.ꢀBolmꢀandꢀM.ꢀMiura,ꢀJ.ꢀOrg.ꢀChem.,ꢀ2013,ꢀ78,ꢀ7216;ꢀq)ꢀS.ꢀ
Rakshit,ꢀC.ꢀGrohmann,ꢀT.ꢀBessetꢀandꢀF.ꢀGlorius,ꢀJ.ꢀAm.ꢀChem.ꢀ
Soc.,ꢀ2011,ꢀ133,ꢀ2350;ꢀr)ꢀS.ꢀMochida,ꢀK.ꢀHirano,ꢀT.ꢀSatohꢀandꢀ
M.ꢀMiura,ꢀJ.ꢀOrg.ꢀChem.,ꢀ2011,ꢀ76,ꢀ3024;ꢀs)ꢀS.ꢀH.ꢀPark,ꢀJ.ꢀY.ꢀ
KimꢀandꢀS.ꢀChang,ꢀOrg.ꢀLett.,ꢀ2011,ꢀ13,ꢀ2372;ꢀt)ꢀT.ꢀK.ꢀHyster,ꢀ
D.ꢀM.ꢀDalton,ꢀT.ꢀRovis,ꢀChem.ꢀSci.,ꢀ2015,ꢀ6,ꢀ254.ꢀ
15 ꢀRateꢀofꢀcyclisationꢀ~1ꢀ×ꢀ105ꢀs‐1.ꢀA.ꢀL.ꢀJ.ꢀBeckwith,ꢀTetrahedron,ꢀ
1981,ꢀ18,ꢀ3073.ꢀ
16 ꢀThisꢀisꢀconsistentꢀwithꢀtheꢀobservationꢀthatꢀtheꢀslowꢀadditionꢀ
ofꢀaꢀsolutionꢀofꢀFeCl3ꢀinꢀMeNO2ꢀtoꢀtheꢀarylꢀsulfideꢀandꢀalkeneꢀ
gaveꢀtheꢀhighestꢀyieldsꢀofꢀcoupledꢀproduct.ꢀ
4
ꢀa)ꢀK.ꢀNobushige,ꢀK.ꢀHirano,ꢀT.ꢀSatohꢀandꢀM.ꢀMiura,ꢀOrg.ꢀLett.,ꢀ
2014,ꢀ 16,ꢀ 1188;ꢀ b)ꢀ B.ꢀ Wang,ꢀ C.ꢀ Shen,ꢀ J.ꢀ Yao,ꢀ H.ꢀ Yinꢀ andꢀ Y.ꢀ
4ꢀ|ꢀJ.ꢀName.,ꢀ2012,ꢀ00,ꢀ1‐3ꢀ
Thisꢀjournalꢀisꢀ©ꢀTheꢀRoyalꢀSocietyꢀofꢀChemistryꢀ20xxꢀ
Pleaseꢀdoꢀnotꢀadjustꢀmarginsꢀ