The influence of the ligand chelate effect on iron-amine-catalysed Kumada cross-coupling

Article abstract of DOI:10.1039/c6dt01823h

The application of a variety of iron complexes with chelating amine ligands as pre-catalysts in the representative cross-coupling of 4-tolylmagnesium bromide with cyclohexyl bromide was investigated. The results from this study indicate the performance of the pre-catalyst is inversely proportional to the strength of the chelate or macrocyclic effect of the amine ligand, as determined by the propensity of the ligand to be displaced from the iron centre by reaction with excess benzyl magnesium chloride. The findings from this study are consistent with a catalytic cycle wherein the chelating amine ligand is not coordinated to the iron centre during turnover.

Full text of DOI:10.1039/c6dt01823h

View Article Online
View Journal
Dalton
Transactions
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: R. Bedford, P.
Brenner, D. Elorriaga, J. Harvey and J. Nunn, Dalton Trans., 2016, DOI: 10.1039/C6DT01823H.
This is an Accepted Manuscript, which has been through the
Royal Society of Chemistry peer review process and has been
accepted for publication.
Accepted Manuscripts are published online shortly after
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. We will replace this Accepted Manuscript with the edited
and formatted Advance Article as soon as it is available.
You can find more information about Accepted Manuscripts in the
Information for Authors.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the Ethical guidelines still
apply. In no event shall the Royal Society of Chemistry be held
responsible for any errors or omissions in this Accepted Manuscript
or any consequences arising from the use of any information it
contains.
www.rsc.org/dalton

Page 1 of 8
Ple aDs ae ꢀl dt oo nꢀ n To rt aꢀ and sj ua sc tt ꢀi mo na sr ginsꢀ
View Article Online
DOI: 10.1039/C6DT01823H
JournalꢀNameꢀ
ꢀ
ARTICLEꢀ
Theꢀinfluenceꢀofꢀtheꢀligandꢀchelateꢀeffectꢀonꢀiron-amine-catalysedꢀ
Kumadaꢀcross-couplingꢀ
Receivedꢀ00thꢀJanuaryꢀ20xx,ꢀ
Acceptedꢀ00thꢀJanuaryꢀ20xxꢀ
a
a
a
b
aꢀ
RobinꢀB.ꢀBedford, *ꢀPeterꢀB.ꢀBrenner, ꢀDavidꢀElorriaga, ꢀJeremy,ꢀN.ꢀHarvey ꢀandꢀJoshuaꢀNunn.
DOI:ꢀ10.1039/x0xx00000xꢀ
Theꢀꢀapplicationꢀofꢀaꢀvarietyꢀofꢀironꢀcomplexesꢀwithꢀchelatingꢀamineꢀligandsꢀasꢀpre-catalystsꢀinꢀtheꢀrepresentativeꢀcross-
couplingꢀofꢀ4-tolylmagnesiumꢀbromideꢀwithꢀcyclohexylꢀbromideꢀwasꢀinvestigated.ꢀTheꢀresultsꢀfromꢀthisꢀstudyꢀindicateꢀtheꢀ
performanceꢀofꢀtheꢀpre-catalystꢀisꢀinverselyꢀproportionalꢀtoꢀtheꢀstrengthꢀofꢀtheꢀchelateꢀorꢀmacrocyclicꢀeffectꢀofꢀtheꢀamineꢀ
ligand,ꢀasꢀdeterminedꢀbyꢀtheꢀpropensityꢀofꢀtheꢀligandꢀtoꢀbeꢀdisplacedꢀfromꢀtheꢀironꢀcentreꢀbyꢀreactionꢀwithꢀexcessꢀbenzylꢀ
magnesiumꢀchloride.ꢀTheꢀfindingsꢀfromꢀthisꢀstudyꢀareꢀconsistentꢀwithꢀaꢀcatalyticꢀcycleꢀwhereinꢀtheꢀchelatingꢀamineꢀligandꢀ
isꢀnotꢀcoordinatedꢀtoꢀtheꢀironꢀcentreꢀduringꢀturnover.ꢀ
www.rsc.org/ꢀ
forꢀ theꢀ cross-coupledꢀ product.ꢀ Forꢀ instanceꢀ Nakamuraꢀ andꢀ
Nakamuraꢀ showedꢀ thatꢀ 1,2-bis(dimethylamino)ethane,ꢀ
TMEDA,ꢀ couldꢀ beꢀ employedꢀ toꢀ goodꢀ effect,ꢀ providingꢀ thatꢀ itꢀ
Introductionꢀ
Whileꢀ thereꢀ isꢀ noꢀ doubtꢀ thatꢀ palladium-catalysedꢀ cross-
couplingꢀ isꢀ anꢀ exceptionallyꢀ powerfulꢀ syntheticꢀ methodologyꢀ
wasꢀusedꢀinꢀstoichiometricꢀorꢀgreaterꢀamountsꢀwithꢀrespectꢀtoꢀ
theꢀ Grignardꢀ substrateꢀ andꢀ thatꢀ theꢀ amine-Grignardꢀ mixtureꢀ
wasꢀ addedꢀ slowlyꢀ toꢀ theꢀ reactionꢀ mixture,ꢀ typicallyꢀ withꢀ aꢀ
1
Schemeꢀ1(a)), ꢀtheꢀbenefitsꢀofꢀtheꢀuseꢀofꢀpalladiumꢀareꢀoffsetꢀ
(
byꢀ itsꢀ highꢀ price,ꢀ relativeꢀ toxicityꢀ andꢀ theꢀ environmentalꢀ
5
6
7
2
impactꢀ ofꢀ itsꢀ extraction. ꢀ Accordinglyꢀ thereꢀ hasꢀ beenꢀ muchꢀ
syringeꢀpump. ꢀWe, ꢀandꢀsubsequentlyꢀCahiez, ꢀdemonstratedꢀ
thatꢀTMEDA,ꢀasꢀwellꢀasꢀotherꢀamineꢀligands,ꢀcouldꢀactuallyꢀbeꢀ
usedꢀ inꢀ catalyticꢀ quantitiesꢀ andꢀ thatꢀ slowꢀ additionꢀ wasꢀ notꢀ
alwaysꢀrequiredꢀforꢀgoodꢀactivity.ꢀ
3
recent ꢀeffortꢀexpendedꢀonꢀdevelopingꢀiron-basedꢀcatalystsꢀforꢀ
4
cross-couplings, ꢀdueꢀtoꢀtheꢀfarꢀlowerꢀcost,ꢀtoxicityꢀandꢀsupplyꢀ
issuesꢀ associatedꢀ withꢀ iron.ꢀ Byꢀ farꢀ theꢀ mostꢀ widelyꢀ studiedꢀ
iron-catalysedꢀcross-couplingꢀreactionꢀisꢀtheꢀKumadaꢀreaction,ꢀ
thatꢀ isꢀ theꢀ couplingꢀ ofꢀ Grignardꢀ reagentsꢀ withꢀ alkylꢀ orꢀ arylꢀ
ꢀ
Clearly,ꢀgivenꢀtheꢀsuccessesꢀenjoyedꢀwithꢀTMEDAꢀandꢀotherꢀ
chelatingꢀamines,ꢀitꢀisꢀimportantꢀtoꢀestablishꢀtheꢀrole(s)ꢀplayedꢀ
byꢀ theꢀ ligandsꢀ inꢀ theꢀ catalyticꢀ cycleꢀ ofꢀ theꢀ iron-catalysedꢀ
Kumadaꢀ reaction.ꢀ Inꢀ theꢀ firstꢀ studyꢀ toꢀ addressꢀ thisꢀ issue,ꢀ
4
halidesꢀandꢀrelatedꢀelectrophilicꢀsubstratesꢀ(Schemeꢀ1(b)). ꢀꢀ
Nagashimaꢀ andꢀ co-workersꢀ investigatedꢀ theꢀ reactionꢀ ofꢀ 3ꢀ
(
a)
8
equivalentsꢀ ofꢀ mesitylMgBrꢀ withꢀ FeCl
Theyꢀshowedꢀthatꢀthisꢀgaveꢀtheꢀbis-mesitylꢀcomplexꢀ
reactsꢀ withꢀ octylꢀ bromideꢀ toꢀ giveꢀ theꢀ cross-coupledꢀ productꢀ
andꢀ theꢀ secondꢀ mesitylꢀ complexꢀ .ꢀ Reactionꢀ ofꢀ ꢀ withꢀ theꢀ
Grignardꢀ reagentꢀ regeneratesꢀ .ꢀ Onꢀ theꢀ basisꢀ ofꢀ theseꢀ
3
ꢀ andꢀ excessꢀ TMEDA. ꢀ
[
Pd-cat]
base)
+
R
X
R'
E
R
R'
(
1,ꢀwhichꢀ
X= halide
E = MgY, ZnY,
SnY , BY ...
pseudohalide...
3
2
2
2
1
(
b)
observations,ꢀtheꢀauthorsꢀproposedꢀtheꢀcatalyticꢀcycleꢀoutlinedꢀ
inꢀSchemeꢀ2.ꢀꢀ
[
Fe-cat]
+
R
X
R' MgX
R
R'
ꢀ
ꢀ
Schemeꢀ1.ꢀ(a)ꢀGeneralisedꢀpalladium-catalysedꢀcross-coupling;ꢀ
R
Br
R Mes
(
b)ꢀtheꢀiron-catalysedꢀKumadaꢀreaction.ꢀ
ꢀ
Whileꢀseveralꢀclassesꢀofꢀcomplexesꢀandꢀligandsꢀhaveꢀbeenꢀ
Me2
N
Me2
N
investigated,ꢀamineꢀcomplexesꢀofꢀironꢀhaveꢀbeenꢀfoundꢀtoꢀbeꢀ
particularlyꢀ usefulꢀ pre-catalystsꢀ inꢀ aꢀ rangeꢀ ofꢀ iron-catalysedꢀ
Kumadaꢀreactions,ꢀoftenꢀgivingꢀhighꢀyieldsꢀandꢀgoodꢀselectivityꢀ
Mes
Mes
Mes
Fe
Fe
N
N
Me
2
Br
Me
2
1
2
MgBr2
MesMgBr
ꢀ
Schemeꢀ2.ꢀNagashima’sꢀproposedꢀcatalyticꢀcycle. ꢀꢀ
8
Thisꢀjournalꢀisꢀ©ꢀTheꢀRoyalꢀSocietyꢀofꢀChemistryꢀ20xxꢀ
J.ꢀName.,ꢀ2013,ꢀ00,ꢀ1-3ꢀ|ꢀ1ꢀꢀ
Pleaseꢀdoꢀnotꢀadjustꢀmarginsꢀ

Ple aDs ae ꢀl dt oo nꢀ n To rt aꢀ and sj ua sc tt ꢀi mo na sr ginsꢀ
Page 2 of 8
ARTICLEꢀ
Byꢀ contrast,ꢀ weꢀ demonstratedꢀ thatꢀ inꢀ theꢀ presenceꢀ ofꢀ
JournalꢀNameꢀ
ꢀ
ResultsꢀandꢀDiscussionꢀ
View Article Online
DOI: 10.1039/C6DT01823H
excessꢀ MesMgBr,ꢀ suchꢀ asꢀ wouldꢀ beꢀ seenꢀ underꢀ catalyticꢀ
conditions,ꢀcomplexꢀ ꢀreactsꢀtoꢀgenerateꢀtheꢀhomolepticꢀ‘ate’ꢀ
complexꢀ
duringꢀcatalysisꢀonlyꢀcomplexꢀ
Furthermore,ꢀcomplexꢀ ꢀreactsꢀfarꢀfasterꢀthanꢀcomplexꢀ
OctBr,ꢀ effectivelyꢀ eliminatingꢀ
ꢀ asꢀ aꢀ feasibleꢀ catalyticꢀ FeCl
intermediateꢀ inꢀ theꢀ primaryꢀ cycle.ꢀ Weꢀ insteadꢀ proposedꢀ theꢀ isolatedꢀ theꢀ complexꢀ
Iron-amineꢀchelateꢀcomplexesꢀ
1
9
1
3
ꢀ(Schemeꢀ3). ꢀIndeedꢀ HꢀNMRꢀstudiesꢀrevealedꢀthatꢀ Theꢀchelatingꢀamineꢀcomplexesꢀselectedꢀforꢀstudyꢀareꢀshownꢀ
ꢀisꢀobservedꢀandꢀnotꢀcomplexꢀ
.ꢀ inꢀ Figureꢀ 1.ꢀ Leighꢀ andꢀ co-workersꢀ showedꢀ thatꢀ theꢀ TMEDAꢀ
ꢀwithꢀ adductsꢀ ꢀ andꢀ 6ꢀ bothꢀ formꢀ inꢀ theꢀ reactionꢀ ofꢀ TMEDAꢀ withꢀ
,ꢀ crystallisingꢀ atꢀ differentꢀ rates. ꢀ Thereforeꢀ whileꢀ weꢀ
,ꢀ inꢀ theꢀ catalyticꢀ studiesꢀ (seeꢀ below)ꢀ
cycleꢀshownꢀinꢀSchemeꢀ4, ꢀbasedꢀonꢀtheꢀobservationsꢀaboveꢀ mixturesꢀ ofꢀ TMEDA:FeCl ꢀ wereꢀ usedꢀ instead.ꢀ Theꢀ previouslyꢀ
3
1
3
1
5
1
1
1
2
6
1
0
2
1
2
andꢀ theꢀ findingꢀ thatꢀ theꢀ sameꢀ amountꢀ ofꢀ cross-coupledꢀ reportedꢀcomplexꢀ7ꢀcontainsꢀtheꢀdiamineꢀligandꢀ(-)-sparteine. ꢀ
productꢀ isꢀ generatedꢀ inꢀ theꢀ absenceꢀ ofꢀ TMEDA,ꢀ butꢀ thatꢀ Theꢀ cage-likeꢀ structureꢀ ofꢀ sparteineꢀ givesꢀ muchꢀ higherꢀ
slightlyꢀ increasedꢀ amountsꢀ ofꢀ side-productsꢀ areꢀ obtained,ꢀ conformationalꢀrigidityꢀcomparedꢀwithꢀTMEDA,ꢀwhichꢀinꢀturnꢀ
suggestingꢀ aꢀ competing,ꢀ non-selectiveꢀ pathway,ꢀ possiblyꢀ shouldꢀ leadꢀ toꢀ higherꢀ chelateꢀ complexꢀ stability.ꢀ Theꢀ
9
ꢀ
involvingꢀ ironꢀ nanoparticles. Inꢀ thisꢀ proposedꢀ pathway,ꢀ theꢀ tetradentateꢀ ligandꢀ inꢀ complexꢀ
amineꢀligandꢀisꢀnotꢀinvolvedꢀinꢀtheꢀprimaryꢀcatalyticꢀcycle,ꢀbutꢀ moreꢀstableꢀironꢀcomplexesꢀthanꢀthoseꢀcontainingꢀTMEDA,ꢀdueꢀ
ratherꢀitꢀinterceptsꢀtheꢀthermallyꢀfragileꢀintermediatesꢀderivedꢀ toꢀtheꢀhigherꢀdenticityꢀofꢀtheꢀligand.ꢀComplexꢀ ꢀwasꢀpreparedꢀ
fromꢀtheꢀreactionꢀofꢀtheꢀintermediateꢀ
ꢀwithꢀtheꢀelectrophilicꢀ byꢀreactionꢀofꢀHMTETAꢀwithꢀFeCl ꢀinꢀTHFꢀatꢀrefluxꢀtemperatureꢀ
couplingꢀ partner,ꢀ generatingꢀ
ꢀ beforeꢀ furtherꢀ decompositionꢀ forꢀ 8ꢀ hours,ꢀ andꢀ theꢀ singleꢀ crystalꢀ X-rayꢀ structureꢀ ofꢀ theꢀ
canꢀ occur.ꢀ Subsequentꢀ reactionꢀ ofꢀ
8,ꢀ HMTETA,ꢀ shouldꢀ alsoꢀ giveꢀ
8
4
2
2
2
ꢀ withꢀ excessꢀ MesMgBrꢀ complexꢀ isꢀ shownꢀ inꢀ Figureꢀ 3.ꢀ Asꢀ canꢀ beꢀ seen,ꢀ theꢀ complexꢀ
regeneratesꢀ
3
ꢀviaꢀtheꢀintermediateꢀ
1
.ꢀ
adoptsꢀaꢀcisꢀcoordinationꢀgeometry,ꢀinꢀcontrastꢀtoꢀtheꢀTMEDAꢀ
complexꢀ5.ꢀ
Fe(0) nanoparticles
unselective
secondary
pathway
Me2
Me2
N
NMe2
Cl
Cl
N
Cl
Cl
octBr
oct mes
Fe
Me N Fe
Fe NMe2
N
N
2
N
Me
2
N
Me2
Fe
Cl
"
FeBr(mes)"
Cl
Me N
2
Cl
Cl
primary
pathway
no tmeda
5
6
7
oct mes
octBr
tmeda
Fe
NMe2
NMe
Cl
Fe
N
N
Cl N
Fe
2
N
Cl
N
Br
Fe
Cl-
Fe
4
3
N
Cl
NMe2
N
Cl
NMe
mesMgBr
N
8
9
10
ꢀ
ꢀ
1
Figureꢀ1.ꢀTheꢀironꢀcomplexesꢀexamined.ꢀ
mesMgBr
Inꢀ orderꢀ toꢀ increaseꢀ complexꢀ stabilityꢀ further,ꢀ theꢀ tetra-
methylcyclamꢀ (TMC)-containingꢀ complexꢀ ꢀ wasꢀ preparedꢀ byꢀ
2
warmingꢀ theꢀ ligandꢀ withꢀ FeCl ꢀ inꢀ acetonitrileꢀ atꢀ 40ꢀ °Cꢀ forꢀ 90ꢀ
-
TMEDA
9
ꢀ
1
0
Schemeꢀ3.ꢀAlternativeꢀcatalyticꢀpathway. ꢀꢀ
minutes.ꢀ Theꢀ macrocyclicꢀ natureꢀ ofꢀ theꢀ TMCꢀ ligandꢀ shouldꢀ
conferꢀhigherꢀstabilityꢀofꢀresultantꢀcomplexesꢀcomparedꢀwithꢀ
theꢀ acyclicꢀ HMTETA.ꢀ Theꢀ crystalꢀ structureꢀ ofꢀ 9ꢀ (Figureꢀ 2)ꢀ
revealedꢀ aꢀ five-coordinateꢀ cationicꢀ complex,ꢀ withꢀ chlorideꢀ
ꢀ
Ultimately,ꢀ theseꢀ modelꢀ studiesꢀ areꢀ limitedꢀ becauseꢀ
mesitylꢀ Grignardꢀ isꢀ aꢀ poor,ꢀ non-representativeꢀ substrateꢀ inꢀ
iron-catalysedꢀ cross-couplings,ꢀ withꢀ lowꢀ yieldsꢀ ofꢀ theꢀ cross-
8
,9 counterꢀ ion,ꢀ inꢀ whichꢀ theꢀ TMCꢀ ligandꢀ occupiesꢀ bothꢀ axialꢀ
coupledꢀ productꢀ furnishedꢀ afterꢀ protractedꢀ reactionꢀ times.
ꢀ
coordinationꢀ sitesꢀ andꢀ twoꢀ ofꢀ theꢀ equatorialꢀ ones,ꢀ withꢀ theꢀ
thirdꢀequatorialꢀpositionꢀoccupiedꢀbyꢀchloride.ꢀ
Finally,ꢀ theꢀ previouslyꢀ reportedꢀ complexꢀ 10ꢀ wasꢀ
Accordingly,ꢀweꢀdecidedꢀtoꢀinvestigateꢀtheꢀeffectꢀofꢀvaryingꢀtheꢀ
amine-donorꢀ ligandsꢀ inꢀ theꢀ presenceꢀ ofꢀ aꢀ smaller,ꢀ farꢀ moreꢀ
representativeꢀ arylꢀ nucleophile.ꢀ Clearly,ꢀ ifꢀ theꢀ mechanismꢀ inꢀ
Schemeꢀ3ꢀisꢀstillꢀoperativeꢀwithꢀlessꢀbulkyꢀGrignardꢀreagents,ꢀ
andꢀtheꢀamineꢀisꢀrequiredꢀtoꢀdissociateꢀfromꢀtheꢀironꢀcentreꢀinꢀ
orderꢀforꢀcatalysisꢀtoꢀproceed,ꢀthenꢀthereꢀshouldꢀbeꢀanꢀinverseꢀ
dependenceꢀ ofꢀ catalyticꢀ activityꢀ onꢀ chelateꢀ complexꢀ stability.ꢀ
Theꢀ resultsꢀ fromꢀ thisꢀ studyꢀ supportꢀ thisꢀ hypothesisꢀ andꢀ areꢀ
presentedꢀbelow.ꢀ
1
3
examined, ꢀwhichꢀcontainsꢀanꢀethylene-bridgedꢀcyclamꢀligandꢀ
Me EBC).ꢀInꢀthisꢀcaseꢀtheꢀbicyclicꢀnatureꢀofꢀtheꢀligandꢀwouldꢀ
beꢀ expectedꢀ toꢀ conferꢀ evenꢀ greaterꢀ macrocylicꢀ stabilisation,ꢀ
(
2
comparedꢀwithꢀtheꢀTMCꢀligand,ꢀgivingꢀbyꢀfarꢀtheꢀmostꢀstableꢀ
complexꢀofꢀtheꢀseries.ꢀꢀ
ꢀ
ꢀ
2
ꢀ|ꢀJ.ꢀName.,ꢀ2012,ꢀ00,ꢀ1-3ꢀ
Thisꢀjournalꢀisꢀ©ꢀTheꢀRoyalꢀSocietyꢀofꢀChemistryꢀ20xxꢀ
Pleaseꢀdoꢀnotꢀadjustꢀmarginsꢀ

Page 3 of 8
Ple aDs ae ꢀl dt oo nꢀ n To rt aꢀ and sj ua sc tt ꢀi mo na sr ginsꢀ
JournalꢀNameꢀ
ꢀARTICLEꢀ
Basedꢀ onꢀ bothꢀ theꢀ relativeꢀ productivitiesꢀVoiewfꢀAtrthiceleꢀOpnrlinee-
DOI: 10.1039/C6DT01823H
catalystsꢀ andꢀ theꢀ appearanceꢀ ofꢀ theꢀ reactionꢀ mixtures,ꢀ itꢀ isꢀ
temptingꢀ toꢀ concludeꢀ thatꢀ theꢀ amineꢀ ligandsꢀ doꢀ indeedꢀ
dissociateꢀ fromꢀ theꢀ ironꢀ centreꢀ priorꢀ toꢀ itsꢀ entryꢀ intoꢀ theꢀ
primaryꢀ catalyticꢀ cycle,ꢀ asꢀ hypothesisedꢀ andꢀ outlinedꢀ inꢀ
Schemeꢀ 3.ꢀ Inꢀ thisꢀ scenario,ꢀ amineꢀ dissociationꢀ wouldꢀ beꢀ
triggeredꢀbyꢀreactionꢀwithꢀexcessꢀGrignardꢀreagent,ꢀthereforeꢀ
weꢀnextꢀfocussedꢀonꢀestablishingꢀtheꢀeaseꢀandꢀextentꢀofꢀligandꢀ
dissociationꢀ fromꢀ theꢀ amineꢀ complexesꢀ inꢀ theꢀ presenceꢀ ofꢀ aꢀ
representativeꢀGrignardꢀreagent.ꢀ
Tableꢀ1.ꢀIron-catalysedꢀKumadaꢀcross-coupling.ꢀ
ꢀ
Figureꢀ2.ꢀX-rayꢀcrystalꢀstructuresꢀofꢀcomplexesꢀ8ꢀandꢀ9.ꢀThermalꢀellipsoidsꢀsetꢀatꢀ50%ꢀ
probability;ꢀhydrogenꢀatoms,ꢀchlorideꢀcounter-ionꢀofꢀ9ꢀandꢀthreeꢀmoleculesꢀofꢀMeCNꢀ
solvateꢀinꢀ9ꢀomittedꢀforꢀclarity.ꢀ
MgBr
+
Br
[
Fe-cat] 5mol%
Conditions
Catalyticꢀstudiesꢀ
A: THF, 0 oC, slow addition
11
B: Et O, 40 oC
2
Theꢀcomplexesꢀ
7
ꢀ–ꢀ10,ꢀasꢀwellꢀasꢀtheꢀspeciesꢀformedꢀinꢀsituꢀ
ꢀ
fromꢀFeCl ꢀandꢀTMEDAꢀinꢀTHFꢀwereꢀtestedꢀasꢀpre-catalystsꢀinꢀ
2
a
Entryꢀ
[Fe-cat]ꢀ
Conditions ꢀ
Conversionꢀ
Appearanceꢀatꢀ
endꢀofꢀreactionꢀ
heterogeneousꢀ
theꢀ representativeꢀ cross-couplingꢀ ofꢀ 4-tolylꢀ magnesiumꢀ
bromideꢀ withꢀ cyclohexylbromide,ꢀ underꢀ twoꢀ setsꢀ ofꢀ
b
toꢀ11,ꢀ% ꢀ
1
ꢀ
FeCl
2
ꢀ+ꢀ
Aꢀ
Bꢀ
93ꢀ
conditions.ꢀInꢀtheꢀfirstꢀsetꢀofꢀ(A),ꢀtheꢀreactionꢀwasꢀperformedꢀ
excessꢀ
cꢀ
atꢀ 0ꢀ °Cꢀ withꢀ slowꢀ additionꢀ ofꢀ theꢀ Grignardꢀ reagentꢀ usingꢀ aꢀ
syringeꢀ pump,ꢀ conditionsꢀ similarꢀ toꢀ thoseꢀ reportedꢀ byꢀ
TMEDA
2ꢀ
3ꢀ
FeCl ꢀ+ꢀ2ꢀ
2
77ꢀ
heterogeneousꢀ
5
Nakamura. ꢀMeanwhileꢀinꢀtheꢀsecondꢀsetꢀofꢀconditionsꢀ(
dꢀ
B
)ꢀtheꢀ
TMEDA
7ꢀ
Grignardꢀ reagentꢀ wasꢀ addedꢀ rapidlyꢀ andꢀ theꢀ reactionꢀ wasꢀ
warmedꢀtoꢀ40ꢀ°C,ꢀtoꢀmirrorꢀtheꢀconditionsꢀthatꢀweꢀpreviouslyꢀ
6
exploited. ꢀ Theꢀ resultsꢀ fromꢀ thisꢀ studyꢀ areꢀ summarisedꢀ inꢀ
Aꢀ
Bꢀ
Aꢀ
Bꢀ
Aꢀ
Bꢀ
Aꢀ
Bꢀ
51ꢀ
54ꢀ
19ꢀ
53ꢀ
15ꢀ
3ꢀ
heterogeneousꢀ
heterogeneousꢀ
heterogeneousꢀ
heterogeneousꢀ
homogeneousꢀ
homogeneousꢀ
homogeneousꢀ
homogeneousꢀ
4
ꢀ
7ꢀ
5ꢀ
8ꢀ
6
7
8
9
ꢀ
ꢀ
ꢀ
ꢀ
8ꢀ
Tableꢀ1.ꢀ
9ꢀ
Comparedꢀ withꢀ theꢀ excellentꢀ andꢀ goodꢀ conversionsꢀ
observedꢀ afterꢀ 1ꢀ hourꢀ withꢀ theꢀ TMEDA-containingꢀ systemꢀ
underꢀ slowꢀ andꢀ rapidꢀ additionꢀ ofꢀ theꢀ Grignardꢀ reagentꢀ
respectivelyꢀ (entriesꢀ 1ꢀ andꢀ 2)ꢀ itꢀ isꢀ clearꢀ thatꢀ muchꢀ lowerꢀ
9ꢀ
10ꢀ
10ꢀ
1ꢀ
1
0ꢀ
3ꢀ
a.ꢀ Conditions,ꢀ A:ꢀ CyBrꢀ (1.0ꢀ mmol),ꢀ 4-tolylMgBrꢀ (drop-wise,ꢀ 1.2ꢀ mmol),ꢀ [Fe-cat]ꢀ
activityꢀ isꢀ seenꢀ withꢀ theꢀ pre-catalystꢀ
moreꢀconformationallyꢀrigidꢀdiamineꢀligandꢀsparteineꢀ(entriesꢀ
ꢀ andꢀ 4).ꢀ Evenꢀ worseꢀ activityꢀ isꢀ observedꢀ withꢀ complexꢀ ,ꢀ
7,ꢀ whichꢀ containsꢀ theꢀ
(
(
0.05ꢀmmol),ꢀTHF,ꢀ0ꢀ°C,ꢀ1ꢀh;ꢀB:ꢀCyBrꢀ(1.0ꢀmmol),ꢀ4-tolylMgBrꢀ(2.0ꢀmmol),ꢀ[Fe-cat]ꢀ
1
0.05ꢀ mmol),ꢀ Et2O,ꢀ 40ꢀ °C,ꢀ 1ꢀ h.ꢀ b.ꢀ Conversionꢀ toꢀ 11ꢀ determinedꢀ byꢀ Hꢀ NMRꢀ
spectroscopyꢀ (1,3,5-trimethoxybenzeneꢀ internalꢀ standard).ꢀ c.ꢀ 2.0ꢀ mmol.ꢀ d.ꢀ 0.1ꢀ
3
8
whichꢀ containsꢀ theꢀ tetradentateꢀ chelatingꢀ ligandꢀ HMTETA,ꢀ mmol.ꢀ
underꢀ slowꢀ additionꢀ conditionsꢀ (entryꢀ 5).ꢀ Interestinglyꢀ someꢀ
ReactionsꢀwithꢀbenzylꢀGrignardꢀreagentꢀ
Weꢀ previouslyꢀ foundꢀ thatꢀ theꢀ reactionꢀ ofꢀ eitherꢀ FeCl2ꢀ orꢀ
FeCl /TMEDAꢀwithꢀexcessꢀ4-tolylꢀGrignardꢀatꢀlowꢀtemperatureꢀ
-30ꢀ °C)ꢀ givesꢀ speciesꢀ tentativelyꢀ assignedꢀ asꢀ theꢀ homolepticꢀ
activityꢀ isꢀ recoveredꢀ whenꢀ theꢀ reactionꢀ wasꢀ repeatedꢀ withꢀ
rapidꢀadditionꢀofꢀtheꢀGrignardꢀreagent.ꢀ
Inꢀallꢀtheꢀexamplesꢀabove,ꢀtheꢀcatalysisꢀisꢀaccompaniedꢀbyꢀ
theꢀformationꢀofꢀblack,ꢀheterogeneousꢀreactionꢀmixtures,ꢀmostꢀ
likelyꢀdueꢀtoꢀtheꢀformationꢀofꢀironꢀnanoparticles,ꢀwhichꢀhaveꢀ
previouslyꢀbeenꢀdemonstratedꢀtoꢀbeꢀcatalyticallyꢀcompetentꢀinꢀ
2
(
-
2-ꢀ
3 4
arylferratesꢀ[FeAr ] ꢀandꢀ[FeAr ] respectively,ꢀasꢀcharacterisedꢀ
1
byꢀ HꢀNMRꢀspectroscopy.ꢀInꢀtheꢀlatterꢀcaseꢀtheꢀTMEDAꢀligandꢀ
isꢀ notꢀ coordinatedꢀ toꢀ theꢀ paramagneticꢀ ironꢀ centre,ꢀ butꢀ
insteadꢀmostꢀlikelyꢀcoordinatesꢀtoꢀtheꢀmagnesiumꢀsaltꢀcounter-
ion.ꢀ Whilstꢀ theseꢀ speciesꢀ haveꢀ soꢀ farꢀ provenꢀ tooꢀ thermallyꢀ
fragileꢀforꢀusꢀtoꢀisolate,ꢀweꢀfoundꢀthatꢀweꢀwereꢀableꢀtoꢀisolateꢀ
1
4
15
Kumada ꢀandꢀrelatedꢀcross-couplingꢀreactions. ꢀByꢀcontrast,ꢀ
theꢀ reactionsꢀ catalysedꢀ byꢀ complexesꢀ 9ꢀ orꢀ 10ꢀ remainedꢀ
homogeneousꢀoverꢀtheꢀcourseꢀofꢀtheꢀreactionsꢀunderꢀbothꢀsetsꢀ
ofꢀ conditions,ꢀ andꢀ inꢀ allꢀ casesꢀ gaveꢀ veryꢀ littleꢀ ofꢀ theꢀ cross-
coupledꢀproductꢀ11.ꢀItꢀisꢀclearꢀthatꢀanꢀincreaseꢀinꢀtheꢀchelateꢀ
orꢀmacrocyclicꢀcomplexꢀstabilityꢀleadsꢀtoꢀaꢀsharpꢀdecreaseꢀinꢀ
catalystꢀ performance.ꢀ Thisꢀ isꢀ despiteꢀ theꢀ factꢀ that,ꢀ inꢀ allꢀ theꢀ
casesꢀ examined,ꢀ theꢀ pre-catalystsꢀ shouldꢀ beꢀ capableꢀ ofꢀ
providingꢀ theꢀ cis-disposedꢀ reactiveꢀ sitesꢀ thatꢀ mightꢀ beꢀ
envisagedꢀ asꢀ necessaryꢀ forꢀ catalyticꢀ activityꢀ ifꢀ anꢀ iron-amine-
basedꢀcycleꢀsuchꢀasꢀthatꢀshownꢀinꢀSchemeꢀ2ꢀwereꢀoperative.ꢀꢀ
andꢀ characteriseꢀ theꢀ comparableꢀ Fe(II)ꢀ benzyl-containingꢀ
-
] ꢀ (12),ꢀ asꢀ wellꢀ asꢀ theꢀ Fe(III)ꢀ
anionicꢀ ‘ate’ꢀ complex,ꢀ [FeBn
-
3
4
analogueꢀ[FeBn ] ꢀ(13),ꢀandꢀprobeꢀitsꢀsignificanceꢀasꢀaꢀpossibleꢀ
9
activeꢀintermediateꢀinꢀcross-coupling. ꢀInꢀviewꢀofꢀtheꢀimprovedꢀ
stabilityꢀ ofꢀ iron-benzylꢀ adductsꢀ comparedꢀ toꢀ iron-4-tolylꢀ
intermediates,ꢀweꢀdecidedꢀtoꢀexploreꢀtheꢀreactivityꢀofꢀtheꢀironꢀ
amine-complexesꢀlistedꢀaboveꢀwithꢀbenzylꢀGrignard.ꢀꢀ
ꢀ
ꢀ
Thisꢀjournalꢀisꢀ©ꢀTheꢀRoyalꢀSocietyꢀofꢀChemistryꢀ20xxꢀ
J.ꢀName.,ꢀ2013,ꢀ00,ꢀ1-3ꢀ|ꢀ3ꢀ
Pleaseꢀdoꢀnotꢀadjustꢀmarginsꢀ

Ple aDs ae ꢀl dt oo nꢀ n To rt aꢀ and sj ua sc tt ꢀi mo na sr ginsꢀ
Page 4 of 8
ARTICLEꢀ
JournalꢀNameꢀ
ꢀ
View Article Online
DOI: 10.1039/C6DT01823H
1
Figureꢀ3ꢀshowsꢀtheꢀ HꢀNMRꢀspectraꢀrecordedꢀonꢀadditionꢀofꢀ
varyingꢀamountsꢀofꢀBnMgClꢀtoꢀcomplexꢀ ꢀinꢀTHF.ꢀComplexꢀ ꢀisꢀ
6
6
NMRꢀsilent,ꢀbutꢀtheꢀadditionꢀofꢀoneꢀequivalentꢀofꢀtheꢀGrignardꢀ
reagentꢀ givesꢀ aꢀ spectrumꢀ assignedꢀ asꢀ thatꢀ ofꢀ theꢀ complexꢀ
[
FeClBn(TMEDA)],ꢀ15,ꢀwhichꢀcouldꢀbeꢀisolatedꢀinꢀmodestꢀyieldꢀ
whenꢀtheꢀreactionꢀwasꢀrepeatedꢀonꢀaꢀlargerꢀscale.ꢀAdditionꢀofꢀ
aꢀ furtherꢀ 0.5ꢀ orꢀ 1ꢀ equivalentꢀ ofꢀ theꢀ Grignardꢀ reagentꢀ toꢀ theꢀ
NMR-scaleꢀ reactionꢀ mixtureꢀ ledꢀ toꢀ increasingꢀ amountsꢀ ofꢀ aꢀ
speciesꢀpreviouslyꢀidentifiedꢀbyꢀSenꢀandꢀco-workersꢀasꢀtheꢀbis-
1
6
9
benzylꢀcomplexꢀ14a. ꢀAsꢀdescribedꢀpreviously, ꢀtheꢀadditionꢀofꢀ
excessꢀ BnMgClꢀ rapidlyꢀ ledꢀ toꢀ theꢀ formationꢀ ofꢀ theꢀ ‘ate’ꢀ
ꢀ
ꢀ
1
complexꢀ12.ꢀ
Figureꢀ4.ꢀꢀ(a)ꢀ HꢀNMRꢀspectrumꢀofꢀcomplexꢀ14bꢀinꢀTHF.ꢀ(b)ꢀ14bꢀ+ꢀ20ꢀBnMgCl,ꢀafterꢀ10ꢀ
min.ꢀ(c)ꢀAsꢀabove,ꢀafterꢀ5ꢀh;ꢀpeaksꢀmarkedꢀwithꢀ‘*’ꢀcorrespondꢀtoꢀ‘ate’ꢀcomplexꢀ12.ꢀ
1
Theꢀ HꢀNMRꢀspectrumꢀofꢀtheꢀHMTETA-containingꢀcomplexꢀ
8
ꢀinꢀTHFꢀatꢀroomꢀtemperatureꢀisꢀshownꢀinꢀFigureꢀ5(a),ꢀwhilstꢀ
b)ꢀ showsꢀ theꢀ spectrumꢀ afterꢀ additionꢀ ofꢀ 2ꢀ equivalentsꢀ ofꢀ
(
BnMgCl.ꢀTheꢀlatterꢀspectrumꢀisꢀmoreꢀcomplicatedꢀandꢀisꢀlikelyꢀ
toꢀ correspondꢀ toꢀ theꢀ formationꢀ ofꢀ oneꢀ orꢀ moreꢀ iron-
benzyl/HMTETAꢀ adducts.ꢀ Onꢀ additionꢀ ofꢀ aꢀ furtherꢀ twoꢀ
equivalentsꢀofꢀtheꢀGrignardꢀreagent,ꢀtheꢀtetraamineꢀligandꢀwasꢀ
lostꢀfromꢀtheꢀironꢀcentreꢀandꢀtheꢀ‘ate’ꢀcomplexꢀ12ꢀwasꢀonceꢀ
againꢀtheꢀonlyꢀparamagneticꢀiron-containingꢀcomplexꢀobservedꢀ
(
spectrumꢀ (c)).ꢀ Theꢀ dataꢀ clearlyꢀ showꢀ that,ꢀ asꢀ withꢀ bothꢀ theꢀ
ꢀ
TMEDA-ꢀandꢀsparteine-containingꢀcomplexes,ꢀtheꢀpresenceꢀofꢀ
excessꢀ Grignardꢀ reagentꢀ favoursꢀ theꢀ dissociationꢀ ofꢀ HMTETAꢀ
andꢀ theꢀ concomitantꢀ formationꢀ ofꢀ theꢀ amine-ligand-freeꢀ
1
Figureꢀ3.ꢀ(a)ꢀ HꢀNMRꢀspectrumꢀofꢀcomplexꢀ6ꢀinꢀTHFꢀ(NMRꢀsilent).ꢀ(b)ꢀPartꢀofꢀspectrumꢀ
ofꢀ complexꢀ 15,ꢀ formedꢀ inꢀ situꢀ fromꢀ 6ꢀ andꢀ 1ꢀ equiv.ꢀ BnMgCl/Feꢀ (peakꢀ atꢀ 1067ꢀ ppmꢀ
omitted).ꢀ(c)ꢀandꢀ(d)ꢀadditionꢀofꢀaꢀfurtherꢀ0.5ꢀandꢀ1ꢀequivalentꢀofꢀBnMgCl/Fe.ꢀPeaksꢀ
markedꢀ‘*’ꢀcorrespondꢀtoꢀ[FeBn
2
(TMEDA)],ꢀ(14a).ꢀꢀ
homolepticꢀ‘ate’ꢀcomplexꢀ12.ꢀ
1
Theꢀ Hꢀ spectraꢀ ofꢀ macrocyclicꢀ complexesꢀ
9
ꢀ andꢀ 10ꢀ areꢀ
shownꢀinꢀFigureꢀ6ꢀ(spectraꢀ(a)ꢀandꢀ(c)ꢀrespectively),ꢀmeanwhileꢀ
theꢀspectraꢀofꢀtheꢀredꢀandꢀorangeꢀreactionꢀmixturesꢀrecordedꢀ
1
0ꢀminutesꢀafterꢀadditionꢀofꢀexcessꢀBnMgClꢀ(10ꢀequivalents)ꢀtoꢀ
N
N
N
N
Fe
9ꢀandꢀ10ꢀareꢀshownꢀinꢀplotsꢀ(b)ꢀandꢀ(d)ꢀrespectively.ꢀItꢀisꢀclearꢀ
thatꢀnewꢀparamagneticꢀcomplexesꢀwereꢀformedꢀinꢀbothꢀcases,ꢀ
againꢀpresumablyꢀcontainingꢀbenzylꢀligandsꢀinꢀadditionꢀtoꢀtheꢀ
macrocyclicꢀamineꢀligands.ꢀHowever,ꢀinꢀstarkꢀcontrastꢀtoꢀallꢀofꢀ
theꢀreactionsꢀdiscussedꢀaboveꢀwithꢀironꢀcomplexesꢀofꢀTMEDA,ꢀ
sparteineꢀorꢀHMTETA,ꢀnoneꢀofꢀtheꢀhomolepticꢀanionicꢀcomplexꢀ
2ꢀ 12ꢀwasꢀobservedꢀsuggestingꢀthatꢀtheꢀmacrocyclicꢀligandsꢀwereꢀ
notꢀ displacedꢀ byꢀ theꢀ Grignardꢀ reagent.ꢀ Indeed,ꢀ noꢀ 12ꢀ wasꢀ
Fe
Bn Bn
Bn Bn
1
4a
1
4b
ꢀ
Asꢀ yet,ꢀ noꢀ structuralꢀ evidenceꢀ hasꢀ beenꢀ providedꢀ forꢀ 14a,ꢀ
howeverꢀ Chirikꢀ andꢀ co-workersꢀ haveꢀ reportedꢀ theꢀ crystalꢀ
1
structureꢀ ofꢀ theꢀ equivalentꢀ sparteine-basedꢀ analogue,ꢀ 14b
1
Theꢀ HꢀNMRꢀspectrumꢀofꢀ14b,ꢀformedꢀinꢀsituꢀfromꢀ7ꢀandꢀtwoꢀ
.
observedꢀwhenꢀtheꢀspectraꢀwereꢀrunꢀagainꢀafterꢀ24ꢀhours.ꢀ
ꢀ
equivalentsꢀ ofꢀ benzylꢀ Grignard,ꢀ isꢀ shownꢀ inꢀ Figureꢀ 4(a).ꢀ
Additionꢀofꢀexcessꢀ(20ꢀequivalents)ꢀofꢀGrignardꢀagainꢀledꢀtoꢀtheꢀ
formationꢀ ofꢀ theꢀ anionicꢀ complexꢀ 12,ꢀ butꢀ theꢀ reactionꢀ isꢀ
significantlyꢀ slowerꢀ thanꢀ withꢀ theꢀ Fe-TMEDAꢀ mixture,ꢀ
presumablyꢀ asꢀ aꢀ functionꢀ ofꢀ increasedꢀ chelateꢀ complexꢀ
stabilityꢀwithꢀtheꢀmoreꢀconformationallyꢀconstrainedꢀsparteineꢀ
ligand.ꢀꢀ
(c)ꢀ
(
(
b)ꢀ
a)ꢀ
ꢀ
1
Figureꢀ5.ꢀ(a)ꢀ HꢀNMRꢀspectrumꢀofꢀcomplexꢀ8.ꢀ(b)ꢀandꢀ(c)ꢀSpectraꢀrecordedꢀafterꢀadditionꢀ
ofꢀ2ꢀandꢀ4ꢀequiv.ꢀBnMgClꢀrespectively.ꢀꢀ
4
ꢀ|ꢀJ.ꢀName.,ꢀ2012,ꢀ00,ꢀ1-3ꢀ
Thisꢀjournalꢀisꢀ©ꢀTheꢀRoyalꢀSocietyꢀofꢀChemistryꢀ20xxꢀ
Pleaseꢀdoꢀnotꢀadjustꢀmarginsꢀ

Page 5 of 8
Ple aDs ae ꢀl dt oo nꢀ n To rt aꢀ and sj ua sc tt ꢀi mo na sr ginsꢀ
JournalꢀNameꢀ
ꢀARTICLEꢀ
ꢀ
Half-heightꢀ peakꢀ widthsꢀ forꢀ paramagneticꢀ comVipewoAurnticdlesOꢀ nalirnee ꢀ
DOI: 10.1039/C6DT01823H
reportedꢀ inꢀ Hzꢀ inꢀ parenthesesꢀ afterꢀ theꢀ chemicalꢀ shift.ꢀ
(
(
(
(
d)ꢀ
c)ꢀ
b)ꢀ
a)ꢀ
Elementalꢀ analysesꢀ wereꢀ obtainedꢀ fromꢀ theꢀ microanalyticalꢀ
serviceꢀ atꢀ theꢀ Universityꢀ ofꢀ Bristol.ꢀ Infraredꢀ spectraꢀ wereꢀ
recordedꢀonꢀaꢀPerkinElmerꢀSpectrumꢀ100ꢀFTIRꢀSpectrometer,ꢀ
selectedꢀfrequenciesꢀareꢀreported.ꢀꢀ
ꢀ
2
Preparationꢀofꢀ[{FeCl(μ-Cl)(TMEDA)} ꢀ6.ꢀPreparedꢀfollowingꢀaꢀ
],
ꢀ(4.10ꢀg,ꢀ32.3ꢀmmol)ꢀandꢀTMEDAꢀ
4.90ꢀml,ꢀ32.7ꢀmmol)ꢀwereꢀheatedꢀforꢀ1ꢀhꢀinꢀTHFꢀ(150ꢀml)ꢀatꢀ
1
1
literatureꢀprocedure. ꢀFeCl
2
(
refluxꢀtemperature.ꢀAfterꢀcooling,ꢀtheꢀvolumeꢀwasꢀreducedꢀbyꢀ
aꢀ thirdꢀ andꢀ theꢀ mixtureꢀ cooledꢀ toꢀ –20ꢀ °Cꢀ toꢀ giveꢀ aꢀ cropꢀ ofꢀ
crystalsꢀofꢀ6ꢀ(3.72ꢀg,ꢀ47.4%).ꢀAnal.ꢀFound:ꢀC,ꢀ30.10;ꢀH,ꢀ6.92;ꢀN,ꢀ
ꢀ
11.20.ꢀCalcdꢀforꢀC H Cl Fe N :ꢀC,ꢀ29.66;ꢀH,ꢀ6.64;ꢀN,ꢀ11.53.ꢀ
1
2
32
4
2 4
1
Figureꢀ6.ꢀ(a)ꢀandꢀ(c)ꢀ HꢀNMRꢀspectraꢀofꢀcomplexesꢀ9ꢀandꢀ10ꢀrespectivelyꢀ(THF,ꢀr.t.);ꢀ(b)ꢀ
andꢀ(d)ꢀSpectraꢀrecordedꢀ10ꢀminutesꢀafterꢀadditionꢀofꢀ10ꢀequiv.ꢀBnMgClꢀtoꢀ9ꢀandꢀ10ꢀ
respectively.ꢀꢀ
ꢀ
2
Preparationꢀ ofꢀ [FeCl ((–)-sparteine)],ꢀ 7.ꢀ Aꢀ literatureꢀ
1
2
2
preparationꢀwasꢀfollowed. ꢀToꢀaꢀmixtureꢀofꢀFeCl ꢀ(1.09ꢀg,ꢀ8.60ꢀ
mmol)ꢀinꢀTHFꢀ(5ꢀml)ꢀwasꢀaddedꢀaꢀsolutionꢀofꢀ(-)-sparteineꢀ(2.02ꢀ
g,ꢀ8.60ꢀmmol)ꢀinꢀTHFꢀ(2ꢀml)ꢀandꢀtheꢀreactionꢀmixtureꢀstirredꢀforꢀ
Conclusionsꢀ
1
8ꢀ hꢀ toꢀ giveꢀ aꢀ suspension.ꢀ Theꢀ whiteꢀ solidꢀ wasꢀ isolatedꢀ byꢀ
Theꢀlabilityꢀofꢀtheꢀamineꢀligandsꢀofꢀtheꢀcomplexesꢀ5ꢀ–ꢀ10ꢀinꢀtheꢀ
filtration,ꢀwashedꢀwithꢀdiethylꢀetherꢀandꢀdriedꢀunderꢀreducedꢀ
1
presenceꢀ ofꢀ excessꢀ benzylꢀ Grignardꢀ reflectsꢀ decreasingꢀ
catalyticꢀactivityꢀinꢀtheꢀcouplingꢀofꢀcyclohexylbromideꢀwithꢀ4-
tolylmagnesiumꢀ bromide,ꢀ withꢀ theꢀ leastꢀ labileꢀ systemsꢀ
showingꢀ theꢀ poorestꢀ catalyticꢀ activity.ꢀ Ofꢀ particularꢀ note,ꢀ
pressureꢀtoꢀyieldꢀ
dataꢀ (CDCl )ꢀ wereꢀ inꢀ agreementꢀ withꢀ reportedꢀ values. ꢀ Hꢀ
NMRꢀ (400ꢀ MHz,ꢀ 25.0ꢀ °C,ꢀ THF)ꢀ δꢀ 352.3ꢀ (271,ꢀ 1H),ꢀ 313.5ꢀ (296,ꢀ
H),ꢀ297.1ꢀ(275,ꢀ1H),ꢀ175.9ꢀ(167,ꢀ1H),ꢀ139.2ꢀ(632,ꢀ2H),ꢀ118.3ꢀ
821,ꢀ1H),ꢀ43.3ꢀ(79,ꢀ1H),ꢀ41.8ꢀ(74,ꢀ1H),ꢀ37.5ꢀ(56,ꢀ1H),ꢀ24.5ꢀ(106,ꢀ
H),ꢀ22.9ꢀ(94,ꢀ1H),ꢀ10.9ꢀ(65,ꢀ1H),ꢀ7.2ꢀ(30,ꢀ1H),ꢀ-6.6ꢀ(42,ꢀ1H),ꢀ-7.2ꢀ
53,ꢀ1H),ꢀ-15.1ꢀ(83,ꢀ1H),ꢀ-15.6ꢀ(59,ꢀ1H),ꢀ-22.0ꢀ(68,ꢀ2H),ꢀ-34.3ꢀ(69,ꢀ
H),ꢀ -38.0ꢀ (766,ꢀ 1H),ꢀ -44.6ꢀ (81,ꢀ 1H),ꢀ -69.6ꢀ (797,ꢀ 1H),ꢀ -134.4ꢀ
970,ꢀ 1H).ꢀ Anal.ꢀ Found:ꢀ C,ꢀ 49.62;ꢀ H,ꢀ 6.91;ꢀ N,ꢀ 7.73.ꢀ Calcdꢀ forꢀ
7ꢀ(2.61ꢀg,ꢀ83.9ꢀ%).ꢀTheꢀ HꢀNMRꢀspectroscopicꢀ
1
2 1
3
1
whilstꢀtheꢀcomplexesꢀ9ꢀandꢀ10ꢀdoꢀreactꢀwithꢀbenzylꢀGrignard,ꢀ
(
theꢀamineꢀligandsꢀareꢀnotꢀdisplacedꢀbyꢀexcessꢀGrignard,ꢀunlikeꢀ
theꢀamineꢀligandsꢀinꢀtheꢀotherꢀcomplexesꢀexamined.ꢀTheseꢀtwoꢀ
complexesꢀ showꢀ onlyꢀ veryꢀ poorꢀ activityꢀ asꢀ catalystsꢀ inꢀ theꢀ
cross-couplingꢀ reactionsꢀ andꢀ itꢀ isꢀ importantꢀ toꢀ noteꢀ thatꢀ inꢀ
theseꢀ casesꢀ theꢀ reactionꢀ mixturesꢀ stayꢀ homogeneousꢀ
throughoutꢀ theꢀ catalysis.ꢀ Converselyꢀ TMEDA,ꢀ sparteineꢀ andꢀ
HMTETAꢀ areꢀ allꢀ displaceableꢀ byꢀ excessꢀ benzylꢀ Grignard,ꢀ andꢀ
theirꢀcomplexesꢀareꢀcatalyticallyꢀcompetentꢀwithꢀanꢀactivityꢀinꢀ
theꢀ orderꢀ HMTETAꢀ <ꢀ sparteineꢀ <ꢀ TMEDAꢀ reflectingꢀ theꢀ
decreasingꢀ chelateꢀ effectꢀ ofꢀ theꢀ ligands.ꢀ Inꢀ theseꢀ casesꢀ theꢀ
catalyticꢀreactionsꢀallꢀturnedꢀblack,ꢀsuggestiveꢀofꢀtheꢀformationꢀ
ofꢀironꢀnanoparticles.ꢀ
1
(
2
(
C
ꢀ
15 2 2
H26Cl FeN :ꢀC,ꢀ49.89;ꢀH,ꢀ7.26;ꢀN,ꢀ7.76.ꢀ
Preparationꢀofꢀcis-[FeCl
2
(HMTETA)],ꢀ8.ꢀAꢀflameꢀdriedꢀSchlenkꢀ
wasꢀ chargedꢀ withꢀ FeCl ꢀ (1.52ꢀg,ꢀ12.0ꢀmmol)ꢀandꢀ THFꢀ(20ꢀml)ꢀ
2
andꢀ theꢀ mixtureꢀ wasꢀ stirredꢀ forꢀ 10ꢀ minsꢀ toꢀ giveꢀ aꢀ grey/pinkꢀ
suspension.ꢀHMTETAꢀwasꢀaddedꢀinꢀoneꢀportionꢀ(3.26ꢀml,ꢀ12.0ꢀ
mmol),ꢀ theꢀ reactionꢀ mixtureꢀ stirredꢀ forꢀ 30ꢀ minsꢀ atꢀ roomꢀ
temperatureꢀ andꢀ thenꢀ heatedꢀ atꢀ refluxꢀ forꢀ 8ꢀ h,ꢀ afterꢀ whichꢀ
timeꢀitꢀwasꢀallowedꢀtoꢀcoolꢀandꢀtheꢀsupernatantꢀremovedꢀviaꢀaꢀ
filterꢀcannula.ꢀTheꢀremainingꢀfineꢀsolidꢀwasꢀwashedꢀwithꢀcoldꢀ
Takenꢀ togetherꢀ theꢀ dataꢀ reportedꢀ hereꢀ provideꢀ furtherꢀ
strongꢀevidenceꢀthatꢀamineꢀligandsꢀareꢀnotꢀcoordinatedꢀtoꢀtheꢀ
ironꢀcentreꢀinꢀtheꢀprimaryꢀcatalyticꢀcycleꢀofꢀKumadaꢀreactionsꢀ
employingꢀ iron-amineꢀ pre-catalysts,ꢀ lendingꢀ supportꢀ toꢀ
variantsꢀofꢀtheꢀcatalyticꢀcycleꢀoutlinedꢀinꢀschemeꢀ3.ꢀ
THFꢀ (3ꢀ xꢀ 3ꢀ ml)ꢀ andꢀ thenꢀ driedꢀ underꢀ vacuumꢀ toꢀ giveꢀ
1
8
whiteꢀsolidꢀ(3.45ꢀg,ꢀ80.5ꢀ%).ꢀ HꢀNMRꢀ(400ꢀMHz,ꢀ25.0ꢀ°C,ꢀTHF)ꢀδꢀ
ꢀ asꢀ aꢀ
1
4
8
1
27.6ꢀ (1471),ꢀ 81.6ꢀ (942),ꢀ 80.5ꢀ (372),ꢀ 70.1ꢀ (854),ꢀ 55.0ꢀ (3314),ꢀ
8.1ꢀ(403),ꢀ-13.6ꢀ(1605),ꢀ-41.1ꢀ(2143).ꢀAnal.ꢀFound:ꢀC,ꢀ40.02;ꢀH,ꢀ
.51;ꢀ N,ꢀ 15.56.ꢀ Calcdꢀ forꢀ C12
2 4
H30Cl FeN :ꢀ C,ꢀ 40.36;ꢀ H,ꢀ 8.47;ꢀ N,ꢀ
Experimentalꢀ
5.64.ꢀCrystalsꢀsuitableꢀforꢀX-rayꢀstructureꢀdeterminationꢀwereꢀ
-
1
ꢀ
grownꢀfromꢀaꢀTHFꢀsolution.ꢀIRꢀ(cm ):ꢀ2972ꢀw,ꢀ2859ꢀm,ꢀ2824ꢀm,ꢀ
General.ꢀ Allꢀ reactionsꢀ wereꢀ carriedꢀ outꢀ underꢀ aꢀ dryꢀ 1468ꢀsh,ꢀ1446ꢀsh,ꢀ1281ꢀsh,ꢀ1174ꢀw,ꢀ1138ꢀw,ꢀ1116ꢀm,ꢀ1066ꢀm,ꢀ
atmosphereꢀofꢀnitrogenꢀusingꢀstandardꢀSchlenkꢀlineꢀandꢀgloveꢀ 1057ꢀm,ꢀ1031ꢀsh,ꢀ1010ꢀm,ꢀ984ꢀsh,ꢀ935ꢀsh,ꢀ897ꢀsh,ꢀ794ꢀm,ꢀ780ꢀ
boxꢀ techniques,ꢀ unlessꢀ otherwiseꢀ specified.ꢀ Anhydrousꢀ sh,ꢀ604ꢀm,ꢀ576ꢀm.ꢀ
solventsꢀwereꢀobtainedꢀfromꢀaꢀGrubbsꢀsolventꢀdryingꢀsystem,ꢀ
ꢀ
degassedꢀ andꢀ storedꢀ overꢀ molecularꢀ sievesꢀ inꢀ aꢀ flameꢀ driedꢀ Preparationꢀofꢀ[FeCl(TMC)]Cl,ꢀ9.ꢀAꢀSchlenkꢀwasꢀchargedꢀwithꢀ
Straussꢀ flask.ꢀ Commercialꢀ reagentsꢀ wereꢀ usedꢀ asꢀ receivedꢀ tetramethylcyclamꢀ(111ꢀmg,ꢀ0.43ꢀmmol)ꢀandꢀanhydrousꢀMeCNꢀ
withoutꢀ furtherꢀ purificationꢀ unlessꢀ otherwiseꢀ specified.ꢀ Theꢀ (5ꢀml).ꢀFeCl ꢀwasꢀaddedꢀinꢀoneꢀportionꢀ(55ꢀmg,ꢀ0.43ꢀmmol)ꢀandꢀ
2
2
ligandꢀ Me EBCꢀ wasꢀ preparedꢀ accordingꢀ toꢀ aꢀ literatureꢀ theꢀreactionꢀmixtureꢀstirredꢀforꢀ30ꢀminsꢀatꢀroomꢀtemperature.ꢀ
1
7 1
method. ꢀ Hꢀ NMRꢀ spectraꢀ wereꢀ recordedꢀ onꢀ aꢀ Jeolꢀ Lambdaꢀ Theꢀreactionꢀmixtureꢀwasꢀthenꢀheatedꢀatꢀ40ꢀ°Cꢀforꢀ1ꢀhꢀresultingꢀ
00,ꢀJeolꢀECPꢀ400,ꢀVarianꢀ400-MR,ꢀorꢀVarianꢀ500ꢀspectrometer.ꢀ inꢀaꢀpaleꢀyellowꢀsolution,ꢀwhichꢀwasꢀallowedꢀtoꢀcool,ꢀfilteredꢀ
3
Thisꢀjournalꢀisꢀ©ꢀTheꢀRoyalꢀSocietyꢀofꢀChemistryꢀ20xxꢀ
J.ꢀName.,ꢀ2013,ꢀ00,ꢀ1-3ꢀ|ꢀ5ꢀ
Pleaseꢀdoꢀnotꢀadjustꢀmarginsꢀ

Ple aDs ae ꢀl dt oo nꢀ n To rt aꢀ and sj ua sc tt ꢀi mo na sr ginsꢀ
Page 6 of 8
ARTICLEꢀ
JournalꢀNameꢀ
1
viaꢀcannulaꢀandꢀleftꢀatꢀ–20ꢀ°Cꢀtoꢀgiveꢀaꢀcropꢀofꢀcrystalsꢀsuitableꢀ gaveꢀ15ꢀasꢀanꢀorangeꢀsolidꢀ(402ꢀmg,ꢀ33.7%).ꢀ HꢀNMRꢀ(400ꢀMHz,ꢀ
View Article Online
forꢀ X-rayꢀ structureꢀ determination.ꢀ Theꢀ crystalsꢀ wereꢀ washedꢀ 25.0ꢀ°C,ꢀTHF)ꢀδꢀ1066.8ꢀ(3823ꢀHz,ꢀ4H),ꢀ121 D. 6O ꢀ I(: 21 10 6. 1 80 3) ,9ꢀ 1/ C0 62 D. 7T 0ꢀ ( 188 92 23 H) ,ꢀ
withꢀ coldꢀ THFꢀ (2ꢀ ml)ꢀ andꢀ driedꢀ underꢀ vacuumꢀ toꢀ giveꢀ theꢀ 99.4ꢀ(763),ꢀ93.3ꢀ(688),ꢀ88.1ꢀ(1897),ꢀ30.4ꢀ(73,ꢀ4H),ꢀ-36.3ꢀ(337,ꢀ
1
productꢀasꢀaꢀcolourlessꢀsolidꢀ(107ꢀmg,ꢀ64.9ꢀ%).ꢀ HꢀNMRꢀ(400ꢀ 4H),ꢀ -61.9ꢀ (76,ꢀ 2H).ꢀ Anal.ꢀ Found:ꢀ C,ꢀ 52.58;ꢀ H,ꢀ 8.02;ꢀ N,ꢀ 8.95.ꢀ
MHz,ꢀ25.0ꢀ°C,ꢀTHF):ꢀδꢀ=ꢀ265.9ꢀ(589),ꢀ103.2ꢀ(952).ꢀAnal.ꢀFound:ꢀ CalcdꢀforꢀC26H46Cl2Fe2N4:ꢀC,ꢀ52.28;ꢀH,ꢀ7.76;ꢀN,ꢀ9.38.ꢀ
C,ꢀ43.99;ꢀH,ꢀ8.19;ꢀN,ꢀ14.24.ꢀCalcdꢀforꢀC14
H
32Cl
2
FeN
.42;ꢀN,ꢀ14.62.ꢀIRꢀ(cm-1):ꢀ2865ꢀbr,ꢀ1472ꢀsh,ꢀ1458ꢀsh,ꢀ1426ꢀw,ꢀ Preparationꢀ ofꢀ [FeBn
115ꢀsh,ꢀ1067ꢀsh,ꢀ999ꢀsh,ꢀ963ꢀsh,ꢀ930ꢀw,ꢀ804ꢀsh,ꢀ727ꢀsh.ꢀ preparationꢀ wasꢀ followed. Toꢀ
addedꢀdiethylꢀetherꢀ(5ꢀml)ꢀandꢀtheꢀmixtureꢀstirred.ꢀToꢀthisꢀwasꢀ
EBC)],ꢀ 10.ꢀ Aꢀ literatureꢀ procedureꢀ addedꢀKCH ꢀ(0.146ꢀg,ꢀ1.12ꢀmmol)ꢀinꢀdiethylꢀetherꢀ(10ꢀml)ꢀ
wasꢀ followed. ꢀ Aꢀ solutionꢀ ofꢀ Me EBCꢀ (1.02ꢀ g,ꢀ 4.0ꢀ mmol)ꢀ inꢀ andꢀtheꢀreactionꢀmixtureꢀwasꢀstirredꢀforꢀ6ꢀhꢀtoꢀgiveꢀaꢀyellowꢀ
anhydrousꢀacetonitrileꢀ(20ꢀml)ꢀwasꢀaddedꢀtoꢀaꢀsuspensionꢀofꢀ solution.ꢀ Thisꢀ wasꢀ filteredꢀ throughꢀ celiteꢀ andꢀ theꢀ solventꢀ
FeCl (py) ]ꢀ (1.14ꢀ g,ꢀ 4.0ꢀ mmol)ꢀ inꢀ anhydrousꢀ acetonitrileꢀ andꢀ removedꢀinꢀvacuoꢀtoꢀyieldꢀ14bꢀasꢀaꢀyellowꢀsolidꢀ(0.151ꢀg,ꢀ57.1ꢀ
theꢀ mixtureꢀ stirredꢀ forꢀ 16ꢀ hꢀ atꢀ roomꢀ temperature.ꢀ (Noteꢀ allꢀ %).ꢀ Theꢀ Hꢀ NMRꢀ spectroscopicꢀ dataꢀ (benzene-d
4
:ꢀC,ꢀ43.88;ꢀH,ꢀ ꢀ
8
1
ꢀ
2
((–)-sparteine)],ꢀ 14b.ꢀ Aꢀ literatureꢀ
1
2ꢀ
7
ꢀ (0.203ꢀ g,ꢀ 0.562ꢀ mmol)ꢀ wasꢀ
Preparationꢀ ofꢀ [FeCl
2
(Me
2
2 6 5
C H
1
3
2
[
2
2
1
6
)ꢀ wereꢀ inꢀ
1
2ꢀ
sourcesꢀ ofꢀ adventitiousꢀ waterꢀ mustꢀ beꢀ avoidedꢀ asꢀ waterꢀ agreementꢀwithꢀreportedꢀvalues, andꢀwereꢀalsoꢀrecordedꢀinꢀ
1
coordinatesꢀ preferentiallyꢀ inꢀ theꢀ ligandꢀ cavityꢀ andꢀ cannotꢀ beꢀ THF.ꢀ HꢀNMRꢀ(400ꢀMHz,ꢀ25.0ꢀ°C,ꢀTHF)ꢀδꢀ932.8ꢀ(2433,ꢀ1H),ꢀ896.2ꢀ
displacedꢀbyꢀtheꢀiron).ꢀTheꢀreactionꢀmixtureꢀwasꢀfilteredꢀandꢀ (2107,ꢀ1H),ꢀ827.8ꢀ(2401,ꢀ1H),ꢀ777.7ꢀ(1626,ꢀ1H),ꢀ350.9ꢀ(343,ꢀ1H),ꢀ
theꢀsolventꢀremovedꢀfromꢀtheꢀfiltrateꢀunderꢀreducedꢀpressureꢀ 341.2ꢀ(371,ꢀ1H),ꢀ218.9ꢀ(315,ꢀ1H),ꢀ147.3ꢀ(958,ꢀ1H),ꢀ136.8ꢀ(794,ꢀ
1
toꢀgiveꢀtheꢀproductꢀasꢀaꢀlightꢀbrownꢀsolidꢀ(1.35ꢀg,ꢀ88.5ꢀ%).ꢀ Hꢀ 1H),ꢀ 129.6ꢀ (1203,ꢀ 1H),ꢀ 120.8ꢀ (215,ꢀ 1H),ꢀ 43.2ꢀ (135,ꢀ 2H),ꢀ 31.7ꢀ
NMRꢀ (400ꢀ MHz,ꢀ 25.0ꢀ °C,ꢀ THF):ꢀ δꢀ =ꢀ 209.5ꢀ (234),ꢀ 192.7ꢀ (234),ꢀ (134,ꢀ 1H),ꢀ 29.9ꢀ (99,ꢀ 2H),ꢀ 28.4ꢀ (168,ꢀ 1H),ꢀ 27.1ꢀ (187,ꢀ 1H),ꢀ 23.1ꢀ
9
0.7ꢀ(411),ꢀ88.0ꢀ(248),ꢀ78.8ꢀ(453),ꢀ69.2ꢀ(248),ꢀ61.6ꢀ(218),ꢀ40.7ꢀ (103,ꢀ2H),ꢀ16.7ꢀ(150,ꢀ1H),ꢀ7.1ꢀ(93,ꢀ1H),ꢀ6.0ꢀ(105,ꢀ1H),ꢀ-3.6ꢀ(177,ꢀ
262),ꢀ 27.3ꢀ (290),ꢀ 26.3ꢀ (276),ꢀ -17.2ꢀ (397),ꢀ -106.6ꢀ (893).ꢀ Anal.ꢀ 1H),ꢀ -11.3ꢀ (134,ꢀ 1H),ꢀ -14.6ꢀ (122,ꢀ 1H),ꢀ -21.4ꢀ (311,ꢀ 1H),ꢀ -21.8ꢀ
(
Found:ꢀC,ꢀ45.36;ꢀH,ꢀ8.25;ꢀN,ꢀ15.14.ꢀCalcdꢀforꢀC14
H
5.11;ꢀ H,ꢀ 7.93;ꢀ N,ꢀ 14.70.ꢀ Crystalsꢀ suitableꢀ forꢀ X-rayꢀ structureꢀ 1H),ꢀ-41.8ꢀ(649,ꢀ1H),ꢀ-48.3ꢀ(277,ꢀ1H),ꢀ-56.7ꢀ(87,ꢀ1H),ꢀ-72.9ꢀ(104,ꢀ
30Cl
2
FeN
4
:ꢀC,ꢀ (161,ꢀ 1H),ꢀ -33.3ꢀ (137,ꢀ 1H),ꢀ -38.3ꢀ (575,ꢀ 1H),ꢀ -41.0ꢀ (165,ꢀ
2H),ꢀ-86.0ꢀ(1139,ꢀ1H),ꢀ-148.1ꢀ(1208,ꢀ1H).ꢀ
4
determinationꢀwereꢀgrownꢀfromꢀaꢀcooledꢀTHFꢀsolution.ꢀ
ꢀ
Cross-couplingꢀofꢀ4-tolylMgBrꢀwithꢀcyclohexylꢀbromide:ꢀTableꢀ
Acknowledgementsꢀ
1
,ꢀ conditionsꢀ A.ꢀ Cyclohexylꢀ bromideꢀ (123ꢀ μl,ꢀ 1.0ꢀ mmol),ꢀ theꢀ
appropriateꢀironꢀcomplexꢀ(0.05ꢀmmol)ꢀandꢀwhereꢀappropriate,ꢀ
TMEDAꢀ(300ꢀμl,ꢀ2.0ꢀmmol)ꢀwereꢀstirredꢀforꢀ3ꢀminutesꢀinꢀTHFꢀ
Weꢀ thankꢀ theꢀ EPSRCꢀ forꢀ aꢀ PhDꢀ studentshipꢀ (JN)ꢀ andꢀ
postdoctoralꢀ supportꢀ (PBBꢀ andꢀ DE,ꢀ grantꢀ numberꢀ
2.0ꢀ ml)ꢀ heldꢀ atꢀ 0ꢀ °C.ꢀ 4-TolylMgBrꢀ (1.2ꢀ mmol)ꢀ wasꢀ addedꢀ
EP/K012258/1).ꢀꢀ
(
dropwiseꢀwithꢀstirringꢀoverꢀ30ꢀminsꢀusingꢀaꢀsyringeꢀpumpꢀandꢀ
theꢀreactionꢀmixtureꢀwasꢀstirredꢀforꢀaꢀfurtherꢀ30ꢀminsꢀatꢀ0ꢀ°C.ꢀ
TheꢀreactionꢀwasꢀquenchedꢀbyꢀadditionꢀofꢀH
organicꢀ productsꢀ extractedꢀ withꢀ CH Cl ꢀ (3ꢀ xꢀ 10ꢀ ml).ꢀ 1,3,5-
2
Oꢀ(5ꢀml)ꢀandꢀtheꢀ Notesꢀandꢀreferencesꢀ
2
2
1
(a)ꢀMetal-CatalyzedꢀCross-CouplingꢀReactions,ꢀSecondꢀEditionꢀ
eds.ꢀ A.ꢀ deꢀ Meijereꢀ andꢀ F.ꢀ Diederic)ꢀ 2008,ꢀ Wiley-VCH.ꢀ (b)ꢀ
Trimethoxybenzeneꢀ (168ꢀ mg,ꢀ 1.0ꢀ mmol)ꢀ wasꢀ addedꢀ asꢀ anꢀ
internalꢀstandardꢀandꢀtheꢀconversionꢀtoꢀcross-coupledꢀproductꢀ
1
wasꢀ determinedꢀ byꢀ Hꢀ NMRꢀ spectroscopy.ꢀ Conditionsꢀ B.ꢀ
(
Handbookꢀ ofꢀ Organopalladiumꢀ Chemistryꢀ forꢀ Organicꢀ
Synthesisꢀ(ed.ꢀE.ꢀNegishi)ꢀ2002,ꢀWiley.ꢀ
2
3
M.ꢀ
Albrecht,ꢀ
R.ꢀ
Bedfordꢀ
andꢀ
B.ꢀ
Cyclohexylꢀ bromideꢀ (123ꢀ μl,ꢀ 1.0ꢀ mmol),ꢀ theꢀ relevantꢀ ironꢀ
complexꢀ (0.05ꢀ mmol)ꢀ andꢀ whereꢀ appropriate,ꢀ TMEDAꢀ (15ꢀ μl,ꢀ
Plietker,ꢀOrganometallics,ꢀ2014,ꢀ33,ꢀ5619.ꢀ
Itꢀ shouldꢀ beꢀ notedꢀ thatꢀ iron-catalysedꢀ cross-couplingsꢀ pre-
dateꢀ analogousꢀ palladium-catalysedꢀ processes.ꢀ Forꢀ seminalꢀ
examplesꢀ see:ꢀ (a)ꢀ G.ꢀ Vavonꢀ andꢀ P.ꢀ Mottez,ꢀ C.ꢀ R.ꢀ Hebd.ꢀ
SeancesꢀAcad.ꢀSci.,ꢀ1944,ꢀ218,ꢀ557;ꢀ(b)ꢀW.ꢀC.ꢀPercival,ꢀR.ꢀB.ꢀ
WagnerꢀandꢀN.ꢀC.ꢀCook,ꢀJ.ꢀAm.ꢀChem.ꢀSoc.,ꢀ1953,ꢀ75,ꢀ3731;ꢀ
0
2
.1ꢀmmol)ꢀwereꢀstirredꢀforꢀ3ꢀminutesꢀinꢀEt Oꢀ(3.0ꢀml)ꢀatꢀroomꢀ
temperature.ꢀ 4-TolylMgBrꢀ (2.0ꢀ mmol)ꢀ wasꢀ addedꢀ inꢀ oneꢀ
portionꢀandꢀtheꢀreactionꢀmixtureꢀheatedꢀatꢀrefluxꢀtemperatureꢀ
forꢀ 1ꢀ h.ꢀ Workupꢀ andꢀ determinationꢀ ofꢀ conversionꢀ toꢀ cross-
coupledꢀproductꢀasꢀabove.ꢀꢀ
(
1
c)ꢀM.ꢀTamuraꢀandꢀJ.ꢀK.ꢀKochi,ꢀJ.ꢀAm.ꢀChem.ꢀSoc.,ꢀ1971,ꢀ93,ꢀ
487;ꢀ(d)ꢀM.ꢀTamuraꢀandꢀJ.ꢀKochi,ꢀSynthesis,ꢀ1971,ꢀ303;ꢀ(e)ꢀS.ꢀ
ꢀ
M.ꢀNeumannꢀandꢀJ.ꢀK.ꢀKochi,ꢀJ.ꢀOrg.ꢀChem.,ꢀ1975,ꢀ40,ꢀ599;ꢀ(f)ꢀ
R.ꢀS.ꢀSmithꢀandꢀJ.ꢀK.ꢀKochi,ꢀJ.ꢀOrg.ꢀChem.,ꢀ1976,ꢀ41,ꢀ502.ꢀꢀ
Recentꢀreviews:ꢀ(a)ꢀIngmarꢀBauerꢀandꢀHans-JoachimꢀKnölker,ꢀ
Chem.ꢀ Rev.ꢀ 2015,ꢀ 115,ꢀ 3170;ꢀ (b)ꢀ R.ꢀ B.ꢀ Bedfordꢀ andꢀ P.ꢀ B.ꢀ
Brenner,ꢀ Top.ꢀ Organomet.ꢀ Chem.,ꢀ 2015,ꢀ 50,ꢀ 19;ꢀ (c)ꢀ E.ꢀ
Nakamura,ꢀT.ꢀHatakeyama,ꢀS.ꢀIto,ꢀK.ꢀIshizuka,ꢀL.ꢀIliesꢀandꢀM.ꢀ
Nakamura,ꢀOrg.ꢀReact.ꢀ2014,ꢀ83,ꢀ1.ꢀꢀꢀ
NMRꢀstudiesꢀofꢀtheꢀreactionꢀofꢀiron-amineꢀchelateꢀcomplexesꢀ
withꢀ BnMgClꢀ (Figuresꢀ 4ꢀ –ꢀ 7).ꢀ Theꢀ appropriateꢀ iron-amineꢀ
complexꢀ (0.5ꢀ mmol)ꢀ wasꢀ dissolvedꢀ inꢀ THFꢀ (2ꢀ ml),ꢀ BnMgClꢀ
4
(
0.84Mꢀ inꢀ THF,ꢀ specifiedꢀ amount)ꢀ wasꢀ addedꢀ atꢀ roomꢀ
temperature,ꢀ theꢀ reactionꢀ mixtureꢀ stirredꢀ forꢀ 10ꢀ mins,ꢀ aꢀ
1
sampleꢀwasꢀremovedꢀandꢀtheꢀ HꢀNMRꢀwasꢀrecorded.ꢀꢀ
5
6
7
M.ꢀ Nakamura,ꢀ K.ꢀ Matsuo,ꢀ S.ꢀ Itoꢀ andꢀ E.ꢀ Nakamura,ꢀ J.ꢀ Am.ꢀ
Chem.ꢀSoc.,ꢀ2004,ꢀ126,ꢀ3686.ꢀ
R.ꢀB.ꢀBedford,ꢀD.ꢀW.ꢀBruce,ꢀR.ꢀM.ꢀFrostꢀandꢀM.ꢀHird,ꢀChem.ꢀ
Commun.ꢀ2005,ꢀ4161.ꢀ
G.ꢀ Cahiez,ꢀ V.ꢀ Habiak,ꢀ C.ꢀ Duplaisꢀ andꢀ A.ꢀ Moyeux,ꢀ Angew.ꢀ
Chem.,ꢀInt.ꢀEd.ꢀ2007,ꢀ46,ꢀ4364.ꢀ
ꢀ
Preparationꢀofꢀ[FeClBn(TMEDA)],ꢀ15.ꢀComplexꢀ
mmol)ꢀ wasꢀ dissolvedꢀ inꢀ THFꢀ (5.0ꢀ ml),ꢀ BnMgClꢀ addedꢀ (2.0ꢀ ml,ꢀ
.0ꢀMꢀinꢀTHF,ꢀ4.0ꢀmmol)ꢀandꢀtheꢀreactionꢀmixtureꢀstirredꢀforꢀ10ꢀ
minꢀtoꢀgiveꢀanꢀorangeꢀsolution.ꢀCoolingꢀtheꢀsolutionꢀatꢀ-20ꢀ°Cꢀ
6ꢀ(0.972ꢀg,ꢀ2.0ꢀ
2
6
ꢀ|ꢀJ.ꢀName.,ꢀ2012,ꢀ00,ꢀ1-3ꢀ
Thisꢀjournalꢀisꢀ©ꢀTheꢀRoyalꢀSocietyꢀofꢀChemistryꢀ20xxꢀ
Pleaseꢀdoꢀnotꢀadjustꢀmarginsꢀ

Page 7 of 8
Ple aDs ae ꢀl dt oo nꢀ n To rt aꢀ and sj ua sc tt ꢀi mo na sr ginsꢀ
JournalꢀNameꢀ
ꢀARTICLEꢀ
8
9
D.ꢀ Noda,ꢀ Y.ꢀ Sunada,ꢀ T.ꢀ Hatakeyama,ꢀ M.ꢀ Nakamuraꢀ andꢀ H.ꢀ
Nagashima,ꢀJ.ꢀAm.ꢀChem.ꢀSoc.ꢀ2009,ꢀ131,ꢀ6078.ꢀ
R.ꢀB.ꢀBedford,ꢀP.ꢀB.ꢀBrenner,ꢀE.ꢀCarter,ꢀP.ꢀM.ꢀCogswell,ꢀM.ꢀF.ꢀ
Haddow,ꢀ J.ꢀ N.ꢀ Harvey,ꢀ D.ꢀ M.ꢀ Murphy,ꢀ J.ꢀ Nunnꢀ andꢀ C.ꢀ H.ꢀ
Woodall,ꢀAngew.ꢀChem.,ꢀInt.ꢀEd.,ꢀ2014,ꢀ53,ꢀ1804.ꢀ
View Article Online
DOI: 10.1039/C6DT01823H
1
1
0 R.ꢀB.ꢀBedford,ꢀAcc.ꢀChem.ꢀRes.ꢀ2015,ꢀ48,ꢀ1485.ꢀ
1 S.ꢀC.ꢀDavies,ꢀD.ꢀL.ꢀHughes,ꢀG.ꢀJ.ꢀLeigh,ꢀJ.ꢀR.ꢀSandersꢀandꢀJ.ꢀS.ꢀ
deꢀSouza,ꢀJ.ꢀChem.ꢀSoc.,ꢀDaltonꢀTrans.,ꢀ1997,ꢀ1981.ꢀ
1
1
2 S.ꢀC.ꢀBart,ꢀE.ꢀJ.ꢀHawrelak,ꢀA.ꢀK.ꢀSchmisseur,ꢀE.ꢀLobkovskyꢀandꢀ
P.ꢀJ.ꢀChirik,ꢀOrganometallics,ꢀ2004,ꢀ23,ꢀ237.ꢀ
3 T.ꢀJ.ꢀHubin,ꢀJ.ꢀM.ꢀMcCormick,ꢀS.ꢀR.ꢀCollinson,ꢀM.ꢀBuchalova,ꢀC.ꢀ
M.ꢀPerkins,ꢀN.ꢀW.ꢀAlcock,ꢀP.ꢀK.ꢀKahol,ꢀA.ꢀRaghunathanꢀandꢀD.ꢀ
H.ꢀBusch,ꢀJ.ꢀAm.ꢀChem.ꢀSoc.,ꢀ2000,ꢀ122,ꢀ2512.ꢀ
1
1
4 R.ꢀ B.ꢀ Bedford,ꢀ M.ꢀ Betham,ꢀ D.ꢀ W.ꢀ Bruce,ꢀ S.ꢀ A.ꢀ Davis,ꢀ R.ꢀ M.ꢀ
Frost,ꢀM.ꢀHird,ꢀChem.ꢀCommun.,ꢀ2006,ꢀ1398.ꢀ
5 R.ꢀ B.ꢀ Bedford,ꢀ P.ꢀ B.ꢀ Brenner,ꢀ E.ꢀ Carter,ꢀ T.ꢀ W.ꢀ Carvell,ꢀ P.ꢀ M.ꢀ
Cogswell,ꢀ T.ꢀ Gallagher,ꢀ J.ꢀ N.ꢀ Harvey,ꢀ D.ꢀ M.ꢀ Murphy,ꢀ E.ꢀ C.ꢀ
Neeve,ꢀJ.ꢀNunnꢀandꢀD.ꢀR.ꢀPye,ꢀChem. Eur.ꢀJ.ꢀ2014,ꢀ20,ꢀ7935.ꢀ
6 D.ꢀH.ꢀHillꢀandꢀA.ꢀSen,ꢀJ.ꢀAm.ꢀChem.ꢀSoc.,ꢀ1988,ꢀ110,ꢀ1650.ꢀ
7 E.ꢀ H.ꢀ Wong,ꢀ G.ꢀ R.ꢀ Weisman,ꢀ D.ꢀ C.ꢀ Hill,ꢀ D.ꢀ P.ꢀ Reed,ꢀ M.ꢀ E.ꢀ
Rogers,ꢀJ.ꢀS.ꢀCondon,ꢀM.ꢀA.ꢀFagan,ꢀJ.ꢀC.ꢀCalabrese,ꢀK.ꢀLam,ꢀI.ꢀ
A.ꢀGuzeiꢀandꢀA.ꢀL.ꢀRheingold,ꢀJ.ꢀAm.ꢀChem.ꢀSoc.,ꢀ2000,ꢀ122,ꢀ
1
1
1
0561.ꢀ
ꢀ
Thisꢀjournalꢀisꢀ©ꢀTheꢀRoyalꢀSocietyꢀofꢀChemistryꢀ20xxꢀ
J.ꢀName.,ꢀ2013,ꢀ00,ꢀ1-3ꢀ|ꢀ7ꢀ
Pleaseꢀdoꢀnotꢀadjustꢀmarginsꢀ

Dalton Transactions
Page 8 of 8
View Article Online
DOI: 10.1039/C6DT01823H
Abstract:
The performance of Fe-amine pre-catalysts in a representative Kumada reaction is inversely
proportional to the lability of the chelate ligand.